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Essential hypertension

Highlights
Summary Overview

Basics
Definition Epidemiology Aetiology Pathophysiology

Prevention
Primary Screening Secondary

Diagnosis
History & examination Tests Differential Step-by-step Criteria Guidelines Case history

Treatment
Details Step-by-step Emerging Guidelines Evidence

Follow Up
Recommendations Complications Prognosis

Resources
References Online resources Patient leaflets Credits Email Print Feedback Share Add to Portfolio Bookmark Add notes

History & exam


Key factors
presence of risk factors BP >140/90 mmHg retinopathy

Other diagnostic factors


headache visual changes dyspnoea chest pain sensory or motor deficit

History & exam details

Diagnostic tests
1st tests to order
ECG fasting metabolic panel with estimated GFR fasting lipid panel Hb urinalysis with microalbumin

Tests to consider
echocardiogram carotid Dopplers plasma renin activity (PRA) plasma aldosterone renal duplex ultrasound/MRA renal arteries 24-hour urine phaeochromocytoma screen 24-hour urine free cortisol TSH ambulatory BP monitor Diagnostic tests details

Treatment details
Ongoing
no comorbidity (other than osteoporosis): non-pregnant o o o o stage 1 HTN (BP 140 to 159/90 to 99 mmHg) diuretic monotherapy + lifestyle modification ACE inhibitor/angiotensin-II receptor blocker monotherapy + lifestyle modification beta-blocker monotherapy + lifestyle modification dihydropyridine CCB monotherapy + lifestyle modification stage 1 not at goal with monotherapy or stage 2 (BP 160/100 mmHg)

o o o o o

thiazide + ACE inhibitor/angiotensin-II receptor blocker + lifestyle modification ACE inhibitor/angiotensin-II receptor blocker + dihydropyridine CCB + lifestyle modification ACE inhibitor/angiotensin-II receptor blocker + beta-blocker + lifestyle modification thiazide + beta-blocker + lifestyle modification beta-blocker + dihydropyridine CCB + lifestyle modification concomitant CAD without CHF: non-pregnant

o o o o o o

stage 1 HTN (BP 140 to 159/90 to 99 mmHg) beta-blocker monotherapy + lifestyle modification dihydropyridine CCB monotherapy + lifestyle modification stage 1 not at goal with monotherapy or stage 2 (BP 160/100 mmHg) beta-blocker + dihydropyridine CCB + lifestyle modification beta-blocker + ACE inhibitor/angiotensin-II receptor blocker + lifestyle modification thiazide + beta-blocker + lifestyle modification ACE inhibitor/angiotensin-II receptor blocker + thiazide + lifestyle modification concomitant CHF with ejection fraction less than 55%: non-pregnant

o o o

NYHA class I or II ACE inhibitor/angiotensin-II receptor blocker + beta-blocker + lifestyle modification non-aldosterone-blocking diuretics NYHA class III or IV ACE inhibitor/angiotensin-II receptor blocker + beta-blocker + aldosterone antagonist + lifestyle modification

o o

non-aldosterone-blocking diuretics substitution or addition of isosorbide dinitrate/hydralazine concomitant LVH without CAD: non-pregnant

angiotensin-II receptor blocker/ACE inhibitor monotherapy + lifestyle modification concomitant diabetes or chronic renal disease without cardiovascular disease: non-pregnant

o o o o o

stage 1 HTN (BP 140 to 159/90 to 99 mmHg) ACE inhibitor/angiotensin-II receptor blocker monotherapy + lifestyle modification dihydropyridine CCB monotherapy + lifestyle modification thiazide monotherapy + lifestyle modification beta-blocker monotherapy + lifestyle modification stage 1 not at goal with monotherapy or stage 2 (BP 160/100 mmHg) ACE inhibitor/angiotensin-II receptor blocker + thiazide + lifestyle modification

o o

ACE inhibitor/angiotensin-II receptor blocker + dihydropyridine CCB + lifestyle modification ACE inhibitor/angiotensin-II receptor blocker + beta-blocker + lifestyle modification concomitant atrial fibrillation without other comorbidity: non-pregnant

beta-blocker monotherapy + lifestyle modification non-dihydropyridine CCB + lifestyle modification concomitant benign prostatic hypertrophy without other comorbidity

alpha-blocker + lifestyle modification concomitant Raynaud's disease, PVD, coronary, or spasm without other comorbidity: non-pregnant

dihydropyridine CCB + lifestyle modification refractory/resistant to optimised triple therapy at any stage: non-pregnant without CHF

ACE inhibitor/angiotensin-II receptor blocker + thiazide + CCB + beta-blocker + lifestyle modification hydralazine added to 3 agents clonidine added to 3 agents alpha-blocker added to 3 agents minoxidil added to 3 agents aliskiren added to 3 agents pregnant

methyldopa + lifestyle modification labetalol + lifestyle modification Treatment details

Summary
Defined as BP greater than 140/90 mmHg. Typically diagnosed by screening of an asymptomatic individual. Treatment of uncontrolled HTN reduces the risks of mortality and of cardiac, vascular, renal, or cerebrovascular complications. Lifestyle changes are recommended for all patients: weight loss, exercise, decreased sodium intake, and moderation of alcohol consumption. Choice of drug therapy is often driven by considerations related to comorbid disease, but achievement of BP goal supersedes choice of therapeutic agent(s).

Other related conditions


Assessment of hypertension Overview of acute coronary syndrome Overview of stroke

Chronic congestive heart failure Aortic dissection Abdominal aortic aneurysm Metabolic syndrome Overview of diabetes Obesity in adults Chronic renal failure Peripheral vascular disease Assessment of dementia Phaeochromocytoma Primary aldosteronism

Definition
Essential HTN is defined as BP greater than 140/90 mmHg. [1] [2] [3] The main goal of treatment is to decrease the risk of mortality and of cardiovascular and renal morbidity. [4] BP goal should be less than 130/80 mmHg in patients with renal disease, and less than 140/90 mmHg in all other patients. Regarding patients with concomitant diabetes mellitus, there is good-quality evidence that very intensive BP lowering (targeting a systolic pressure <120 mmHg, as compared with targeting <140 mmHg) does not lessen risk (composite outcome: non-fatal MI, non-fatal stroke, or death from cardiovascular cause) and may increase risk of adverse events. [5] Pre-HTN is defined as systolic BP 120 to 139 mmHg and diastolic BP 80 to 89 mmHg. [1] In essential HTN, a secondary cause has not been identified.

Epidemiology
Worldwide, it is estimated that 1 billion people are hypertensive, accounting for an estimated 7.1 million deaths per year. [6] It is becoming an increasingly common problem because of increased longevity and the prevalence of contributing factors such as obesity, physical inactivity, and unhealthy diet. [7] [8] The prevalence in many developing countries, particlularly urban societies, is already as high as those seen in developed countries. [9] The prevalence of essential HTN in the US was estimated to be 65 million people in 2000, compared with 50 million people in 1990. [10] Based on National Health and Nutrition Examination Surveys (NHANES) data, prevalence is highest in black women, who also develop HTN at a younger age than other groups. [11] Prevalence is higher in white Americans than in

Mexican Americans. [12] The incidence increases with age in people of all ancestries and both sexes. Prevalence is higher in men than in women before 60 years of age, but equal after this age. [4] The lifetime risk is 90% for men and women who were normotensive at 55 years of age and survive to 80 years. [13]

Aetiology
A multifactorial and heterogeneous aetiology of essential HTN has been proposed. [14]However, some initiating factors may be dampened as the hypertensive state progresses. [15]The following factors have been shown to disrupt the delicate balance of cardiac output and resistance, ultimately resulting in HTN:
Disturbance of auto-regulation (reflex and persistenly increasing vascular resistance to match an increased cardiac output) [16] Excess sodium intake through a variety of mechanisms [17] [18] Renal sodium retention [19] [20] [21] [22] Dysregulation of the renin-angiotensin-aldosterone axis, with elevated plasma renin activity (PRA) [23] Increased sympathetic drive [24] Increased peripheral resistance [25] Endothelial dysfunction [26] Cell membrane transporter perturbations [27] Insulin resistance/hyperinsulinaemia. [28]

Pathophysiology
BP, the product of cardiac output and peripheral vascular resistance, is affected by preload, contractility, vessel hypertrophy, and peripheral constriction. The pathology associated with, and the perpetuation of, the hypertensive state involves structural changes, remodelling, and hypertrophy in resistance arterioles. [15] These changes have also been associated with the early and progressive development of small vessel atherosclerosis, which is probably the cause of end-organ damage seen in advanced HTN. This occurs through a complex series of interrelated processes including thrombosis, endothelial injury and dysfunction, the inflammatory cascade, oxidative stress, and autonomic dysregulation in the setting of genetic predisposition. [29] Trials have demonstrated the importance of systolic BP in the pathophysiology of HTN and its associated complications, which differs from older conventional thinking. [30] The rise in systolic BP continues throughout life, in contrast to diastolic BP, which increases until approximately 50 years

of age, tends to level off over the following decade, and may stabilise or decline subsequently.

Primary prevention
The lifetime risk for development of HTN is high. Efforts should be made to minimise risk factors, especially in patients with pre-HTN (defined as 120 to 139/80 to 89 mmHg); these patients should be aggressively counselled to effect lifestyle modifications so as to reduce their risk of developing HTN. Population-based approaches to prevent HTN have been proposed: the American Public Health Association has advocated a 50% reduction in the sodium content of all foods. [41] Although sodium reduction has a modest effect on BP lowering, the population effect on the huge number of at-risk people would potentially have significant consequences for cardiovascular morbidity and mortality.

Screening
The vast majority of hypertensive patients will be detected during an asymptomatic screening during some contact with the medical system. Patients aged over 18 years who are asymptomatic (no evidence of endorgan damage and normal initial BP) should be screened every 2 years. [1] [48] Asymptomatic patients with pre-HTN should be screened annually for the development of HTN. [1] These screening guidelines are often exceeded, as BP measurement is standard for each encounter in many practice settings. Elevated readings should always be confirmed on a second visit prior to diagnosing HTN.

Secondary prevention
Aggressive lifestyle modifications should be initiated in patients with pre-HTN (BP 120 to 139/80 to 89 mmHg) to delay or prevent the onset of overt HTN. Furthermore, other cardiovascular risk parameters should be aggressively managed. For example, LDL-cholesterol should be maintained at less than 100 mg/dL (2.59 mmol/L) in people with type 2 diabetes. Accordingly, patients with pre-HTN should be evaluated for occult cardiovascular risk by screening for diabetes or dyslipidaemia with fasting blood sugar and lipid levels.

History & examination


Key diagnostic factorshide all
presence of risk factors (common)

Key risk factors include age >65 years, moderate/high alcohol intake, lack of exercise, FHx of HTN or CAD, obesity, metabolic syndrome, diabetes mellitus, hyperuricaemia, black ancestry, and obstructive sleep apnoea.

BP >140/90 mmHg (common)

Anaeroid, mercury, or electronic cuff. Equipment needs calibration. Diagnosis is made at lower cut-off of 130/80 mmHg for high-risk patients (diabetes or renal disease).

retinopathy (common)

Retinal vascular changes are seen commonly in longstanding HTN.

Other diagnostic factorshide all


headache (uncommon) Rarely a presenting symptom, unless HTN is acute or in setting of hypertensive urgency. visual changes (uncommon) Decreased visual acuity or floaters, papilloedema (rare). dyspnoea (uncommon)

Suggests possible CHF or CAD. Dyspnoea may be an anginal equivalent, particularly if a patient is diabetic.

chest pain (uncommon) Suggests CAD. sensory or motor deficit (uncommon)

Risk

Suggests cerebrovascular disease. factorshide all

Strong obesity

Data from the Nurses' Health Study showed that a gain of 5 kg above weight at 18 years of age was associated with 60% higher risk of development of HTN in middle age. [31] A 4.5 mmHg increase in BP has been associated with each 4.5 kg (10 lb) gain in weight. [32]

It has been postulated that the link between obesity and HTN is driven by increased circulating volume, leading to increased cardiac output and persistently elevated peripheral vascular resistance. [28]

Obesity is associated with the metabolic syndrome, insulin resistance, and type 2 diabetes. Bariatric treatment of morbid obesity can reduce or eliminate risk factors for cardiovascular disease, with an effect on hypertension, diabetes, and dyslipidaemia. [33][34]

aerobic exercise less than 3 times/week

Patients with low level of fitness had a 52% greater relative risk of HTN at 12-year follow-up compared with those with high levels of fitness. [35]

moderate/high alcohol intake

Chronic alcohol consumption of greater than 1.5 drinks per day has been shown to be associated with an increased risk of developing HTN in young women. [37]The risk increases with more than 5 drinks per week in women and more than 7 drinks per week in men.

