Launching oleh Dr. Hendro

1. BETA BLOCKER USE IN
CARDIOVASCULAR DISEASES
Dr. dr. Hendro Darmawan, SpJP,
FIHA
PIT VI IDI Kota Bogor, 9 Nopember
2013

2. CVD (focused on) :

3. Classification of β-blockers
Table 6: Classification of ß-blockers
1st Generation
Non-selective
Propranolol
2nd Generation
β1-selective
Atenolol
Metoprolol
Betaxolol
Bisoprolol
3rd Generation
Additional
properties, for
example
vasodilation
Carvedilol
Nebivolol

4. 1-selectivity of various blockers
Bisoprolol
1:75
Atenolol
Betaxolol
1:35
1:35
Metoprolol
increasing
ß 1-selectivity
1:20
no
selectivity
1.8:1
Propranolol
increasing
ß 2-selectivity
300:1
ICI
118.551
Ratio of constants of inhibition
Wellstein A et al. J Cardiovasc Pharmacol 1986; 8 (Suppl. 11): 36-40
Wellstein A et al. Eur Heart J 1987; 8 (Suppl. M): 3–8

5. Beta 1 VS Beta 2 Selectivity

6. Elimination routes of various beta
blockers from body

8. MECHANISM OF BETA BLOCKERS
IN HEART FAILURE
 Upregulation of β receptors and improved β





adrenergic signaling.
Reducing the hyperphosphorylation of calcium
release channels of sarcoplasmic reticulum and
normalizing their function
Bradycardia (↑ coronary blood flow and
decreased myocardial oxygen demand).
Protection from catecholamine myocyte toxicity.
Suppression of ventricular arrhythmias.
Anti-apoptosis. β2 receptors, which are relatively
increased, are coupled to inhibitory G protein & block
apoptosis.

20. Mechanism of β-blocker benefits
in ischemic heart disease
• Reduction in myocardial oxygen
requirements via a decrease in
heart rate, blood pressure and
ventricular contractility.
• Slowing of the heart rate
prolongs coronary diastolic
filling period.
• Redistribution of coronary

21. Mechanism of β-blocker benefits
in ischemic heart disease
• Increases threshold to
ventricular fibrillation.
• Reduction in infarct size and
reduction in the risk of cardiac
rupture.
• Reduction in the rate of
reinfarction.
• Regression of the atheromatous

22. Summary of Trials of Beta-Blocker Therapy
Phase of
Treatment
Total No.
Patients
RR (95% CI)
Acute
treatment
28,970
0.87 (0.77-0.98)
Secondary
prevention
24,298
0.77 (0.70-0.84)
Overall
53,268
0.81 (0.75-0.87)
2
1
0.5
Relative risk (RR) of death
Placebo
Beta blocker
better
better
Antman E, Braunwald E. Acute Myocardial Infarction. In:
Braunwald E, Zipes DP, Libby P, eds. Heart Disease: A
textbook of Cardiovascular Medicine, 6th ed.,
Philadelphia, PA: W.B. Sanders, 2001, 1168.

23. MAINTATE
Usefulness of beta-blocker therapy in patients with
diabetes mellitus and CAD (BIP)
1.00
0.90
0.85
Mortality
42%
Withß-blockers
Withoutß-blockers
0.80
P = 0.0001
0.75
1
14.417 pts
2
3
Year
4
5
Jonas et al. Am J Cardiol 1996; 77: 1273 et seqq.
Survival rate
0.95

25. BP and -BLOCKERS
Central
effects
Baroreceptor
reflexes

Carotid sinus
?
Stellate
ganglion
NE


E

Renin

Sinus rate
Stroke volume
Cardiac output
Terminal
neurone
Angio I
Angio II
Systemic
vascular
resistance
NE

Initial rise
then fall

28. BisoDIAS
Endgültig
28
Bisoprolol: Long-term treatment of hypertension
140
SBP(mm Hg)
100
DBP(mm Hg)
HR(beats/min)
60
0
n = 102
12
15
18
21
24
27
30
33
36 months
102
97
102
101
102
102
102
100
102
Giesecke HG et al. J Cardiovasc Pharmacol 1990; 16 (Suppl 5): 175
180

29. This is how braunwald’s textbook
summarizes the use of betablockers in
hypertension
 “Beta blockers are specifically recommended for
hypertensive patients with concomitant coronary
disease, particularly after a myocardial infarction,
congestive heart failure, or tachyarrhythmias.”
 “If a beta blocker is chosen, the agents that are more
cardioselective offer the likelihood of fewer
perturbations of lipid and carbohydrate metabolism
and, because of fewer side effects (except for
bradycardia), better adherence to therapy.”
 “Long-acting formulations are better for once-daily
dosing.”
Page 945 braunwald’s
textbook of medicine 9th edition

30. From: Cardiovascular Protection Using Beta-Blockers: A Critical Review of the Evidence
J Am Coll Cardiol. 2007;50(7):563-572. doi:10.1016/j.jacc.2007.04.060
Figure Legend:
Proposed Use of Beta-Blockers for Hypertension
In patients with uncomplicated hypertension, beta-blockers should not be used as
first-line agents. However, in patients with uncontrolled hypertension on various
other antihypertensive agents and in those with complicated hypertension, betablockers should be considered in the armamentarium of treatment. CHF = chronic
heart failure; MI = myocardial infarction. College of Cardiology.
Copyright © The American
All rights reserved.

31. Bisoprolol experience in
Indian patients
Mar
2012

32. Bisoprolol in hypertension
Objectives:
This study was aimed to evaluate the
efficacy and tolerability of
bisoprolol, in Indian patients
diagnosed with stage I essential
hypertension as first line drug.
Primary and secondary outcomes measures:
The primary outcome measure was
percentage of patients achieving
blood pressure (BP) <140/90 mm Hg
at the end of 12 weeks, while
Channaraya V, Marya RK, Somasundaram M, et al. BMJ Open 2012;2:e000683
multiple secondary outcome


33. RESULT
2131 (96.44%) patients n: 2418
achieved BP control.

34. Different beta blockers and sexual
dysfunction versus placebo

35. Conclusion:
Cardioselective beta-blockers
(Bisoprolol) is important part of CVD
management

36. THANK YOU!