The CIBIS III trial compared bisoprolol first and enalapril first regimens.
CIBIS Investigators and Committees, A randomized trial of beta-blockade in heart failure.
In CIBIS II, 15% of the patients randomized to bisoprolol stopped taking it; (1) in COPERNICUS, the withdrawal rate from carvedilol was also 15%; (2) and in MERIT-HE 10% of patients taking metoprolol experienced an adverse event that led to drug withdrawal.
TABLE 1 Beta-blockers for heart failure patients: What the studies show Mean Agent Trial Study group (N) follow-up tested BESTS Class III-IV HF EF 2 y Bucindolol [less than or equal to] 535% (2708) CIBIS II (1) Class III-IV HF EF 1.
This is precisely the purpose of the CIBIS
III trial, which aims to answer the question of whether initiation of CHF therapy with a beta-blocker is comparable (non-inferior) to the initiation of therapy with an ACE inhibitor.
However, the results are not inconsistent with those of other studies, specifically MERIT-HF and CIBIS
TABLE Selected trials of beta-blockers for systolic dysfunction Mortality reduction 95% Study Drug N (%) CI (%) US Carvedilol (1) Carvedilol 1094 (65) 39-80 COPERNICUS (2) Carvedilol 2289 (35) 19-48 MERIT-HF (3) Metoprolol 3991 (34) 19-46 CIBIS
II (4) Bisoprolol 2647 (34) 19-47 BEST (5) Bucindolol 2708 (9) -0.
FIGURE EFFECT OF B-BLOCKER THERAPY ON TOTAL MORTALITY [ILLUSTRATION OMITTED] Clinical Trial [Beta]-Blocker Placebo (Number of deaths/ number at risk) CIBIS
 53/320 67/321 CIBIS
-II 156/1327 228/1320 ANZ 20/208 26/207 US Carvedilol 22/696 31/398 MDC 23/194 19/189 MERIT-HF 145/1990 217/2001 Overall -- -- CIBIS
denotes Cardiac Insufficiency Bisoprolol Study; CIBIS
-II, Cardiac Insufficiency Bisoprolol Study II; ANZ, Australia/New Zealand Heart Failure Research Collaborative Trial; US Carvedilol, US Carvedilol Heart Failure Program; MDC, Metoprolol in Dilated Cardiomyopathy trial; MERIT-HF, Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart