Beta Blocker Therapy in

Chronic Heart Failure from

Contraindication
to Indication
Based on CIBIS Study
Pembimbing : Prof. dr. WH Sibuea, Sp.PD

GAGAL JANTUNG

NYHA
Classification

-blocking Effects

 Blockers Mechanisms
in CHF
Bradycardia
Protection from catecholamin
myocyte toxicity
Improved 1 adrenergic
signaling
Antiapoptosis
Renin angiotensin inhibition

Excess Adrenergic Signals in CHF

CIBIS and CIBIS II

(Cardiac Insufficiency Bisoprolol
Study)
Controlled clinical studies in which

bisoprolol
was
compared
with
placebo, which included 3288 (641 &
2647) patients with CHF.
The main outcomes were total death,
cardiovascular death, sudden death,
hospitalization for heart failure, and
myocardial infarction

METHODS
Both studies were double-blind, placebo

controlled trials with an initial dose of 1.25

mg of bisoprolol
Patients were to have symptomatic chronic
heart failure (NYHA scale III or IV) from any
etiology, present for at least 3 months
before randomization with a documented
impaired ejection fraction (EF) of <40% in
CIBIS and <35% in CIBIS II
In both studies treatments were titrated to
the maximal tolerated dose, up to a
maximal dose of 5 mg of bisoprolol in CIBIS

CIBIS III Trial

1010 patients > 65 years with mild to moderate CHF (NYHA class
II or III) and LV ejection fraction < 35% in 3 months prior to
randomization, clinically stable CHF for 7 days
Randomized
32% female, mean age 72 years, mean follow-up 1.22 years
13% received aldosterone-receptor blocker and 84% diuretic

Monotherapy with ACEMonotherapy with betainhibitor enalapril (first 6

blocker bisoprolol (first 6
mos)
mos)
10mg B.I.D.
10mg O.D.
n=505
n=505
Combination beta-blocker and
ACE-inhibitor therapy (6-24
mos)

Primary Endpoint: Time-to-the-first-event of combined all-cause mortality

and all-cause hospitalization throughout study.
Secondary Endpoint: Combined primary endpoint at end of monotherapy
phase; individual components of primary endpoint at study end and at
end of monotherapy phase.

Presented
Presented at
at ESC
ESC 2005
2005

Recommended Procedure
for Starting Blockers
On

ACEi, if no contraindicated
In a relatively stable condition
Start with a very low dose, go slow
Titrate up to maintenance dosages
shown to be effective
The dose may be doubled in every
1-2 weeks if preceding dose was
well tolerated

Thank You
In youth we learn
In age we understand
Mary Von Ebner Eschenbach