Acute alcohol consumption, in contrast, is associated with vasomotor relaxation. metabolic syndrome

Abdominal obesity has been specifically associated with an increased risk of HTN, as compared with generalised obesity. [38]

Insulin resistance and hyperinsulinaemia are thought to contribute to the development of HTN through a variety of inflammatory mechanisms. [15]

diabetes mellitus

Hyperglycaemia, hyperinsulinaemia, and insulin resistance lead to endothelial damage and oxidative stress, and are independently associated with the development of HTN. [39]

hyperuricaemia

A growing body of evidence has shown an association between elevated uric acid levels and HTN, as well as cardiovascular events. The proposed causative mechanism involves renal afferent thickening and constriction. [40]

black ancestry Highest incidence of HTN is seen in black non-Hispanic people, at all age levels. [4] age >65 years Incidence of HTN increases with age in people of all ancestries and both sexes. [4] FHx HTN or CAD sleep apnoea

Studies have shown around 50% of patients with sleep apnoea have essential HTN. [1]

Weak sodium intake greater than 2.4 g/day

Individuals show a varied tolerance for sodium intake, and reduced sodium intake has modest effect on BP lowering. [17] [18]

low fruit and vegetable intake

Modest reduction in BP with 4 to 6 servings of fruits and vegetables coupled with lower sodium and fat intake (Dietary Approaches to Stop Hypertension [DASH] diet).[36]

dyslipidaemia

Risk of HTN is increased in setting of the metabolic syndrome.

Diagnostic tests
1st tests to orderhide all
Test

ECG Normal result does not rule out CAD.

fasting metabolic panel with estimated GFR Risk of HTN is increased if there are features of the metabolic syndrome. Unprovoked hypokalaemia suggests hyperaldosteronism. GFR is calculated according to the Modification of Diet in Renal Disease (MDRD) formula [44] [National Kidney Foundaton: GFR calculator] (external link) fasting lipid panel Risk of HTN is increased in setting of the metabolic syndrome. Hb Anaemia accompanies chronic renal failure. Polycythaemia may be seen with phaeochromocytoma. urinalysis with microalbumin Suggests end-organ damage.

Tests to considerhide all


Test

echocardiogram Not routinely recommended, but suggested in patients with other cardiovascular risk factors. Quantifies left ventricular mass (LVM) and geometric LVH patterns, which have prognostic implications (i.e., increased risk of mortality and cardiovascular events in patients with increased LVM and abnormal geometric LVH). [45] [46] carotid Dopplers

Not routinely recommended, but suggested in patients with other cardiovascular risk factors. Quantifies carotid IM values). [47] plasma renin activity (PRA) Indicated when unprovoked hypokalaemia present. plasma aldosterone Indicated when unprovoked hypokalaemia present.

and plaques, which have prognostic implications (i.e., increased cardiovascular events associated with higher IM

renal duplex ultrasound/MRA renal arteries Young patients (age <40 years) with severe HTN or renal artery bruits.

Ultrasound provides haemodynamical information and magnetic resonance angiogram (MRA) provides anatomic information, in lieu of renal angiogram. 24-hour urine phaeochromocytoma screen Indicated with symptoms/signs of catecholamine excess. 24-hour urine free cortisol Indicated when stigmata of Cushing's disease present. TSH Indicated if signs/symptoms of hypo- or hyperthyroidism. ambulatory BP monitor Useful in patients with suspected white-coat HTN, apparent drug resistance, or episodic HTN.

Differential diagnosis
Condition Drug-induced Differentiating signs/symptoms Differentiating tests

There may be signs of acute intoxication, withdrawal, or cravings with cocaine/sympathomimeti cs use.

Drug toxicology screen may detect an illicit substance. Hypokalaemia if excessive liquorice.

History of treatment with or ingestion of nonsteroidal antiinflammatory drugs, OCPs, sympathomimetics, herbal medications (e.g., black cohosh, capsicum, ma huang), or liquorice.

Chronic renal failure

There may be pruritus, halitosis, oedema, or change in urine output.

High serum creatinine. Chronic anaemia may be seen.

Renal ultrasound may identify sclerotic or polycystic kidn

Aortic coarctation

Differential BP in upper and lower extremities. Absent femoral pulses.

CT, angiogram, or MRI confirms diagnosis.

Renal artery stenosis

Typically younger patients with difficult-tocontrol HTN.

Renal duplex ultrasound or magnetic resonance angiog arteries confirms diagnosis.

Renal artery bruits may be present.

Sleep apnoea, obstructive

Typically obese patients with daytime somnolence, snoring, or choking during sleep.

Polysomnography shows nocturnal oxygen desaturation

Hyperaldosteronism

There may be weakness or paraesthesiae.

Unprovoked hypokalaemia. Plasma aldosterone high. Plasma renin low. Failure to suppress aldosterone with salt loading.

Hypothyroidism

Dry skin, cold intolerance, weight gain, sluggishness, and goitre.

TSH elevated in primary hypothyroidism.

Hyperthyroidism

Heat intolerance, weight loss, hyperphagia, palpitations.

TSH suppressed and levels of free thyroid hormones ele

Hyperparathyroidism

There are often no differentiating symptoms; however, renal colic, abdominal pain, or bone fracture may occur.

Hypercalcaemia, with elevated or inappropriately norma

Cushing's syndrome

Classic symptoms and signs include weight gain, moon face, dorsicocervical fat pad, abdominal striae, and easy bruisability.

Abnormal dexamethasone suppression, 24-hour urine fr night salivary cortisol.

Phaeochromocytoma

Paroxysms of HTN, flushing, and headache.

24-hour urine screen shows elevated vanillylmandelic a and/or catecholamines.

Acromegaly

Acral (hand/foot/jaw) enlargement.

Elevated insulin-like growth factor-1 (IGF-1). Elevated s level, not suppressed by glucose load.

Collagen vascular disease

Signs/symptoms of systemic lupus erythematosus (SLE), rheumatoid arthritis, sclerodactly, or Hx vasculitis.

Elevated ESR, abnormal complement levels, positive an

ribonucleoprotein (anti-RNP), anti-Smith antibodies, pos

Step-by-step diagnostic approach


Most patients diagnosed with HTN are asymptomatic; therefore, screening is essential. Patients are usually evaluated through history, physical examination, and routine laboratory tests. The 3 objectives are to:
Assess risk factors Reveal identifiable causes Detect target-organ damage, including evidence of cardiovascular disease.

Clinical evaluation
History may elicit family history of HTN or CAD risk factors. It is important to assess overall cardiac risk burden. [2] The age of onset may be of value when considering aetiology, as the proportion of secondary causes diminishes with increasing age. Patients at increased risk for essential HTN include those over 65 years of age, or with diabetes, or of black ancestry. Excess alcohol intake or lack of exercise should be documented. A thorough medication history should be taken including screening for use of OCPs, nonsteroidal anti-inflammatory drugs (NSAIDs), sympathomimetics, or herbal medications. Most patients are asymptomatic, but clinical indications of hyperthyroidism, hypothyroidism or catecholamine excess (e.g., tachycardia, weight loss, sweating, or palpitations), or end-organ damage (e.g., shortness of breath, chest pain, or sensory/motor deficits) should be sought. Headache or visual changes are unusual. The physical examination should include: [1]
BP: the patient should be seated quietly for at least 5 minutes, with feet on the floor and arm supported at heart level. Caffeine, smoking, and exercise should be avoided for 30 minutes prior to examination. An appropriately sized cuff should be used. The bladder should be 80% of the length of the upper arm, and the width of the bladder should be at least 40% of the circumference of the upper arm. Two measurements should be made and the average recorded. [1] Verification should be obtained in the contralateral arm. Pre-HTN is a reading of 120 to 139/80 to 89 mmHg. HTN is above 140/90 mmHg in adults, or above 130/80 mmHg in patients with renal disease Examination of optic fundi Calculation of BMI from height and weight Auscultation for possible carotid, abdominal, or femoral bruits Palpation of the thyroid gland Examination of the heart and lungs Examination of the abdomen for enlarged kidneys, masses, distended urinary bladder, or abnormal aortic pulsation Palpation of the lower extremities for oedema and pulses Neurological assessment.

White-coat HTN is suspected when the patient has a higher BP reading when taken in the office, compared with a reading taken by themselves at home.

Ambulatory BP monitoring may be helpful in patients with suspected whitecoat HTN, and also in cases of apparent drug resistance or episodic HTN. Ambulatory monitoring may show disparity with office-based BP, but diagnostic guidelines remain the same (2 BP readings on different days greater than stated goals for individual risk factors). Home BP monitoring is useful for the initial diagnosis and the long-term follow-up of HTN. [42] Home BP measurements are as good as ambulatory monitoring and superior to office measurements in regard to their association with pre-clinical organ damage assessed by echocardiographic left ventricular mass index. [43] Physical examination may reveal end-organ damage associated with untreated HTN: for example, retinopathy, vascular bruits, signs of CHF, evidence of aortic aneurysm (pulsatile mass/bruit), LVH (displaced point of maximal impact), or neurological deficit(s). Absence of femoral pulses suggests coarctation of the aorta. An abdominal bruit may suggest aortic aneurysm or renal artery stenosis. Occasionally, patients may have stigmata of endocrinopathy such as Cushing's disease (moon face, centripetal obesity, striae), acromegaly (acral enlargement), Graves' disease (goitre, exophthalmos, pretibial myxoedema), or hypothyroidism (dry skin, delayed return of deep tendon reflexes), indicating a secondary cause of HTN.

Tests
Routine metabolic panel and lipid levels are required. GFR is calculated according to the Modification of Diet in Renal Disease (MDRD) formula. [44] [National Kidney Foundaton: GFR calculator] (external link) In particular, features of the metabolic syndrome (hyperglycaemia, dyslipidaemia) or hyperuricaemia should be noted. Haemoglobin and routine urinalysis with microalbumin are also recommended for possible identification of causes of HTN. An ECG should be obtained. More extensive testing for secondary causes of HTN is generally not indicated, unless BP is difficult to control or clinical or routine lab data suggest identifiable secondary causes such as signs of unprovoked hypokalaemia or renal insufficiency. [1] Echocardiogram and carotid Dopplers may have prognostic implications. They are not routinely recommended but are suggested in patients with other cardiovascular risk factors. There was increased risk of mortality and cardiovascular events in patients with increased left ventricular mass and abnormal geometric left ventricular hypertrophy on echocardiogram. [45] [46] Increased cardiovascular events were associated with higher intima media thickness values on carotid Dopplers. [47]

If secondary HTN is suggested by history, or physical or routine laboratory testing, further testing can be performed. [2]
Signs/symptoms of catecholamine excess require phaeochromocytoma screen. Signs/symptoms of hyper- or hypothyroidism require TSH. Unprovoked hypokalaemia prompts measurement of plasma renin activity (PRA)/aldosterone. Renal artery imaging is done for young patients with difficult-to-control HTN or who have abdominal bruits. [2]
Click to view diagnostic guideline references.

Diagnostic criteria

The seventh report of the Joint National Committee on the Prevention, Detection, Evaluation and Treatment of High Blood Pressure [1]
The categories are based on the average of 2 or more seated BP measurements on 2 separate occasions. -Normal: less than 120/80 mmHg -Pre-HTN: 120 to 139/80 to 89 mmHg -HTN: 140/90 mmHg or greater
Stage 1: 140 to 159/90 to 99 mmHg Stage 2: 160/100 mmHg or greater The main goal of treatment is to decrease the risk of mortality and of cardiovascular and renal morbidity. [4] BP goal should be less than 130/80 mmHg in patients with renal disease, and less than 140/90 mmHg in all other patients. Regarding patients with concomitant diabetes mellitus, there is good-quality evidence that very intensive BP lowering (targeting a systolic pressure <120 mmHg, as compared with targeting <140 mmHg) does not lessen risk (composite outcome: non-fatal MI, non-fatal stroke, or death from cardiovascular cause) and may increase risk of adverse events. [5]

Treatment Options

Treatment Patient group no comorbidity (other than osteoporosis): non-pregnant stage 1 HTN (BP 140 to 159/90 to 99 mmHg) 1st line Treatmenthide all

diuretic monotherapy + lifestyle modification


May be most effective in older and black patients. In several large clinical trials, no other agents have proven superior to thiazide-type diuretics as monotherapy for achieving goal reductions in BP. [92]Indapamide is a non-thiazide (but thiazidelike) diuretic.

Generally well tolerated. The lowest dose should be titrated upwards until a therapeutic effect is achieved or an adverse effect limits further titration.

If low to moderate dose is not effective to reach goal, consider optimising dose or adding a second drug. There is insufficient evidence about which approach is superior. Primary Options hydrochlorothiazide : 12.5 to 50 mg orally once daily Secondary Options chlorothiazide : 125-500 mg/day orally given in 1-2 divided doses OR chlortalidone : 12.5 to 50 mg orally once daily Tertiary Options indapamide : 1.25 to 5 mg orally once daily

2nd

ACE inhibitor/angiotensin-II receptor blocker monotherapy + lifestyle modification


May be effective in younger, especially white patients. If low to moderate dose is not effective to reach goal, dose may be optimised or second drug added. There is insufficient evidence about which approach

Treatment Patient group no comorbidity (other than osteoporosis): non-pregnant line Treatmenthide all

is superior.

