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Curriculum Vitae

• Name : Prof. DR. Dr. Idrus Alwi SpPD, K-KV, FACC, FESC,
FAPSIC, FINASIM, FACP.
• Current Position : President of Indonesian Society of
Internal Medicine

• Medical Student : Faculty of Medicine University of Indonesia 1986


• Internist : Faculty of Medicine University of Indonesia 1996
• Cardiovascular Consultant : The Indonesian Society of Internal Medicine , 2001
• PhD : Faculty of Medicine University of Indonesia, 2006
• FACC : American College of Cardiology, 2006
• FESC : European Society of Cardiology, 2008
• FAPSIC : Asia Pacific Society of Interventional Cardiology, 2009
• FINASIM : Indonesian Society of Internal Medicine, 2009
• FACP : American Colleague of Physician, 2013
• Advanced Course in Cardiology, Melbourne 1997
• Advanced Course on Echocardiography and Others Non Invasive Cardiology,
Melbourne 1997.
• Stem cell NOGA course, Cincinnatti, Ohio, 2009
• ASAN Interventional Cardiology Course, Seoul, 2011
Position of Selective and Non ISA Beta Blocker in
Hypertension with or without Compelling
Indication

Prof. Idrus Alwi MD, PhD, FINASIM, FACC, FESC, FAPSIC, FACP

Division of Cardiology, Department of Internal Medicine,


Faculty of Medicine , University of Indonesia,
Jakarta , Indonesia
Hypertension With Compelling

Indications
ESH/ESC: Antihypertensive Treatment Preferred Drug

- ACE Aldo-
Diuretic ARB CCB
blocker inhibitor antagonist

Heart failure
• • • • •
Post-MI
• • •
Angina
pectoris • •
Diabetes
• •
Renal
dysfunction • •
Previous
stroke
Any blood pressure lowering agent

Mancia G, Fagard R, et al. J Hypertens 2013, 31:1281–1357


Early Administration of Beta-Blockers Did Not Improve
the In-Hospital Mortality of Patients Admitted with
Acute Coronary Syndrome

Beta-Blocker No Beta-Blocker

Events Total Events Total 95% CI

2355 36173 2465 36076 0.90,1.01

Favors beta- Favors


blockers controls
Brandler E, et al. Acad Emerg Med 2010;17:1-10
Beta blockers without intrinsic
sympathomimetic activity should be used,
especially beta-1 blockers such as
sustained-release metoprolol succinate,
bisoprolol, or carvedilol, a beta-1 and
alpha-1 blocker. This is because of their
mortality benefit in patients with HF and
systolic dysfunction

Amsterdam EA, et al. J Am Coll Cardiol.) (2014), doi: 10.1016/j.jacc.2014.09.017.


Βeta blockade after myocardial infarction:
systematic review of 54 234 patients

Short term Long term


Odds of Death (%)

Freemantle N, et al. BMJ 1999;318:1730-7


Beta-Blocker Use and Clinical Outcomes in Stable Outpatients

Known CAD without Prior MI Known Prior MI


Event rate for primary outcome, %

HR, 0.92 (95% CI, 0.79-1.08); HR, 0.90 (95% CI, 0.79-1.03);
P = .31 P = .14

No β-blocker β-blocker
No β-blocker
β-blocker

Follow-up, mo
Follow-up, mo

Bangalore S, et al. JAMA. 2012;308:1340-1349


Class IA beta-blockers

1. Bisoprolol

2. Metoprolol succinate ACC/AHA1


ESC2
3. Carvedilol

4. Nebivolol

1. Yancy CW, et al. Circulation. 2013;128:e240-e327


2. McMurray JJV, et al. Eur Heart J 2012);33:1787–1847
Event Rate Reduction
Hospital
All-cause admission
All-cause hospital All CV Sudden for heart
mortality admission mortality death failure
0
Event rate reduction (%)

-10

-20
-20
p=0.0006
-30
-29
p=0.0049
-40 -36
p=0.0001
-44 -44
-50 p<0.0001 p=0.0011

The CIBIS-II Investigators and Committees. Lancet 1999;353:9-13


Relationship of Beta-Blocker Dose With Outcomes in
Ambulatory Heart Failure Patients With Systolic
Dysfunction

Fiuzat M, et al. Am Coll Cardiol 2012;60:208–15


DOSE TITRATION
6 mo’s 24 mo’s

0 2 4 6 8 10 12 28 30 32 32 32

20
82% of 65% of
10
patients patients 5
10
enalapril (mg/d)
7.5
5
3.75
2.5
1,25 bisoprolol (mg/d)

10
7.5
5
3.75
2.5
1,25
20 bisoprolol (mg/d)
10
5
enalapril (mg/d)
Overall tolerability to target doses was comparable. The

pattern of intolerance, however, was different:

bradycardia occurred more often in the bisoprolol group,

whereas pulmonary adverse events occurred more often

in the carvedilol group.


