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Lecture 2

Not All Betablockers Are the Same


The Role of Betablockers in

the Treatment of Hypertension


PREFERRED DRUGS

Preferred drugs for coronary

artery disease

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Hypertension and CAD

Williams B, et al. Eur Heart J 2018. doi:10.1093/eurheartj/ehy339


PREFERRED DRUGS

Preferred drugs for heart failure

with reduced ejection fraction*

* EF ≤40%
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Hypertension and HFrEF

Williams B, et al. Eur Heart J 2018. doi:10.1093/eurheartj/ehy339


PREFERRED DRUGS

Preferred drugs for atrial

fibrillation

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Hypertension and atrial
fibrillation

Williams B, et al. Eur Heart J 2018. doi:10.1093/eurheartj/ehy339


Preferred drugs for
uncomplicated hypertension, DM,
Stroke/TIA, PAD, or with HMOD,

DM = diabetes mellitus
TIA = transient ischemic attack
PAD = peripheral artery disease
HMOD = hypertension mediated organ damage
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PREFERRED DRUGS

Preferred drugs for chronic

kidney disease

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Hypertension and CKD

Williams B, et al. Eur Heart J 2018. doi:10.1093/eurheartj/ehy339


IS TREATMENT WITH BETA BLOCKERS
ASSOCIATED WITH RISK OF
NEW ONSET OF DIABETES?

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Comparative Incidence of New-Onset
Diabetes with Antihypertensive Agents in Clinical Trials
Study Treatments Duration New-onset P-value
(years) diabetes (%)
CAPP ACE-I vs 6.1 6.5 vs 7.3 <0.05
-blocker/diuretic

HOPE ACE-I vs placebo 4.5 3.6 vs 5.4 <0.001


ALLHAT ACE-I vs CCB vs 4.9 8.1 vs 9.8 vs <0.05
diuretic 11.6
SCOPE ARB vs diuretic 3.7 4.9 vs 6.0 0.09

LIFE ARB vs -blocker 4.8 6.0 vs 8.0 <0.001

ALPINE ARB vs diuretic/ - 1.0 0.5 vs 4.1 <0.05


blocker
CHARM ARB vs conventional 1.6 6 vs 7 <0.02
therapy
VALUE ARB vs CCB 5.5 13.1 vs 16.4 <0.0001
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ASCOT-BPLA:
Cumulative Incidence of New-Onset Diabetes Mellitus

10 Atenolol-based regimen
Proportion of new-onset diabetes

Amlodipine-based regimen
8

2 HR 0.70
mellitus

p<0.0001
0
0 1 2 3 4 5 6

Time (years)

Dahlöf B, et al for the ASCOT investigators. Lancet 2005; 366: 895–906


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ESH/ESC: Antihypertensive Treatment Preferred Drug
- ACE Aldo-
Diuretic ARB CCB
blocker inhibitor antagonist

Asymptomatic
• •
atherosclerosis

Microalbuminuria
• •
LVH • • •
ISH (elderly)
• •
Mets • • •
Pregnancy CCB, ß-blocker (labetolol), methyldopa
Mancia G, et al. 2007 ESH/ESC Guidelines for the Management of Arterial Hypertension.
J Hypertens 2007;25:1105-1187
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BRIDGING THE GAP

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Distribution of Adrenoceptors and The Physiologic Effects of Stimulation

Predominant
Organ Physiological effect of stimulation
adrenoceptor

Myocardium 1>2  Contractility and heart rate

Smooth muscle: bronchi 2 Bronchodilatation

1 Vasodilatation (coronary)
Smooth muscle: blood vessels
2 Vasodilatation

Fat tissue 2>1 Stimulation of lipolysis

Liver 2 Glycogenolysis and gluconeogenesis

Pancreas 2 Stimulation of insulin release

Skeletal muscle 2 Increase in tremor

Blood lipids 2 Low TG and high HDL

Kidney 1  Renin release

Eye 2  Intraocular pressure

14 Cruickshank JM, Prichard BNC. 1994


1/2 Selectivity Ratios

75/1
1/2 Selectivity Ratios

35/1 35/1
20/1
1/2

Propranolol Atenolol Bisoprolol


-1/25
Metoprolol Betaxolol

-1/50

-1/300
ICI
118,551

Wellstein A, et al. J Cardiovasc Pharmacol 1986;8(Suppl):S36-40


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Low Beta2 Blockade
By High -Dose Bisoprolol
Some beta-blockers improve arterial compliance
Non-desirable properties for Desirable properties for improving compliance
improving compliance
Beta-2 blockade Alpha-blockade Beta-2 ISA Absence of beta-2
blockade i.e. high beta-1
selectivity
Strong Weak
e.g. Propranolol e.g. Atenolol e.g. Labetalol (but e.g. Pindolol, e.g. Bisoprolol (at doses up
(tends to actually (tends to be problems with Bopindolol, to 10 mg, 0-5% of beta-2
decrease neutral in its postural hypotension Celiprolol, Nebivolol receptors blocked)
compliance i.e. effect on and skin (but high ISA a) can
stiffens arterial wall) compliance; at vasodilatation) cause tremor and
dose 100 mg a palpitations b)
day diminishes beneftis
approximately of beta-1 blockade
25% of beta-2 i.e. in heart failure
receptors are and coronary heart
blocked) disease)
ISA = Intrinsic sympathomimetic activity

Cruickshank JM. Int J Cardiol 2007;120:10–27


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TAKE-HOME MESSAGE

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TAKE-HOME MESSAGE
Despite its potential effect on the development
of new-onset diabetes, betablockers may be
used in most hypertension patients with
cardiac diseases. Therefore, choosing a best
betablocker is required.

Based on its pharmacodynamic properties,


beta-blockers with high beta1 selectivity like
bisoprolol may cause less side effect on the
development of new-onset diabetes even
when used in high dose.
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