Azilsartan is a new angiotensin-II receptor blocker with a unique pharmacological profile, including slowed rates of angiotensin-II type 1 receptor dissociation and improved receptor specificity. It has been shown to have greater efficacy than other angiotensin-II receptor blockers, with similar safety and tolerability. [93] [94] [95] [96] [97]

The lowest dose should be titrated upwards until a therapeutic effect is achieved or an adverse effect limits further titration. Primary Options benazepril : 10-40 mg orally once daily OR captopril : 12.5 to 25 mg orally two to three times daily initially, maximum 150 mg/day OR enalapril : 5-40 mg orally once daily or in 2 divided doses OR fosinopril : 10-40 mg orally once daily or in 2 divided doses, maximum 80 mg/day OR lisinopril : 10-40 mg orally once daily, maximum 80 mg/day OR moexipril : 7.5 to 30 mg orally once daily OR perindopril : 4-8 mg orally once daily OR quinapril : 10-80 mg orally once daily or in 2 divided doses

Treatment Patient group no comorbidity (other than osteoporosis): non-pregnant line Treatmenthide all

OR ramipril : 2.5 to 20 mg orally once daily OR trandolapril : 1-4 mg orally once daily, maximum 8 mg/day Secondary Options candesartan : 8-32 mg orally once daily or in 2 divided doses OR irbesartan : 150-300 mg orally once daily OR losartan : 25-100 mg orally given once daily or in 2 divided doses OR olmesartan : 20-40 mg orally once daily OR telmisartan : 20-80 mg orally once daily OR valsartan : 80-320 mg orally given once daily or in 2 divided doses OR azilsartan : 40-80 mg orally once daily
2nd

beta-blocker monotherapy + lifestyle modification

White patients have shown greater BP lowering when treated with beta-blockers compared with black patients. [98]

If low to moderate dose is not effective to reach goal, dose may be optimised or second drug added. There is insufficient evidence about which approach is superior.

Non-selective beta-blockers include carvedilol (also

Treatment Patient group no comorbidity (other than osteoporosis): non-pregnant line Treatmenthide all

has alpha-blocking properties), labetalol, penbutolol, pindolol, propranolol, and timolol.


Beta-1-selective blockers include acebutolol, atenolol, betaxolol, bisoprolol, and metoprolol. A review of the use of beta-blockers for HTN highlights the demonstrated inferiority of atenolol compared with other antihypertensives, an inferiority not seen with other beta-blocking agents. Atenolol is generally less cardioprotective and has less BP-lowering effects compared with other members of this class. [99] [100]

Abrupt cessation of therapy with certain betablocking agents has led to exacerbations of angina pectoris and, in some cases, MI. All beta-blockers should be weaned over 1 to 2 weeks and patients should be monitored for symptoms of angina.

The lowest dose should be titrated upwards until a therapeutic effect is achieved or an adverse effect limits further titration. Primary Options acebutolol : 200-800 mg orally once daily or in 2 divided doses, maximum 1200 mg/day OR betaxolol : 5-20 mg orally once daily OR bisoprolol : 2.5 to 10 mg orally once daily, maximum 20 mg/day OR carvedilol : 6.25 mg orally (immediate-release) twice daily initially, increase to 12.5 mg twice daily after 1-2 weeks, maximum 50 mg/day given in 2 divided doses

Treatment Patient group no comorbidity (other than osteoporosis): non-pregnant line Treatmenthide all

OR labetalol : 100-400 mg orally twice daily, maximum 2400 mg/day given in 2-3 divided doses OR metoprolol : 50 mg orally (regular-release) twice daily initially, increase at weekly intervals to maximum 100-450 mg/day given in 2-3 divided doses OR nebivolol : 5 mg orally once daily initially, increase at 2-week intervals, maximum 40 mg/day OR propranolol : 40 mg orally (immediate-release) twice daily initially, increasing to maximum 640 mg/day as tolerated Secondary Options atenolol : 25-100 mg orally once daily
2nd

dihydropyridine CCB monotherapy + lifestyle modification


May be effective in older or black patients. Dihydropyridine calcium-channel blockers (CCBs) are peripheral vasodilators. If low-moderate dose is not effective to reach goal, dose may be optimised or second drug added. There is insufficient evidence about which approach is superior.

The lowest dose should be titrated upwards until a therapeutic effect is achieved or an adverse effect limits further titration. Primary Options amlodipine : 2.5 to 10 mg orally once daily OR

Treatment Patient group no comorbidity (other than osteoporosis): non-pregnant line Treatmenthide all

felodipine : 2.5 to 10 mg orally once daily, maximum 20 mg/day OR isradipine : 2.5 to 10 mg/day orally given in 2 divided doses OR nicardipine : 20-40 mg orally (regular-release) three times daily OR nifedipine : 30-60 mg orally (extended-release) once daily OR nisoldipine : 20 mg orally once daily, maximum 60 mg/day
stage 1 not at goal with monotherapy or stage 2 (BP 160/100 mmHg) 1st

thiazide + ACE inhibitor/angiotensin-II receptor blocker + lifestyle modification


Angiotensin-II receptor blockers may be used if ACE inhibitors are not tolerated. The lowest dose should be titrated upwards until a therapeutic effect is achieved or an adverse effect limits further titration. Primary Options hydrochlorothiazide : 12.5 to 50 mg orally once daily -- AND -benazepril : 10-40 mg orally once daily or captopril : 12.5 to 25 mg orally two to three times daily initially, maximum 150 mg/day or enalapril : 5-40 mg orally once daily or in 2 divided

Treatment Patient group no comorbidity (other than osteoporosis): non-pregnant line Treatmenthide all

doses or fosinopril : 10-40 mg orally once daily or in 2 divided doses, maximum 80 mg/day or lisinopril : 10-40 mg orally once daily, maximum 80 mg/day or moexipril : 7.5 to 30 mg orally once daily or perindopril : 4-8 mg orally once daily or quinapril : 10-80 mg orally once daily or in 2 divided doses or ramipril : 2.5 to 20 mg orally once daily or trandolapril : 1-4 mg orally once daily, maximum 8 mg/day Secondary Options hydrochlorothiazide : 12.5 to 50 mg orally once daily -- AND -candesartan : 8-32 mg orally once daily or in 2 divided doses or irbesartan : 150-300 mg orally once daily or losartan : 25-100 mg orally once daily or in 2 divided doses or olmesartan : 20-40 mg orally once daily

Treatment Patient group no comorbidity (other than osteoporosis): non-pregnant line Treatmenthide all

or telmisartan : 20-80 mg orally once daily or valsartan : 80-320 mg orally given once daily or in 2 divided doses
2nd

ACE inhibitor/angiotensin-II receptor blocker + dihydropyridine CCB + lifestyle modification


Angiotensin-II receptor blockers may be used if ACE inhibitors are not tolerated. Dihydropyridine calcium-channel blockers (CCBs) are peripheral vasodilators. The lowest dose should be titrated upwards until a therapeutic effect is achieved or an adverse effect limits further titration. Primary Options benazepril : 10-40 mg orally once daily or captopril : 12.5 to 25 mg orally two to three times daily initially, maximum 150 mg/day or enalapril : 5-40 mg orally given once daily or in 2 divided doses or fosinopril : 10-40 mg orally given once daily or in 2 divided doses, maximum 80 mg/day or lisinopril : 10-40 mg orally once daily, maximum 80 mg/day or moexipril : 7.5 to 30 mg orally once daily or

Treatment Patient group no comorbidity (other than osteoporosis): non-pregnant line Treatmenthide all

perindopril : 4-8 mg orally once daily or quinapril : 10-80 mg orally once daily or in 2 divided doses or ramipril : 2.5 to 20 mg orally once daily or trandolapril : 1-4 mg orally once daily, maximum 8 mg/day -- AND -amlodipine : 2.5 to 10 mg orally once daily or felodipine : 2.5 to 10 mg orally once daily, maximum 20 mg/day or isradipine : 2.5 to 10 mg/day orally given in 2 divided doses or nicardipine : 20-40 mg orally (regular-release) three times daily or nifedipine : 30-60 mg orally (extended-release) once daily or nisoldipine : 20 mg orally once daily, maximum 60 mg/day Secondary Options candesartan : 8-32 mg orally once daily or in 2 divided doses or irbesartan : 150-300 mg orally once daily or

Treatment Patient group no comorbidity (other than osteoporosis): non-pregnant line Treatmenthide all

losartan : 25-100 mg orally once daily or in 2 divided doses or olmesartan : 20-40 mg orally once daily or telmisartan : 20-80 mg orally once daily or valsartan : 80-320 mg orally once daily or in 2 divided doses -- AND -amlodipine : 2.5 to 10 mg orally once daily or felodipine : 2.5 to 10 mg orally once daily, maximum 20 mg/day or isradipine : 2.5 to 10 mg/day orally given in 2 divided doses or nicardipine : 20-40 mg orally (regular-release) three times daily or nifedipine : 30-60 mg orally (extended-release) once daily or nisoldipine : 20 mg orally once daily, maximum 60 mg/day
2nd

ACE inhibitor/angiotensin-II receptor blocker + beta-blocker + lifestyle modification


Angiotensin-II receptor blockers may be used if ACE inhibitors are not tolerated. Following abrupt cessation of therapy with certain beta-blocking agents, exacerbations of angina

Treatment Patient group no comorbidity (other than osteoporosis): non-pregnant line Treatmenthide all

pectoris and, in some cases, MI have occurred. All beta-blockers should be weaned over 1 to 2 weeks and patients should be monitored for symptoms of angina.

Beta-blockers may be less well tolerated in patients with reactive airways disease (COPD, asthma). Carvedilol also has alpha-blocking properties. Atenolol is generally less cardioprotective and has less BP-lowering effects compared with other betablockers. [100] Other beta-blockers include nadolol, penbutolol, pindolol, or timolol.

The lowest dose should be titrated upwards until a therapeutic effect is achieved or an adverse effect limits further titration. Primary Options benazepril : 10-40 mg orally once daily or captopril : 12.5 to 25 mg orally two to three times daily initially, maximum 150 mg/day or enalapril : 5-40 mg orally once daily or in 2 divided doses or fosinopril : 10-40 mg orally once daily or in 2 divided doses, maximum 80 mg/day or lisinopril : 10-40 mg orally once daily, maximum 80 mg/day or moexipril : 7.5 to 30 mg orally once daily or perindopril : 4-8 mg orally once daily

Treatment Patient group no comorbidity (other than osteoporosis): non-pregnant line Treatmenthide all

or quinapril : 10-80 mg orally once daily or in 2 divided doses or ramipril : 2.5 to 20 mg orally once daily or trandolapril : 1-4 mg orally once daily, maximum 8 mg/day -- AND -acebutolol : 200-800 mg orally once daily or in 2 divided doses, maximum 1200 mg/day or betaxolol : 5-20 mg orally once daily or bisoprolol : 2.5 to 10 mg orally once daily, maximum 20 mg/day or carvedilol : 6.25 mg orally (immediate-release) twice daily initially, increase to 12.5 mg twice daily after 1-2 weeks, maximum 50 mg/day given in 2 divided doses or labetalol : 100-400 mg orally twice daily, maximum 2400 mg/day given in 2-3 divided doses or metoprolol : 50 mg orally (regular-release) twice daily initially, increase at weekly intervals to maximum 100-450 mg/day given in 2-3 divided doses or nebivolol : 5 mg orally once daily initially, increase at 2-week intervals, maximum 40 mg/day

Treatment Patient group no comorbidity (other than osteoporosis): non-pregnant line Treatmenthide all

or propranolol : 40 mg orally (immediate-release) twice daily initially, increasing to maximum 640 mg/day as tolerated Secondary Options losartan : 25-100 mg orally once daily or in 2 divided doses or olmesartan : 20-40 mg orally once daily or telmisartan : 20-80 mg orally once daily or valsartan : 80-320 mg orally once daily or in 2 divided doses -- AND -acebutolol : 200-800 mg orally once daily or in 2 divided doses, maximum 1200 mg/day or betaxolol : 5-20 mg orally once daily or bisoprolol : 2.5 to 10 mg orally once daily, maximum 20 mg/day or carvedilol : 6.25 mg orally (immediate-release) twice daily initially, increase to 12.5 mg twice daily after 1-2 weeks, maximum 50 mg/day given in 2 divided doses or labetalol : 100-400 mg orally twice daily, maximum 2400 mg/day given in 2-3 divided doses or metoprolol : 50 mg orally (regular-release) twice

Treatment Patient group no comorbidity (other than osteoporosis): non-pregnant line Treatmenthide all

daily initially, increase at weekly intervals to maximum 100-450 mg/day given in 2-3 divided doses or nebivolol : 5 mg orally once daily initially, increase at 2-week intervals, maximum 40 mg/day or propranolol : 40 mg orally (immediate-release) twice daily initially, increasing to maximum 640 mg/day as tolerated
2nd

thiazide + beta-blocker + lifestyle modification

Following abrupt cessation of therapy with certain beta-blocking agents, exacerbations of angina pectoris and, in some cases, MI have occurred. All beta-blockers should be weaned over 1 to 2 weeks and patients should be monitored for symptoms of angina.

Beta-blockers may be less well tolerated in patients with reactive airways disease (COPD, asthma). Carvedilol also has alpha-blocking properties. Atenolol is generally less cardioprotective and less BP-lowering compared with other beta-blockers. [100]

The lowest dose should be titrated upwards until a therapeutic effect is achieved or an adverse effect limits further titration.