ADHERE Registry 2006-2009
Chronic Outpatient Medication Prior to Hospitalization

APLA AP LA
n=10,878 n=10,166 n=712
ACEi or ARB (%) 49.2 48.3 62.2
ACE Inhibitor (%) 36.3 35.5 47.8
Angiotensin II Receptor Blocker (%) 15.0 14.9 16.2
Aldosterone Receptor Antagonist (%) 21.5 20.6 34.1

Aspirin (ASA) (%) 41.1 41.5 35.1


Beta Blocker (%) 37.4 36.5 50.9
Digoxin (%) 26.6 26.1 33.8
Diuretic (%) 57.7 57.0 68.7

Lipid Lowering (%) 38.6 39.6 24.7


Nitrate (%) 30.9 32.1 13.5
Subcutaneous Erythropoietin (%) 1.4 1.5 0.3
Warfarin (%) 13.9 13.7 17.4
Hypertension Without

Compelling Indications
The current Guidelines reconfirm that diuretics (including
thiazides, chlorthalidone and indapamide), beta-blockers,
calcium antagonists, angiotensin converting enzyme
(ACE) inhibitors and angiotensin receptor blockers are all
suitable for the initiation and maintenance of
antihypertensive treatment, either as monotherapy or in
some combinations.
Mancia G, et al. J Hypertens 2013;31:1281–1357
JAMA. doi:10.1001/jama.2013.284427

β-blockers are not recommended for the initial

treatment of hypertension because the evidence was

insufficient to make a determination


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

Smooth muscle: blood vessels 1 Vasodilatation (coronary)

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


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


Risk Ratio of Beta-blockers Compared to Diuretics,
Calcium Channel Blockers, and RAS Inhibitors on
Stroke, Cardiovascular Disease, and Total Mortality

Risk ratio (95% CI)

Beta-blockers vs.
Cardiovascular
Stroke Total mortality
disease

Diuretics 0.92 [0.55, 1.54] 1.13 [0.99, 1.28] 1.04 [0.91, 1.19]

Calcium channel
1.24 [1.11, 1.40] 1.18 [1.08, 1.29] 1.07 [1.00, 1.14]
blockers

RAS inhibitors 1.30 [1.11, 1.53] 1.00 [0.72, 1.38] 1.10 [0.98, 1.24]

Wiysonge CS, et al. Cochrane Database Syst Rev 2012, Nov 14,11:CD002003.doi
Antihypertensive class effect on peripheral SBP minus central SBP

Antihypertensive ΔpSBP – ΔcSBP


95% CI
agent (mm Hg)
ACE-I -2.40 −4.89 to 0.08
ARB 1.12 −2.25 to 4.49
BB 5.19 3.21-7.18
CCB 1.01 −2.17 to 4.19
Diuretic 0.65 −2.47 to 3.77
ACE-I + ARB 1.00 −17.19 to 19.19
ACE-I + Diuretic 0.29 −3.74 to 4.32
ARB + CCB 2.81 −3.31 to 8.94
ARB + Diuretic 4.28 −3.27 to 11.82
BB + CCB 2.10 −2.21 to 6.41
BB + Diuretic 10.80 −3.47 to 24.67
CCB + Diuretic 6.00 −0.08 to 12.08
McGaughey TJ, et al. Am J Hypertens 2015. doi:10.1093/ajh/hpv134
Differential Impact of Blood Pressure–Lowering Drugs on
Central Aortic Pressure and Clinical Outcomes: Principal Results
of the Conduit Artery Function Evaluation (CAFE) Study

Williams B, et al. Circulation 2006;113;1213-1225


Effects of bisoprolol and atenolol on brachial BP
and central aortic pressure

Zhou WJ, et al. PLoS ONE 8(9): e72102. doi:10.1371/journal.pone.0072102


TAKE-HOME MESSAGES
 Bisoprolol is among all beta-blockers that
should be used for secondary prevention after
MI.

 Bisoprolol is among few beta-blockers that


should be used for improving survival of
patients with chronic heart failure.

 Compared with atenolol, bisoprolol may have


less dysmetabolic effects and better effect on
central aortic pressure.
Thank You
For Your Kind Attention