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

23
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%
23
Hypertension and HFrEF

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

 PREFERRED DRUGS

Preferred drugs for atrial

fibrillation

23
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

23
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?

7
 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
8
 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

9
 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
11
 BRIDGING THE GAP

13
 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

15
 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

16
 TAKE-HOME MESSAGE

17
 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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