Other beta-blockers include nadolol, penbutolol, pindolol, or timolol. Primary Options hydrochlorothiazide : 12.5 to 50 mg orally once daily

Treatment Patient group no comorbidity (other than osteoporosis): non-pregnant line Treatmenthide all

-- AND -acebutolol : 200-800 mg orally once daily or in 2 divided doses, maximum 1200 mg/day or betaxolol : 5-20 mg orally once daily or bisoprolol : 2.5 to 10 mg orally once daily, maximum 20 mg/day or carvedilol : 6.25 mg orally (immediate-release) twice daily initially, increase to 12.5 mg twice daily after 1-2 weeks, maximum 50 mg/day given in 2 divided doses or labetalol : 100-400 mg orally twice daily, maximum 2400 mg/day given in 2-3 divided doses or metoprolol : 50 mg orally (regular-release) twice daily initially, increase at weekly intervals to maximum 100-450 mg/day given in 2-3 divided doses or nebivolol : 5 mg orally once daily initially, increase at 2-week intervals, maximum 40 mg/day or propranolol : 40 mg orally (immediate-release) twice daily initially, increasing to maximum 640 mg/day as tolerated
3rd

beta-blocker + dihydropyridine CCB + lifestyle modification

Following abrupt cessation of therapy with certain beta-blocking agents, exacerbations of angina

Treatment Patient group no comorbidity (other than osteoporosis): non-pregnant line Treatmenthide all

pectoris and, in some cases, MI have occurred. All beta-blockers should be weaned over 1 to 2 weeks and patients should be monitored for symptoms of angina.

Carvedilol also has alpha-blocking properties. Other beta-blockers include nadolol, penbutolol, pindolol, or timolol.

Beta-blockers may be less well tolerated in patients with reactive airways disease (COPD, asthma). Dihydropyridine calcium-channel blockers (CCBs) are peripheral vasodilators. Their adverse-effect profile is driven by the peripheral vasodilation and includes peripheral oedema, flushing, and gingival hyperplasia.

Avoid combination of non-dihydropyridine CCBs (verapamil or diltiazem) plus beta-blocker, because of potential bradycardia or AV block.

The lowest dose should be titrated upwards until a therapeutic effect is achieved or an adverse effect limits further titration. Primary Options acebutolol : 200-800 mg orally once daily or in 2 divided doses, maximum 1200 mg/day or betaxolol : 5-20 mg orally once daily or bisoprolol : 2.5 to 10 mg orally once daily, maximum 20 mg/day or carvedilol : 6.25 mg orally (immediate-release) twice daily initially, increase to 12.5 mg twice daily

Treatment Patient group no comorbidity (other than osteoporosis): non-pregnant line Treatmenthide all

after 1-2 weeks, maximum 50 mg/day given in 2 divided doses or labetalol : 100-400 mg orally twice daily, maximum 2400 mg/day given in 2-3 divided doses or metoprolol : 50 mg orally (regular-release) twice daily initially, increase at weekly intervals to maximum 100-450 mg/day given in 2-3 divided doses or nebivolol : 5 mg orally once daily initially, increase at 2-week intervals, maximum 40 mg/day or propranolol : 40 mg orally (immediate-release) twice daily initially, increasing to maximum 640 mg/day as tolerated -- AND -amlodipine : 2.5 to 10 mg orally once daily or felodipine : 2.5 to 10 mg orally once daily, maximum 20 mg/day or isradipine : 2.5 to 10 mg/day orally given in 2 divided doses or nicardipine : 20-40 mg orally (regular-release) three times daily or nifedipine : 30-60 mg orally (extended-release) once daily or

Treatment Patient group no comorbidity (other than osteoporosis): non-pregnant line Treatmenthide all

nisoldipine : 20 mg orally once daily, maximum 60 mg/day

concomitant CAD without CHF: non-pregnant stage 1 HTN (BP 140 to 159/90 to 99 mmHg) 1st

beta-blocker monotherapy + lifestyle modification


Cardioprotective effects in patients with CAD. Vary in lipid solubility, selectiveness for beta-2 receptors, intrinsic sympathomimetic activity, and alpha-blocker activity. Beta-blockers decrease myocardial wall stress and lessen myocardial oxygen demand.

Following abrupt cessation of therapy with certain beta-blocking agents, exacerbations of angina pectoris and, in some cases, MI have occurred. All beta-blockers should be weaned over 1 to 2 weeks and patients should be monitored for symptoms of angina.

Beta-blockers may be less well tolerated in patients with reactive airways disease (COPD, asthma). Many patients with CAD also take nitrates, which act as exogenous nitric oxide (NO) donor. Modest reductions in systolic BP can be observed, but the FDA has not approved the use of nitrates solely as antihypertensive therapy. [15]

Non-selective beta-blockers include carvedilol (also has alpha-blocking properties), labetalol, penbutolol, pindolol, propranolol, and timolol.

Beta-1-selective blockers include acebutolol, atenolol, betaxolol, bisoprolol, and metoprolol. Atenolol is generally less cardioprotective and has less BP-lowering effects compared with other

Treatment Patient group no comorbidity (other than osteoporosis): non-pregnant line Treatmenthide all

members of this class. [100]

The lowest dose should be titrated upwards until a therapeutic effect is achieved or an adverse effect limits further titration. Primary Options acebutolol : 200-800 mg orally once daily or in 2 divided doses, maximum 1200 mg/day OR betaxolol : 5-20 mg orally once daily OR bisoprolol : 2.5 to 10 mg orally once daily, maximum 20 mg/day OR carvedilol : 6.25 mg orally (immediate-release) twice daily initially, increase to 12.5 mg twice daily after 1-2 weeks, maximum 50 mg/day given in 2 divided doses OR labetalol : 100-400 mg orally twice daily, maximum 2400 mg/day given in 2-3 divided doses OR metoprolol : 50 mg orally (regular-release) twice daily initially, increase at weekly intervals to maximum 100-450 mg/day given in 2-3 divided doses OR nebivolol : 5 mg orally once daily initially, increase at 2-week intervals, maximum 40 mg/day OR propranolol : 40 mg orally (immediate-release) twice daily initially, increasing to maximum 640 mg/day as tolerated

Treatment Patient group no comorbidity (other than osteoporosis): non-pregnant line Treatmenthide all

Secondary Options atenolol : 25-100 mg orally once daily


2nd

dihydropyridine CCB monotherapy + lifestyle modification

Dihydropyridine calcium-channel blockers (CCBs) are peripheral vasodilators. The lowest dose should be titrated upwards until a therapeutic effect is achieved or an adverse effect limits further titration. Primary Options amlodipine : 2.5 to 10 mg orally once daily OR felodipine : 2.5 to 10 mg orally once daily, maximum 20 mg/day OR isradipine : 2.5 to 10 mg/day orally given in 2 divided doses OR nicardipine : 20-40 mg orally (regular-release) three times daily OR nifedipine : 30-60 mg orally (extended-release) once daily OR nisoldipine : 20 mg orally once daily, maximum 60 mg/day

stage 1 not at goal with monotherapy or stage 2 (BP 160/100 mmHg)

1st

beta-blocker + dihydropyridine CCB + lifestyle modification

Following abrupt cessation of therapy with certain beta-blocking agents, exacerbations of angina pectoris and, in some cases, MI have occurred. All beta-blockers should be weaned over 1 to 2 weeks and patients should be monitored for symptoms of

Treatment Patient group no comorbidity (other than osteoporosis): non-pregnant line Treatmenthide all

angina.

Beta-blockers may be less well tolerated in patients with reactive airways disease (COPD, asthma). Carvedilol also has alpha-blocking properties. Other beta-blockers include nadolol, penbutolol, pindolol, or timolol.

Dihydropyridine calcium-channel blockers (CCBs) are peripheral vasodilators. Avoid combination of non-dihydropyridine CCB (verapamil or diltiazem) and beta-blocker, because of potential bradycardia or AV block.

The lowest dose should be titrated upwards until a therapeutic effect is achieved or an adverse effect limits further titration. Primary Options acebutolol : 200-800 mg orally once daily or in 2 divided doses, maximum 1200 mg/day or betaxolol : 5-20 mg orally once daily or bisoprolol : 2.5 to 10 mg orally once daily, maximum 20 mg/day or carvedilol : 6.25 mg orally (immediate-release) twice daily initially, increase to 12.5 mg twice daily after 1-2 weeks, maximum 50 mg/day given in 2 divided doses or labetalol : 100-400 mg orally twice daily, maximum 2400 mg/day given in 2-3 divided doses or metoprolol : 50 mg orally (regular-release) twice

Treatment Patient group no comorbidity (other than osteoporosis): non-pregnant line Treatmenthide all

daily initially, increase at weekly intervals to maximum 100-450 mg/day given in 2-3 divided doses or nebivolol : 5 mg orally once daily initially, increase at 2-week intervals, maximum 40 mg/day or propranolol : 40 mg orally (immediate-release) twice daily initially, increasing to maximum 640 mg/day as tolerated -- AND -amlodipine : 2.5 to 10 mg orally once daily or felodipine : 2.5 to 10 mg orally once daily, maximum 20 mg/day or isradipine : 2.5 to 10 mg/day orally given in 2 divided doses or nicardipine : 20-40 mg orally (regular-release) three times daily or nifedipine : 30-60 mg orally (extended-release) once daily or nisoldipine : 20 mg orally once daily, maximum 60 mg/day
2nd

beta-blocker + ACE inhibitor/angiotensin-II receptor blocker + lifestyle modification


Stage 2 is defined as BP 160/100 mmHg or greater. Angiotensin-II receptor blockers may be used if ACE inhibitors are not tolerated.

Treatment Patient group no comorbidity (other than osteoporosis): non-pregnant line Treatmenthide all

Following abrupt cessation of therapy with certain beta-blocking agents, exacerbations of angina pectoris and, in some cases, MI have occurred. All beta-blockers should be weaned over 1 to 2 weeks and patients should be monitored for symptoms of angina.

Beta-blockers may be less well tolerated in patients with reactive airways disease (COPD, asthma). Carvedilol also has alpha-blocking properties. Other beta-blockers include nadolol, penbutolol, pindolol, or timolol. Primary Options benazepril : 10-40 mg orally once daily or captopril : 12.5 to 25 mg orally two to three times daily initially, maximum 150 mg/day or enalapril : 5-40 mg orally once daily or in 2 divided doses or fosinopril : 10-40 mg orally once daily or in 2 divided doses, maximum 80 mg/day or lisinopril : 10-40 mg orally once daily, maximum 80 mg/day or moexipril : 7.5 to 30 mg orally once daily or perindopril : 4-8 mg orally once daily or quinapril : 10-80 mg orally once daily or in 2 divided doses

Treatment Patient group no comorbidity (other than osteoporosis): non-pregnant line Treatmenthide all

or ramipril : 2.5 to 20 mg orally once daily or trandolapril : 1-4 mg orally once daily, maximum 8 mg/day -- AND -acebutolol : 200-800 mg orally once daily or in 2 divided doses, maximum 1200 mg/day or betaxolol : 5-20 mg orally once daily or bisoprolol : 2.5 to 10 mg orally once daily, maximum 20 mg/day or carvedilol : 6.25 mg orally (immediate-release) twice daily initially, increase to 12.5 mg twice daily after 1-2 weeks, maximum 50 mg/day given in 2 divided doses or labetalol : 100-400 mg orally twice daily, maximum 2400 mg/day given in 2-3 divided doses or metoprolol : 50 mg orally (regular-release) twice daily initially, increase at weekly intervals to maximum 100-450 mg/day given in 2-3 divided doses or nebivolol : 5 mg orally once daily initially, increase at 2-week intervals, maximum 40 mg/day or propranolol : 40 mg orally (immediate-release) twice daily initially, increasing to maximum 640 mg/day as tolerated

Treatment Patient group no comorbidity (other than osteoporosis): non-pregnant line Treatmenthide all

Secondary Options losartan : 25-100 mg orally once daily or in 2 divided doses or olmesartan : 20-40 mg orally once daily or telmisartan : 20-80 mg orally once daily or valsartan : 80-320 mg orally once daily or in 2 divided doses -- AND -acebutolol : 200-800 mg orally given once daily or in 2 divided doses, maximum 1200 mg/day or betaxolol : 5-20 mg orally once daily or bisoprolol : 2.5 to 10 mg orally once daily, maximum 20 mg/day or carvedilol : 6.25 mg orally (immediate-release) twice daily initially, increase to 12.5 mg twice daily after 1-2 weeks, maximum 50 mg/day given in 2 divided doses or labetalol : 100-400 mg orally twice daily, maximum 2400 mg/day given in 2-3 divided doses or metoprolol : 50 mg orally (regular-release) twice daily initially, increase at weekly intervals to maximum 100-450 mg/day given in 2-3 divided doses or

Treatment Patient group no comorbidity (other than osteoporosis): non-pregnant line Treatmenthide all

nebivolol : 5 mg orally once daily initially, increase at 2-week intervals, maximum 40 mg/day or propranolol : 40 mg orally (immediate-release) twice daily initially, increasing to maximum 640 mg/day as tolerated
3rd

thiazide + beta-blocker + lifestyle modification

Following abrupt cessation of therapy with certain beta-blocking agents, exacerbations of angina pectoris and, in some cases, MI have occurred. All beta-blockers should be weaned over 1 to 2 weeks and patients should be monitored for symptoms of angina.

Beta-blockers may be less well tolerated in patients with reactive airways disease (COPD, asthma). Carvedilol also has alpha-blocking properties. Other beta-blockers include nadolol, penbutolol, pindolol, or timolol.

The lowest dose should be titrated upwards until a therapeutic effect is achieved or an adverse effect limits further titration. Primary Options hydrochlorothiazide : 12.5 to 50 mg orally once daily -- AND -acebutolol : 200-800 mg orally given once daily or in 2 divided doses, maximum 1200 mg/day or betaxolol : 5-20 mg orally once daily or bisoprolol : 2.5 to 10 mg orally once daily, maximum

Treatment Patient group no comorbidity (other than osteoporosis): non-pregnant line Treatmenthide all

20 mg/day or carvedilol : 6.25 mg orally (immediate-release) twice daily initially, increase to 12.5 mg twice daily after 1-2 weeks, maximum 50 mg/day given in 2 divided doses or labetalol : 100-400 mg orally twice daily, maximum 2400 mg/day given in 2-3 divided doses or metoprolol : 50 mg orally (regular-release) twice daily initially, increase at weekly intervals to maximum 100-450 mg/day given in 2-3 divided doses or nebivolol : 5 mg orally once daily initially, increase at 2-week intervals, maximum 40 mg/day or propranolol : 40 mg orally (immediate-release) twice daily initially, increasing to maximum 640 mg/day as tolerated
3rd

ACE inhibitor/angiotensin-II receptor blocker + thiazide + lifestyle modification


Angiotensin-II receptor blockers may be used if ACE inhibitors are not tolerated. The lowest dose should be titrated upwards until a therapeutic effect is achieved or an adverse effect limits further titration. Primary Options hydrochlorothiazide : 12.5 to 50 mg orally once daily

Treatment Patient group no comorbidity (other than osteoporosis): non-pregnant line Treatmenthide all

-- AND -benazepril : 10-40 mg orally once daily or captopril : 12.5 to 25 mg orally two to three times daily initially, maximum 150 mg/day or enalapril : 5-40 mg orally once daily or in 2 divided doses or fosinopril : 10-40 mg orally once daily or in 2 divided doses, maximum 80 mg/day or lisinopril : 10-40 mg orally once daily, maximum 80 mg/day or moexipril : 7.5 to 30 mg orally once daily or perindopril : 4-8 mg orally once daily or quinapril : 10-80 mg orally once daily or in 2 divided doses or ramipril : 2.5 to 20 mg orally once daily or trandolapril : 1-4 mg orally once daily, maximum 8 mg/day Secondary Options hydrochlorothiazide : 12.5 to 50 mg orally once daily -- AND -candesartan : 8-32 mg orally once daily or in 2

Treatment Patient group no comorbidity (other than osteoporosis): non-pregnant line Treatmenthide all

divided doses or irbesartan : 150-300 mg orally once daily or losartan : 25-100 mg orally once daily or in 2 divided doses or olmesartan : 20-40 mg orally once daily or telmisartan : 20-80 mg orally once daily or valsartan : 80-320 mg orally once daily or in 2 divided doses

concomitant CHF with ejection fraction less than 55%: nonpregnant NYHA class I or II 1st

ACE inhibitor/angiotensin-II receptor blocker + beta-blocker + lifestyle modification


Agents are slowly titrated up to doses used in studies. Angiotensin-II receptor blockers may be used if ACE inhibitors are not tolerated. Following abrupt cessation of therapy with certain beta-blocking agents, exacerbations of angina pectoris and, in some cases, MI have occurred. All beta-blockers should be weaned over 1 to 2 weeks and patients should be monitored for symptoms of angina. Metoprolol and bisoprolol are beta-1 selective; carvedilol is beta-1 and beta-2 selective and also has alpha-blocking properties. Loop diuretics may be used for fluid overload.

Treatment Patient group no comorbidity (other than osteoporosis): non-pregnant line Treatmenthide all

The lowest dose should be titrated upwards until a therapeutic effect is achieved or an adverse effect limits further titration. Primary Options lisinopril : 2.5 to 5 mg orally once daily initially, gradually increase by 10 mg increments every 2 weeks, maximum 40 mg/day or enalapril : 2.5 mg orally once or twice daily initially, gradually increase at 1-2 weekly intervals, maximum 10-20 mg twice daily or captopril : 12.5 to 25 mg orally two to three times daily initially, maximum 150 mg/day or ramipril : 1.25 to 2.5 mg orally once daily initially, gradually increase to 10 mg once daily -- AND -carvedilol : 3.125 mg orally (immediate-release) twice daily initially, titrate to 6.25 mg, 12.5 mg, and then 25 mg twice daily at 2 week intervals, maximum 50 mg twice daily if body-weight >85 kg or metoprolol : 25 mg orally (extended-release) once daily initially, double the dose at 2 week intervals, maximum 200 mg once daily or bisoprolol : 1.25 mg orally once daily initially, gradually increase to 10 mg once daily Secondary Options candesartan : 4 mg orally once daily initially, double the dose at 2 week intervals, maximum 32 mg once

Treatment Patient group no comorbidity (other than osteoporosis): non-pregnant line Treatmenthide all

daily or valsartan : 40 mg orally twice daily initially, gradually increase to 160 mg twice daily -- AND -carvedilol : 3.125 mg orally (immediate-release) twice daily initially, titrate to 6.25 mg, 12.5 mg, and then 25 mg twice daily at 2 week intervals, maximum 50 mg twice daily if body-weight >85 kg or metoprolol : 25 mg orally (extended-release) once daily initially, double the dose at 2 week intervals, maximum 200 mg once daily or bisoprolol : 1.25 mg orally once daily initially, gradually increase to 10 mg once daily adjunct [?] non-aldosterone-blocking diuretics

Diuretics may be used for fluid overload. The lowest dose should be titrated upwards until a therapeutic effect is achieved or an adverse effect limits further titration. Primary Options furosemide : 20-120 mg orally once daily or in 2 divided doses OR bumetanide : 0.5 to 2 mg orally once daily, maximum 10 mg/day Secondary Options metolazone : 0.5 to 1 mg orally once daily

NYHA class III or IV

1st

ACE inhibitor/angiotensin-II receptor blocker + beta-blocker

Treatment Patient group no comorbidity (other than osteoporosis): non-pregnant line Treatmenthide all

+ aldosterone antagonist + lifestyle modification


Agents are slowly titrated up to doses used in studies. Angiotensin-II receptor blockers may be used if ACE inhibitors are not tolerated. Following abrupt cessation of therapy with certain beta-blocking agents, exacerbations of angina pectoris and, in some cases, MI have occurred. All beta-blockers should be weaned over 1 to 2 weeks and patients should be monitored for symptoms of angina. Metoprolol and bisoprolol are beta-1 selective; carvedilol is beta-1 and beta-2 selective and also has alpha-blocking properties. Aldosterone antagonists should be used in NYHA class III or IV.

Loop diuretics may be used for fluid overload. The lowest dose should be titrated upwards until a therapeutic effect is achieved or an adverse effect limits further titration. Primary Options lisinopril : 2.5 to 5 mg orally once daily initially, gradually increase by 10 mg increments every 2 weeks, maximum 40 mg/day or enalapril : 2.5 mg orally once or twice daily initially, gradually increase at 1-2 weekly intervals, maximum 10-20 mg twice daily or captopril : 12.5 to 25 mg orally two to three times daily initially, maximum 150 mg/day or ramipril : 1.25 to 2.5 mg orally once daily initially, gradually increase to 10 mg once daily

Treatment Patient group no comorbidity (other than osteoporosis): non-pregnant line Treatmenthide all

-- AND -carvedilol : 3.125 mg orally (immediate-release) twice daily initially, titrate to 6.25 mg, 12.5 mg, and then 25 mg twice daily or metoprolol : 12.5 mg orally (extended-release) once daily initially, double the dose at 2 week intervals, maximum 200 mg once daily or bisoprolol : 1.25 mg orally once daily initially, gradually increase to 10 mg once daily -- AND -spironolactone : 12.5 to 25 mg orally once daily, maximum 50 mg/day or eplerenone : 25-50 mg orally once daily Secondary Options candesartan : 4 mg orally once daily initially, double the dose at 2 week intervals, maximum 32 mg once daily or valsartan : 40 mg orally twice daily initially, gradually increase to 160 mg twice daily -- AND -carvedilol : 3.125 mg orally (immediate-release) twice daily initially, titrate to 6.25 mg, 12.5 mg, and then 25 mg twice daily or metoprolol : 12.5 mg orally (extended-release) once daily initially, double the dose at 2 week intervals, maximum 200 mg once daily or

Treatment Patient group no comorbidity (other than osteoporosis): non-pregnant line Treatmenthide all

bisoprolol : 1.25 mg orally once daily initially, gradually increase to 10 mg once daily -- AND -spironolactone : 12.5 to 25 mg orally once daily, maximum 50 mg/day or eplerenone : 25-50 mg orally once daily adjunct [?] non-aldosterone-blocking diuretics

Diuretics may be used for fluid overload. The lowest dose should be titrated upwards until a therapeutic effect is achieved or an adverse effect limits further titration. Primary Options furosemide : 20-120 mg orally once daily or in 2 divided doses OR bumetanide : 0.5 to 2 mg orally once daily, maximum 10 mg/day Secondary Options metolazone : 0.5 to 1 mg orally once daily

adjunct [?]

substitution or addition of isosorbide dinitrate/hydralazine

Hydralazine/isosorbide dinitrate may be useful for those intolerant to or refractory to other agents. May offer additional mortality benefit in black patients when added to optimised ACE inhibition plus betablockade plus aldosterone antagonism. [68] Primary Options hydralazine/isosorbide dinitrate : 20 mg (isosorbide

Treatment Patient group no comorbidity (other than osteoporosis): non-pregnant line Treatmenthide all

dinitrate)/37.5 mg (hydralazine) orally three times daily, maximum 40 mg (isosorbide dinitrate)/75 mg (hydralazine) three times daily

concomitant LVH without CAD: non-pregnant

1st

angiotensin-II receptor blocker/ACE inhibitor monotherapy + lifestyle modification


Angiotensin-II receptor blockers have been shown to promote regression of LVH. [99] Azilsartan is a new angiotensin-II receptor blocker with a unique pharmacological profile, including slowed rates of angiotensin-II type 1 receptor dissociation and improved receptor specificity. It has been shown to have greater efficacy than other angiotensin-II receptor blockers, with similar safety and tolerability. [93] [94] [95] [96] [97]

ACE inhibitor may be used as an alternative to angiotensin-II receptor blockers. The lowest dose should be titrated upwards until a therapeutic effect is achieved or an adverse effect limits further titration. Primary Options losartan : 25-100 mg orally once daily or in 2 divided doses OR olmesartan : 20-40 mg orally once daily OR telmisartan : 20-80 mg orally once daily OR valsartan : 80-320 mg orally once daily or in 2 divided doses

Treatment Patient group no comorbidity (other than osteoporosis): non-pregnant line Treatmenthide all

OR azilsartan : 40-80 mg orally once daily Secondary Options benazepril : 10-40 mg orally once daily OR captopril : 12.5 to 25 mg orally two to three times daily initially, maximum 150 mg/day OR enalapril : 5-40 mg orally once daily or in 2 divided doses OR fosinopril : 10-40 mg orally once daily or in 2 divided doses, maximum 80 mg/day OR lisinopril : 10-40 mg orally once daily, maximum 80 mg/day OR moexipril : 7.5 to 30 mg orally once daily OR perindopril : 4-8 mg orally once daily OR quinapril : 10-80 mg orally once daily or in 2 divided doses OR ramipril : 2.5 to 20 mg orally once daily OR trandolapril : 1-4 mg orally once daily, maximum 8 mg/day

concomitant diabetes or chronic

Treatment Patient group no comorbidity (other than osteoporosis): non-pregnant renal disease without cardiovascular disease: nonpregnant stage 1 HTN (BP 140 to 159/90 to 99 mmHg) 1st line Treatmenthide all

ACE inhibitor/angiotensin-II receptor blocker monotherapy + lifestyle modification


Goal BP is less than 130/80 mmHg. The lowest dose should be titrated upwards until a therapeutic effect is achieved or an adverse effect limits further titration. Primary Options benazepril : 10-40 mg orally once daily OR captopril : 12.5 to 25 mg orally two to three times daily initially, maximum 150 mg/day OR enalapril : 5-40 mg orally given once daily or in 2 divided doses OR fosinopril : 10-40 mg orally given once daily or in 2 divided doses, maximum 80 mg/day OR lisinopril : 10-40 mg orally once daily, maximum 80 mg/day OR moexipril : 7.5 to 30 mg orally once daily OR perindopril : 4-8 mg orally once daily OR quinapril : 10-80 mg orally once daily or in 2 divided doses OR ramipril : 2.5 to 20 mg orally once daily

Treatment Patient group no comorbidity (other than osteoporosis): non-pregnant line Treatmenthide all

OR trandolapril : 1-4 mg orally once daily, maximum 8 mg/day Secondary Options losartan : 25-100 mg orally once daily or in 2 divided doses OR olmesartan : 20-40 mg orally once daily OR telmisartan : 20-80 mg orally once daily OR valsartan : 80-320 mg orally once daily or in 2 divided doses
2nd

dihydropyridine CCB monotherapy + lifestyle modification

The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) study showed that chlortalidone, amlodipine, or lisinopril were co-equal for mild HTN in type 2 diabetes. [92]

Dihydropyridine calcium-channel blockers (CCBs) are peripheral vasodilators. The lowest dose should be titrated upwards until a therapeutic effect is achieved or an adverse effect limits further titration. Primary Options amlodipine : 2.5 to 10 mg orally once daily OR felodipine : 2.5 to 10 mg orally once daily, maximum 20 mg/day OR isradipine : 2.5 to 10 mg/day orally given in 2

Treatment Patient group no comorbidity (other than osteoporosis): non-pregnant line Treatmenthide all

divided doses OR nicardipine : 20-40 mg orally (regular-release) three times daily OR nifedipine : 30-60 mg orally (extended-release) once daily OR nisoldipine : 20 mg orally once daily, maximum 60 mg/day
2nd

thiazide monotherapy + lifestyle modification


Goal BP less than 130/80 mmHg. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) study showed that chlortalidone, amlodipine, or lisinopril were co-equal for mild HTN in patients with at least one cardiovascular risk factor.[92]

Given their once daily dosing, minor adverse-effect profile, and relatively low cost, thiazide diuretics are recommended in people with diabetes without microalbuminuria.

In diabetes plus microalbuminuria, recommend ACE inhibitors or angiotensin-II receptor blockers . May be less efficacious for LVH remodelling compared with ACE inhibitor/angiotensin-II receptor blocker or calcium-channel blockers.

Thiazides may not be as effective if GFR is less than 20 mL/minute/1.73m^2. The lowest dose should be titrated upwards until a therapeutic effect is achieved or an adverse effect limits further titration.

Treatment Patient group no comorbidity (other than osteoporosis): non-pregnant line Treatmenthide all

Primary Options hydrochlorothiazide : 12.5 to 50 mg orally once daily Secondary Options chlorothiazide : 125-500 mg/day orally given in 1-2 divided doses OR chlortalidone : 12.5 to 50 mg orally once daily
3rd

beta-blocker monotherapy + lifestyle modification

Following abrupt cessation of therapy with certain beta-blocking agents, exacerbations of angina pectoris and, in some cases, MI have occurred. All beta-blockers should be weaned over 1 to 2 weeks and patients should be monitored for symptoms of angina.

Beta-blockers may be less well tolerated in patients with reactive airways disease (COPD, asthma). Carvedilol also has alpha-blocking properties. Atenolol is generally less cardioprotective and has less BP-lowering effects compared with other betablockers. [100] Other beta-blockers include nadolol, penbutolol, pindolol, or timolol.

The lowest dose should be titrated upwards until a therapeutic effect is achieved or an adverse effect limits further titration. Primary Options acebutolol : 200-800 mg orally once daily or in 2 divided doses, maximum 1200 mg/day OR betaxolol : 5-20 mg orally once daily

Treatment Patient group no comorbidity (other than osteoporosis): non-pregnant line Treatmenthide all

OR bisoprolol : 2.5 to 10 mg orally once daily, maximum 20 mg/day OR carvedilol : 6.25 mg orally (immediate-release) twice daily initially, increase to 12.5 mg twice daily after 1-2 weeks, maximum 50 mg/day given in 2 divided doses OR labetalol : 100-400 mg orally twice daily, maximum 2400 mg/day given in 2-3 divided doses OR metoprolol : 50 mg orally (regular-release) twice daily initially, increase at weekly intervals to maximum 100-450 mg/day given in 2-3 divided doses OR nebivolol : 5 mg orally once daily initially, increase at 2-week intervals, maximum 40 mg/day OR propranolol : 40 mg orally (immediate-release) twice daily initially, increasing to maximum 640 mg/day as tolerated Secondary Options atenolol : 25-100 mg orally once daily
stage 1 not at goal with monotherapy or stage 2 (BP 160/100 mmHg) 1st

ACE inhibitor/angiotensin-II receptor blocker + thiazide + lifestyle modification


Goal BP is less than 130/80 mmHg. ACE inhibitors are first-line therapy for comorbid diabetes and renal disease with angiotensin-II receptor blockers as an alternative. Angiotensin-II receptor blockers are first-line therapy for comorbid

Treatment Patient group no comorbidity (other than osteoporosis): non-pregnant line Treatmenthide all

LVH, with ACE inhibitors as an alternative.

The lowest dose should be titrated upwards until a therapeutic effect is achieved or an adverse effect limits further titration. Primary Options hydrochlorothiazide : 12.5 to 50 mg orally once daily -- AND -benazepril : 10-40 mg orally once daily or captopril : 12.5 to 25 mg orally two to three times daily initially, maximum 150 mg/day or enalapril : 10-40 mg orally once daily or in 2 divided doses, maximum 80 mg/day or fosinopril : 10-40 mg orally once daily, maximum 80 mg/day or lisinopril : 7.5 to 30 mg orally once daily or moexipril : 4-8 mg orally once daily or perindopril : 10-80 mg orally once daily or in 2 divided doses or quinapril : 12.5 to 25 mg orally given 2-3 times daily initially, maximum 50 mg three times daily or ramipril : 2.5 to 20 mg orally once daily or trandolapril : 1-4 mg orally once daily, maximum 8

Treatment Patient group no comorbidity (other than osteoporosis): non-pregnant line Treatmenthide all

mg/day Secondary Options hydrochlorothiazide : 12.5 to 50 mg orally once daily -- AND -candesartan : 8-32 mg orally given once daily or in 2 divided doses or irbesartan : 150-300 mg orally once daily or losartan : 25-100 mg orally given once daily or in 2 divided doses or olmesartan : 20-40 mg orally once daily or telmisartan : 20-80 mg orally once daily or valsartan : 80-320 mg orally given once daily or in 2 divided doses
2nd

ACE inhibitor/angiotensin-II receptor blocker + dihydropyridine CCB + lifestyle modification


Goal BP less than 130/80 mmHg. ACE inhibitors are first-line therapy for comorbid diabetes and renal disease with angiotensin-II receptor blockers as an alternative. Angiotensin-II receptor blockers are first-line therapy for comorbid LVH, with ACE inhibitors as an alternative.

Dihydropyridine calcium-channel blockers (CCBs) are peripheral vasodilators. The lowest dose should be titrated upwards until a therapeutic effect is achieved or an adverse effect

Treatment Patient group no comorbidity (other than osteoporosis): non-pregnant line Treatmenthide all

limits further titration. Primary Options benazepril : 10-40 mg orally once daily or captopril : 12.5 to 25 mg orally two to three times daily initially, maximum 150 mg/day or enalapril : 5-40 mg orally given once daily or in 2 divided doses or fosinopril : 10-40 mg orally given once daily or in 2 divided doses, maximum 80 mg/day or lisinopril : 10-40 mg orally once daily, maximum 80 mg/day or moexipril : 7.5 to 30 mg orally once daily or perindopril : 4-8 mg orally once daily or quinapril : 10-80 mg orally once daily or in 2 divided doses or ramipril : 2.5 to 20 mg orally once daily or trandolapril : 1-4 mg orally once daily, maximum 8 mg/day -- AND -amlodipine : 2.5 to 10 mg orally once daily or felodipine : 2.5 to 10 mg orally once daily, maximum 20 mg/day

Treatment Patient group no comorbidity (other than osteoporosis): non-pregnant line Treatmenthide all

or isradipine : 2.5 to 10 mg/day orally given in 2 divided doses or nicardipine : 20-40 mg orally (regular-release) three times daily or nifedipine : 30-60 mg orally (extended-release) once daily or nisoldipine : 20 mg orally once daily, maximum 60 mg/day Secondary Options candesartan : 8-32 mg orally once daily or in 2 divided doses or irbesartan : 150-300 mg orally once daily or losartan : 25-100 mg orally once daily or in 2 divided doses or olmesartan : 20-40 mg orally once daily or telmisartan : 20-80 mg orally once daily or valsartan : 80-320 mg orally given once daily or in 2 divided doses -- AND -amlodipine : 2.5 to 10 mg orally once daily or felodipine : 2.5 to 10 mg orally once daily, maximum 20 mg/day

Treatment Patient group no comorbidity (other than osteoporosis): non-pregnant line Treatmenthide all

or isradipine : 2.5 to 10 mg/day orally given in 2 divided doses or nicardipine : 20-40 mg orally (regular-release) three times daily or nifedipine : 30-60 mg orally (extended-release) once daily or nisoldipine : 20 mg orally once daily, maximum 60 mg/day
3rd

ACE inhibitor/angiotensin-II receptor blocker + beta-blocker + lifestyle modification


Goal BP is less than 130/80 mmHg. ACE inhibitors are first-line therapy for comorbid diabetes and renal disease with angiotensin-II receptor blockers as an alternative. Angiotensin-II receptor blockers are first-line therapy for comorbid LVH, with ACE inhibitors as an alternative.

Following abrupt cessation of therapy with certain beta-blocking agents, exacerbations of angina pectoris and, in some cases, MI have occurred. All beta-blockers should be weaned over 1 to 2 weeks and patients should be monitored for symptoms of angina.

Beta-blockers may be poorly tolerated in patients with asthma or COPD. Carvedilol also has alpha-blocking properties. Other beta-blockers include nadolol, penbutolol, pindolol, or timolol.

Treatment Patient group no comorbidity (other than osteoporosis): non-pregnant line Treatmenthide all

The lowest dose should be titrated upwards until a therapeutic effect is achieved or an adverse effect limits further titration. Primary Options benazepril : 10-40 mg orally once daily or captopril : 12.5 to 25 mg orally two to three times daily initially, maximum 150 mg/day or enalapril : 5-40 mg orally once daily or in 2 divided doses or fosinopril : 10-40 mg orally given once daily or in 2 divided doses, maximum 80 mg/day or lisinopril : 10-40 mg orally once daily, maximum 80 mg/day or moexipril : 7.5 to 30 mg orally once daily or perindopril : 4-8 mg orally once daily or quinapril : 10-80 mg orally once daily or in 2 divided doses or ramipril : 2.5 to 20 mg orally once daily or trandolapril : 1-4 mg orally once daily, maximum 8 mg/day -- AND -acebutolol : 200-800 mg orally once daily or in 2

Treatment Patient group no comorbidity (other than osteoporosis): non-pregnant line Treatmenthide all

divided doses, maximum 1200 mg/day or betaxolol : 5-20 mg orally once daily or bisoprolol : 2.5 to 10 mg orally once daily, maximum 20 mg/day or carvedilol : 6.25 mg orally (immediate-release) twice daily initially, increase to 12.5 mg twice daily after 1-2 weeks, maximum 50 mg/day given in 2 divided doses or labetalol : 100-400 mg orally twice daily, maximum 2400 mg/day given in 2-3 divided doses or metoprolol : 50 mg orally (regular-release) twice daily initially, increase at weekly intervals to maximum 100-450 mg/day given in 2-3 divided doses or nebivolol : 5 mg orally once daily initially, increase at 2-week intervals, maximum 40 mg/day or propranolol : 40 mg orally (immediate-release) twice daily initially, increasing to maximum 640 mg/day as tolerated Secondary Options losartan : 25-100 mg orally once daily or in 2 divided doses or olmesartan : 20-40 mg orally once daily

Treatment Patient group no comorbidity (other than osteoporosis): non-pregnant line Treatmenthide all

or telmisartan : 20-80 mg orally once daily or valsartan : 80-320 mg orally once daily or in 2 divided doses -- AND -acebutolol : 200-800 mg orally given once daily or in 2 divided doses, maximum 1200 mg/day or betaxolol : 5-20 mg orally once daily or bisoprolol : 2.5 to 10 mg orally once daily, maximum 20 mg/day or carvedilol : 6.25 mg orally (immediate-release) twice daily initially, increase to 12.5 mg twice daily after 1-2 weeks, maximum 50 mg/day given in 2 divided doses or labetalol : 100-400 mg orally twice daily, maximum 2400 mg/day given in 2-3 divided doses or metoprolol : 50 mg orally (regular-release) twice daily initially, increase at weekly intervals to maximum 100-450 mg/day given in 2-3 divided doses or nebivolol : 5 mg orally once daily initially, increase at 2-week intervals, maximum 40 mg/day or propranolol : 40 mg orally (immediate-release) twice

Treatment Patient group no comorbidity (other than osteoporosis): non-pregnant line Treatmenthide all

daily initially, increasing to maximum 640 mg/day as tolerated

concomitant atrial fibrillation without other comorbidity: nonpregnant

1st

beta-blocker monotherapy + lifestyle modification

Non-selective beta-blockers include carvedilol (also has alpha-blocking properties), labetalol, penbutolol, pindolol, propranolol, and timolol.

Beta-1-selective blockers include acebutolol, atenolol, betaxolol, bisoprolol, and metoprolol. Following abrupt cessation of therapy with certain beta-blocking agents, exacerbations of angina pectoris and, in some cases, MI have occurred. All beta-blockers should be weaned over 1 to 2 weeks and patients should be monitored for symptoms of angina. Atenolol is generally less cardioprotective and has less BP-lowering effects compared with other members of this class.[100]

Calcium-channel blockers may be preferred to betablocker in COPD or asthma. The lowest dose should be titrated upwards until a therapeutic effect is achieved or an adverse effect limits further titration.

Evidence from post hoc analyses suggested that angiotensin receptor antagonists or ACE inhibitors did not prevent the occurrence [75] [76] or the recurrence [77] [78] of atrial fibrillation. Further intervention trials are necessary; results of metaanalysis of previous trials are pending. Primary Options acebutolol : 200-800 mg orally given once daily or in 2 divided doses, maximum 1200 mg/day

Treatment Patient group no comorbidity (other than osteoporosis): non-pregnant line Treatmenthide all

OR betaxolol : 5-20 mg orally once daily OR bisoprolol : 2.5 to 10 mg orally once daily, maximum 20 mg/day OR carvedilol : 6.25 mg orally (immediate-release) twice daily initially, increase to 12.5 mg twice daily after 1-2 weeks, maximum 50 mg/day given in 2 divided doses OR labetalol : 100-400 mg orally twice daily, maximum 2400 mg/day given in 2-3 divided doses OR metoprolol : 50 mg orally (regular-release) twice daily initially, increase at weekly intervals to maximum 100-450 mg/day given in 2-3 divided doses OR nebivolol : 5 mg orally once daily initially, increase at 2-week intervals, maximum 40 mg/day OR propranolol : 40 mg orally (immediate-release) twice daily initially, increasing to maximum 640 mg/day as tolerated Secondary Options atenolol : 25-100 mg orally once daily
2nd

non-dihydropyridine CCB + lifestyle modification

Non-dihydropyridine calcium-channel blockers (CCBs) (verapamil or diltiazem) are associated with

Treatment Patient group no comorbidity (other than osteoporosis): non-pregnant line Treatmenthide all

negative inotropy and slowing of AV conduction.


Frequently used in the treatment of SVT or atrial arrhythmias/rapid ventricular response. Avoid in people with decreased ejection fraction. The lowest dose should be titrated upwards until a therapeutic effect is achieved or an adverse effect limits further titration.

Evidence from post hoc analyses suggested that angiotensin receptor antagonists or ACE inhibitors did not prevent the occurrence [75] [76] or the recurrence [77] [78] of atrial fibrillation. Further intervention trials are necessary; results of metaanalysis of previous trials are pending. Primary Options diltiazem : 120-240 mg orally (extended-release) once daily OR verapamil : 120-240 mg orally (sustained-release) once daily, maximum 480 mg/day given in 2 divided doses

concomitant benign prostatic hypertrophy without other comorbidity

1st

alpha-blocker + lifestyle modification


If CAD or CHF present, favour preferred drugs for those conditions. Selective blockade at the alpha-1 receptor promotes vasodilation and has a hypotensive effect. Alpha-blockers were associated with an increased development of CHF symptoms in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) trial. [92]

Treatment Patient group no comorbidity (other than osteoporosis): non-pregnant line Treatmenthide all

May be associated with profound first-dose hypotension. Initial dosing should begin with the lowest dose possible and be titrated up slowly. Primary Options doxazosin : 1-16 mg orally (immediate-release) every evening OR prazosin : 1 mg orally two to three times daily initially, increasing to 6-15 mg/day given in 2-3 divided doses, maximum 20 mg/day OR terazosin : 1-10 mg orally once daily or in 2 divided doses, maximum 20 mg/day

concomitant Raynaud's disease, PVD, coronary, or spasm without other comorbidity: nonpregnant

1st

dihydropyridine CCB + lifestyle modification


Dihydropyridine calcium-channel blockers (CCBs) are peripheral vasodilators. The lowest dose should be titrated upwards until a therapeutic effect is achieved or an adverse effect limits further titration. Primary Options amlodipine : 2.5 to 10 mg orally once daily OR felodipine : 2.5 to 10 mg orally once daily, maximum 20 mg/day OR isradipine : 2.5 to 10 mg/day orally given in 2 divided doses

Treatment Patient group no comorbidity (other than osteoporosis): non-pregnant line Treatmenthide all

OR nicardipine : 20-40 mg orally (regular-release) three times daily OR nifedipine : 30-60 mg orally (extended-release) once daily OR nisoldipine : 20 mg orally once daily, maximum 60 mg/day

refractory/resistant to optimised triple therapy at any stage: nonpregnant without CHF

1st

ACE inhibitor/angiotensin-II receptor blocker + thiazide + CCB + beta-blocker + lifestyle modification

A combination of up to 4 agents, ACE inhibitors/angiotensin-II receptor blockers, thiazide, calcium-channel blockers (CCBs), and betablockers (quadruple therapy), may be required.

Following abrupt cessation of therapy with certain beta-blocking agents, exacerbations of angina pectoris and, in some cases, MI have occurred. All beta-blockers should be weaned over 1 to 2 weeks and patients should be monitored for symptoms of angina.

Dihydropyridine CCBs are peripheral vasodilators. Avoid combination of non-dihydropyridine CCB (verapamil or diltiazem) plus beta-blocker, because of potential bradycardia or AV block.

The lowest dose should be titrated upwards until a therapeutic effect is achieved or an adverse effect limits further titration.

2nd

hydralazine added to 3 agents

Second-line alternative to quadruple therapy with

Treatment Patient group no comorbidity (other than osteoporosis): non-pregnant line Treatmenthide all

more commonly used agents.

Added to 3 out of 4 of: ACE inhibitors/angiotensin-II receptor blockers, thiazide, calcium-channel blockers, or beta-blockers.

May also be used in CHF. The lowest dose should be titrated upwards until a therapeutic effect is achieved or an adverse effect limits further titration. Primary Options 3 out of 4 of: ACE inhibitors/angiotensin-II receptor blockers, thiazide, calcium-channel blockers or beta-blockers and hydralazine : 25 mg orally twice daily initially, titrate dose at weekly intervals to minimum effective dose, maximum 200 mg/day

2nd

clonidine added to 3 agents


Second-line alternative to quadruple therapy with more commonly used agents. Added to 3 out of 4 of: ACE inhibitors/angiotensin-II receptor blockers, thiazide, calcium-channel blockers, or beta-blockers.

The lowest dose should be titrated upwards until a therapeutic effect is achieved or an adverse effect limits further titration. Primary Options 3 out of 4 of: ACE inhibitors/angiotensin-II receptor blockers, thiazide, calcium-channel blockers or

Treatment Patient group no comorbidity (other than osteoporosis): non-pregnant line Treatmenthide all

beta-blockers and clonidine : 0.1 mg orally twice daily; maximum 2.4 mg/day; 0.1 mg/24 hours patch every 7 days, may increase by 0.1 mg every 1-2 weeks, maximum 0.6 mg/24-hour patch once weekly
2nd

alpha-blocker added to 3 agents


Second-line alternative to quadruple therapy with more commonly used agents. Added to 3 out of 4 of: ACE inhibitors/angiotensin-II receptor blockers, thiazide, calcium-channel blockers, or beta-blockers. Primary Options 3 out of 4 of: ACE inhibitors/angiotensin-II receptor blockers, thiazide, calcium-channel blockers or beta-blockers -- AND -doxazosin : 1-16 mg orally (immediate-release) every evening or prazosin : 1 mg orally two to three times daily initially, increasing to 6-15 mg/day given in 2-3 divided doses, maximum 20 mg/day or terazosin : 1-10 mg orally once daily or in 2 divided doses, maximum 20 mg/day

2nd

minoxidil added to 3 agents

Treatment Patient group no comorbidity (other than osteoporosis): non-pregnant line Treatmenthide all

Second-line alternative to quadruple therapy with more commonly used agents. Added to 3 out of 4 of: ACE inhibitors/angiotensin-II receptor blockers, thiazide, calcium-channel blockers, or beta-blockers.

Most patients require a loop diuretic, because of fluid retention. However, when loop diuretics are added, thiazides are discontinued because of risk of hypokalaemia.

The lowest dose should be titrated upwards until a therapeutic effect is achieved or an adverse effect limits further titration. Primary Options 3 out of 4 of: ACE inhibitors/angiotensin-II receptor blockers, diuretic, calcium-channel blockers or betablockers and minoxidil : 2.5 to 80 mg orally once daily or in 2 divided doses

2nd

aliskiren added to 3 agents


Second-line alternative to quadruple therapy with more commonly used agents. Added to: thiazide diuretic, calcium-channel blocker, and a beta-blocker. Aliskiren is a direct renin inhibitor, whose precise mechanism of action is not yet known. [84] [85] The role of aliskiren in the treatment of HTN is not well defined. However, studies suggest that BP lowering is comparable (or possibly even superior) to that of

Treatment Patient group no comorbidity (other than osteoporosis): non-pregnant line Treatmenthide all

ACE inhibitors [86] and that it is safe and effective as monotherapy. Until recently, it was recommended for use in combination with ACE inhibitors or angiotensin-II receptor blockers; however, in December 2011 the manufacturer recommended that physicians should no longer prescribe aliskiren-containing products with these two classes of drugs based on the results, and subsequent early termination, of the ALTITUDE trial. The trial was testing the effect of aliskiren (in combination with ACE inhibitors or angiotensin-II receptor blockers) in type 2 diabetics at high risk for cardiovascular and renal events, and found an increased risk for non-fatal stroke, renal complications, hyperkalaemia, and hypotension in patients taking the drug for 18-24 months. The US FDA now recommends that the combination of aliskiren with ACE inhibitors or angiotensin-II receptor blockers is contra-indicated in patients with diabetes because of the risk of renal impairment, hypotension, and hyperkalaemia. It also recommends that this combination of drugs be avoided in patients with moderate to severe renal impairment (i.e., GFR <60 mL/min).

The lowest dose should be titrated upwards until a therapeutic effect is achieved or an adverse effect limits further titration. Primary Options thiazide, calcium-channel blocker and beta-blocker and

Treatment Patient group no comorbidity (other than osteoporosis): non-pregnant line Treatmenthide all

aliskiren : 150-300 mg orally once daily

pregnant

1st

methyldopa + lifestyle modification


Stimulates central alpha-2 receptors that have a sympatholytic effect on the vasculature. Role in the US has largely been relegated to use in pregnancy, given its historical tolerability in pregnant patients, but generally myriad adverse effects.[101]

The lowest dose should be titrated upwards until a therapeutic effect is achieved or an adverse effect limits further titration. Primary Options methyldopa : 250 mg orally two to three times daily initially, adjust dose every 2 days if necessary, maximum 3000 mg/day

2nd

labetalol + lifestyle modification

The lowest dose should be titrated upwards until a therapeutic effect is achieved or an adverse effect limits further titration. Primary Options labetalol : 100 mg orally twice daily, maximum 2400 mg/day given in 2-3 divided doses

Ongoing

Treatment approach
The main goal of treatment is to decrease the risk of mortality and of cardiovascular and renal morbidity. [4] BP goal should be less than 130/80 mmHg in patients with renal disease, and less than 140/90 mmHg in all other

patients. Regarding patients with concomitant diabetes mellitus, there is good-quality evidence that very intensive BP lowering (targeting a systolic pressure <120 mmHg, as compared with targeting <140 mmHg) does not lessen risk (composite outcome: non-fatal MI, non-fatal stroke, or death from cardiovascular cause) and may increase risk of adverse events. [5] Older patients should be treated with antihypertensive therapy with a goal target BP of 140/90 mmHg, as is the goal in the general population. However, because of differences in the general health of very old patients, the decision to treat should be on an individual basis, and BP lowering should be gradual and carefully monitored by the physician. [3] [49]

Lifestyle modification
The initial approach to a newly diagnosed patient should include a thorough explanation of the risks associated with HTN and the need for adequate control and adherence to therapy. Initial therapeutic measure should be lifelong lifestyle modification including: [50] [36] [51] [6] [52]

Sodium reduction (<2 g/day)[B Evidence] Dietary Approaches to Stop Hypertension (DASH) diet (3 servings of fruit and vegetables daily, whole grains, low sodium, low-fat proteins)

Weight loss to BMI under 30 kg/m^2 Increased physical activity: 3 to 5 times/week of daily aerobic exercise for 30- to 50-minute sessions as tolerated Limited alcohol consumption (<7 drinks/week for men, <5 drinks/week for women).

Advice about lifestyle modification should be given upon diagnosis and should continue concurrently with all other therapeutic measures. Prior to initiation of an exercise programme, patients should discuss a plan with their healthcare provider. Smoking cessation should always be encouraged as well, to promote general vascular health, though smoking cessation has not been associated with decreased BP. A 3-month trial is recommended in compliant patients willing to make therapeutic lifestyle changes, prior to determining that pharmacological therapy is necessary. Most patients will require drug therapy to achieve target BP control.

Drug therapy for stage 1

For stage 1 HTN (BP 140 to 159/90 to 99 mmHg) monotherapy can be initiated. The choice of antihypertensive agent is driven by efficacy, adverseeffect profile, and cost. [C Evidence] Many people with stage 1 HTN have a constellation of other cardiovascular risk factors such as smoking or mild dyslipidaemia that increase the importance of aggressive BP lowering. Alternatively, a low dose of two drugs can be used initially. Evidence does not favour one or the other approach. [2] Generally, when an ACE inhibitor would usually be chosen but is not tolerated, an angiotensin-II receptor blocker can be substituted. If BP cannot be controlled with a single agent, a drug from a different class of antihypertensives is added.

Stage 1 HTN, no comorbidity (other than osteoporosis)


Thiazide-type diuretics have been shown to be safe and efficacious first-line therapy. They also decrease renal calcium excretion, so are a good choice for women with osteoporosis. As with all antihypertensive medications, the initial dose should be the lowest possible, and then titrated for a therapeutic effect, while observing for potential adverse effects. The non-thiazide (thiazide-like) diuretic indapamide is a less-preferred alternative. First choice for add-on treatment is an ACE inhibitor.

Comorbid CAD
Beta-blockers are first-line. Beta-blockers have proven beneficial in patients with chronic stable angina, post-MI, or CHF, in patients with CAD undergoing surgery, or in patients with hypertrophic obstructive cardiomyopathy. [53] [54] [55] [56] [57] Many patients with CAD also take nitrates, which act as an exogenous nitric oxide (NO) donor. Modest reductions in systolic BP can be observed, but the FDA has not approved the use of nitrates solely as antihypertensive therapy. [15] ACE inhibitors have been shown in some trials to decrease cardiovascular events, while other studies have not demonstrated a benefit for ACE inhibitor in the setting of stable CAD with normal LV function. [58] [59] [60]

Comorbid CHF

In patients with comorbid CHF, ACE inhibition (angiotensin-II receptor blocker if not tolerated) plus subsequent beta-blockade and aldosterone antagonism is used. ACE inhibition has been shown to convey a survival advantage in patients with CHF. [61] [54] Angiotensin-II receptor blockers also decrease morbidity and mortality. [62] [63] Compared with ACE inhibitors, angiotensin-II receptor blockers were equivalent, but not superior, in the treatment of patients with CHF. [64] [65] Beta-blockers have proven mortality benefits in patients with chronic CHF. [55] [56] Aldosterone receptor blockers should be given to patients with heart failure and ejection fraction under 35%, taking optimised ACE inhibitor/angiotensin-II receptor blocker and beta-blocker treatment, who still require antihypertensive therapy. Blockade of aldosterone has been associated with decreased end-organ fibrosis. [66] Diuretics (non-aldosterone) confer no mortality benefit for patients with CHF. However, they are frequently used to relieve symptoms of fluid overload. The combination of hydralazine and nitrates has been shown to be of benefit for black patients already taking ACE inhibitors, beta-blockers, and aldosterone antagonists, as well as in all patients with CHF intolerant of both ACE inhibitors and angiotensin-II receptor blockers. [67][68]

Comorbid LVH, diabetes, or renal disease


An ACE inhibitor is first choice for comorbid diabetes and renal disease, and an angiotensin-II receptor blocker is first choice for comorbid LVH. ACE inhibition has proven beneficial across a myriad of cardiovascular disease states including CHF, LVH, and diabetes. [58] [59]Furthermore, ACE inhibitors are renoprotective, decreasing the progression of proteinuria in diabetic patients. [69] Angiotensin-II receptor blockers have been shown to decrease morbidity and mortality in patients with HTN and LVH. [62] Sleep-time BP is the most significant independent prognostic marker of cardiovascular events in diabetes. Importantly, the decrease in asleep blood pressure - a novel therapeutic target requiring evaluation by ambulatory monitoring - has been shown to be the most significant independent predictor of event-free survival in diabetic patients. [70] [71] [72] [73] [74]

Comorbid atrial fibrillation

First choice is a beta-blocker. Second choice is a non-dihydropyridine calcium-channel blocker (CCB). Evidence from post-hoc analyses suggest that angiotensin receptor antagonists or ACE inhibitors do not prevent the occurrence [75] [76] or the recurrence [77] [78] of atrial fibrillation. In one randomised control trial, irbesartan, an angiotensin-II receptor blocker, failed to show a reduction in cardiovascular events in patients with atrial fibrillation. [79] However, a subsequent randomised controlled trial has shown that telmisartan, another angiotensin-II receptor blocker, is more effective than ramipril, an ACE inhibitor, and amlodipine, a CCB, in reducing atrial fibrillation recurrence and severity. [80] [81] This could be related to a specific effect of telmisartan on atrial electric remodelling. Further intervention trials are necessary; results of meta-analysis of previous trials are pending.

Comorbid benign prostatic hypertrophy


This is the only group for whom an alpha-blocker is first choice of agent.

Comorbid Raynaud's disease, PVD, or coronary artery spasm


Dihydropyridine CCBs are first choice. In addition to vascular disease, CCBs are also useful for persistent angina or stroke prevention. [82] [83]

Stage 2 HTN
Patients presenting with stage 2 HTN (BP >160/100 mmHg) will probably require more than one drug for BP control. Therefore, the initiation of two concurrent antihypertensive medications is recommended. After titrating dosage, several combination pills are available for convenience. The combination of non-dihydropyridine CCBs with beta-blockers should be avoided, because of an increased risk of high-degree AV block.

Recalcitrant (resistant) HTN


Recalcitrant HTN is a true management challenge. Frequently requiring multiple antihypertensive agents, patients must be observed and counselled regarding adverse effects, medication adherence, potential drug-drug interactions, and metabolic abnormalities. Patients should be screened for secondary causes of HTN. Treatment often involves the use of less commonly prescribed antihypertensives (hydralazine, clonidine, minoxidil,

alpha-blocker), which have multiple adverse effects. The choice of less commonly prescribed antihypertensives, much like other antihypertensives, should be based on patients' comorbidities and ability to tolerate the treatment. Aliskiren is a direct renin inhibitor, whose precise mechanism of action is not yet known. [84][85] The role of aliskiren in the treatment of HTN is not welldefined. However, studies suggest that BP lowering is comparable (or possibly even superior) to that of ACE inhibitors [86] and that it is safe and effective as monotherapy. Until recently, it was recommended for use in combination with ACE inhibitors or angiotensin-II receptor blockers; however, in December 2011 the manufacturer recommended that physicians should no longer prescribe aliskiren-containing products with these two classes of drugs based on the results, and subsequent early termination, of the ALTITUDE trial. The trial was testing the effect of aliskiren (in combination with ACE inhibitors or angiotensin-II receptor blockers) in type 2 diabetics at high risk for cardiovascular and renal events, and found an increased risk for non-fatal stroke, renal complications, hyperkalaemia, and hypotension in patients taking the drug for 18-24 months. The US FDA now recommends that the combination of aliskiren with ACE inhibitors or angiotensin-II receptor blockers is contra-indicated in patients with diabetes because of the risk of renal impairment, hypotension, and hyperkalaemia. It also recommends that this combination of drugs be avoided in patients with moderate to severe renal impairment (i.e., GFR <60 mL/min). Hydralazine preferentially vasodilates peripheral arterioles, decreasing peripheral vascular resistance. [87] Minoxidil is a potent vasodilator that promotes fluid retention and a sympathetic surge. Most patients will require the co-administration of diuretics and sympathetic blockade. [88] Minoxidil should be reserved for hypertensive patients who do not respond adequately to maximum therapeutic doses of a diuretic and two other antihypertensive agents. Clonidine stimulates central alpha-2 receptors that have a sympatholytic effect on the vasculature.

Pregnancy
Choice of therapy in pregnancy is usually alpha-methyldopa or labetalol.

The elderly
In very elderly patients, many physicians are reluctant to treat HTN in accordance with the BP goal of less than 140/90 mmHg, for a number of

reasons, including concerns about fall risk, drug interactions, adverse effects, and lack of benefit in mortality reduction. Few studies have evaluated hypertension in this population, and studies that included patients over the age of 80 enrolled too few to draw robust conclusions. Studies to date have demonstrated reductions in stroke, heart failure, and cardiovascular events in the very elderly without reaching mortality benefit. [89] [90] The American College of Cardiology Foundation/American Heart Association have published guidelines that suggest treating the very elderly carefully and with different BP goals from those previously recommended. [91] These guidelines recommend that medication be initiated at the lowest dose with gradual increments as tolerated. If BP remains uncontrolled, a second drug from a different class should be added. The recommended target BP is lower than 140/90mm Hg, with a systolic BP between 140 and 145 mmHg, in persons 80 years and older, if tolerated.

Emerging treatments
Renal sympathetic denervation for treatment-resistant hypertension Previously employed approaches used to reduce blood pressure in patients with severe HTN include renal sympathectomy, which has since been abandoned in usual practice due to its significant side effects. [102] [103] [104] However, activation of renal sympathetic nerves remains key to the pathogenesis of essential HTN and catheter-based radiofrequency ablation of the renal sympathetic nerves has been shown to lower blood pressure in patients with resistant HTN. The Symplicity HTN-2 trial enrolled 106 patients with treatment-resistant hypertension. Participants were randomised to undergo renal denervation with previous treatment or to maintain previous treatment alone (control group). The renal denervation group had impressive mean office BP reduction of 20/7, 24/8, and 32/12 mmHg by 1, 3, and 6 months following denervation, respectively. There was no BP reduction in the control group. No serious procedure- or device-related complications were reported. [105] The upcoming Symplicity HTN-3 study is expected to enrol 530 patients and will provide further data on the catheterbased renal denervation procedure. [106] The European Society of Hypertension advocates the use of renal denervation but recommends that it should only be used in patients with truly drug-resistant hypertension and must only be performed in very experienced centres. [107] Baroreflex activation therapy

Electrical stimulation of the carotid sinus baroreflex system, also known as baroreflex activation therapy (BAT), may decrease blood pressure in patients with resistant hypertension. Electric stimulators directly activating afferent baroreflex nerves have previously failed in trials for technical reasons. However, a novel implantable device may overcome some of the previously experienced technical problems. The device stimulates the carotid sinus wall and has been shown to reduce BP in feasibility studies. [108] [109] [110] In the Rheos Pivotal trial, which assessed long-term blood pressure control in resistant-hypertension patients receiving BAT, blood pressure reduction was maintained over long-term follow-up of 22 to 53 months. [111] L-arginine supplementation Oral supplementation with L-arginine, an amino acid and a substrate of nitric oxide synthase, has been shown to significantly lower both systolic and diastolic BP. [112] Vitamin C supplementation Vitamin C supplementation has been shown to reduce systolic and diastolic BP in short-term trials. Long-term trials examining the effects of vitamin C supplementation on BP and clinical events are needed. [113]

Monitoring
While adjusting medication dosage, BP should be monitored every 2 to 4 weeks. Once stabilised, BP should be checked and medications reviewed every 3 months. Serum potassium and creatinine should be checked at least twice yearly.

Patient Instructions
As with most chronic conditions, HTN requires a lifelong commitment from both patient and physician to pursue aggressive management with healthy lifestyle choices and medical therapy. Patients should be counselled about diet (Dietary Approaches to Stop Hypertension [DASH]), sodium <2 g/day, in consultation with a nutritionist).
Smoking raises BP acutely and transiently, but long-term studies have not found an association between smoking and the risk of developing chronic HTN. [125] Nevertheless, smoking cessation should be encouraged to reduce cardiovascular risk. Acute consumption of coffee and black tea has a mild pressor effect; however, long-term studies have found slightly lower BP in patients who consume caffeine daily. [126] [52]Therefore, moderate caffeine consumption is acceptable.

Patients should be advised to begin and maintain aerobic exercise as tolerated, with a goal of sessions 30 to 50 minutes 3 to 5 days/week.

Medication adherence is important and it should be discussed with patients in whom drug therapy for HTN is often a lifelong commitment.

Complications
Complicationhide all

coronary artery disease see our comprehensive coverage of Overview of acute coronary syndrome For every 20/10 mmHg increase in BP, there is a lifetime doubling of mortality related to ischaemic heart disease or CVA. [115] As with all other associated complications and comorbid diseases, aggressive BP control, along with therapy specific for the individual condition, may retard the progression of disease. cerebrovascular accident see our comprehensive coverage of Overview of stroke The risk of developing CVA varies linearly with BP, and BP control reduces the risk of recurrent CVA. [116] left ventricular hypertrophy (LVH) LVH on echocardiography is seen in more than 30% of hypertensive patients. [120] Linked to cardiovascular morbidity and mortality. [121] LVH patterns vary based on haemodynamical loading conditions. [122] congestive heart failure see our comprehensive coverage of Chronic congestive heart failure Patients with HTN are 3 times more likely to develop CHF (systolic or diastolic dysfunction) as are normotensive patients. [117] ACE inhibitors, angiotensin-II receptor antagonists, and beta-blockers confer a mortality benefit. Diuretics do not, but loop diuretics are frequently used to relieve symptoms of fluid overload. Blockade of aldosterone has been associated with decreased end-organ fibrosis. [66] retinopathy HTN is associated independently with retinopathy. HTN is also a major risk factor for development of other retinal vascular diseases, such as retinal vein or artery occlusion, or ischaemic optic neuropathy. aortic dissection see our comprehensive coverage of Aortic dissection More than 70% of patients with aortic dissection have a history of HTN. Despite improved methods of diagnosis and increased awareness, aortic dissection remains associated with

high mortality rates, particularly proximal (type A) dissections. [118] [119] peripheral artery disease see our comprehensive coverage of Peripheral vascular disease Treatment of HTN in patients with peripheral artery disease reduces the risk of MI, stroke, or CHF. renal failure see our comprehensive coverage of Chronic renal failure HTN is closely associated with the development of renal disease and end-stage renal disease(ESRD). However, while many hypertensive patients will develop a mild degree of nephrosclerosis, few progress to ESRD. [123] A more malignant course of hypertensive kidney disease is seen in black than in white people. [124]

Prognosis
Several trials have shown that uncontrolled HTN is a major risk factor for the development of cardiac, vascular, renal, and cerebrovascular disease, morbidity, and mortality. However, even modest reductions in BP decrease morbidity and mortality. [1] In clinical trials, treatment of HTN to achieve goals of BP less than 130/80 mmHg for patients with diabetes or renal disease, or BP less than 140/90 mmHg for all others has been associated with lifetime reductions of 35% for stroke, 20% for CAD, and 50% for CHF. [114] Further studies are needed to confirm optimal BP targets in diabetes. In one randomised clinical trial (ACCORD) a more stringent blood pressure goal for patients with type 2 diabetes did not significantly reduce the primary cardiovascular outcome or most secondary outcomes compared with standard blood pressure goals. In this study, the number of total and non-fatal strokes was lower in the intensive therapy group, although the clinical benefit was limited (number needed to treat [NNT] = 89 for 5 years to prevent one stroke). [5]