A comparative analysis of the results from 4 trials of beta-blocker therapy for heart failure: BEST, CIBIS-II, MERIT-HF, and COPERNICUS.
BACKGROUND
Recent large randomized, controlled trials (BEST [Beta-blocker Evaluation of Survival Trial], CIBIS-II [Cardiac Insufficiency Bisoprolol Trial II], COPERNICUS [Carvedilol Prospective Randomized Cumulative Survival Study], and MERIT-HF [Metoprolol Randomized Intervention Trial in Congestive Heart Failure]) have addressed the usefulness of beta-blockade in the treatment of advanced heart failure. CIBIS-II, COPERNICUS, and MERIT-HF have shown that beta-blocker treatment with bisoprolol, carvedilol, and metoprolol XL, respectively, reduce mortality in advanced heart failure patients, whereas BEST found a statistically nonsignificant trend toward reduced mortality with bucindolol. We conducted a post hoc analysis to determine whether the response to beta-blockade in BEST could be related to differences in the clinical and demographic characteristics of the study populations. We generated a sample from BEST to resemble the patient cohorts studied in CIBIS-II and MERIT-HF to find out whether the response to beta-blocker therapy was similar to that reported in the other trials. These findings are further compared with COPERNICUS, which entered patients with more severe heart failure.


METHODS
To achieve conformity with the entry criteria for CIBIS-II and MERIT-HF, the BEST study population was adjusted to exclude patients with systolic blood pressure <100 mm Hg, heart rate <60 bpm, and age >80 years (exclusion criteria employed in those trials). The BEST comparison subgroup (BCG) was further modified to more closely reflect the racial demographics reported for patients enrolled in CIBIS-II and MERIT-HF. The association of beta-blocker therapy with overall survival and survival free of cardiac death, sudden cardiac death, and progressive pump failure in the BCG was assessed.


RESULTS
In the BCG subgroup, bucindolol treatment was associated with significantly lower risk of death from all causes (hazard ratio (HR)=0.77 [95% CI=0.65, 0.92]), cardiovascular death (HR=0.71 [0.58, 0.86]), sudden death (HR=0.77 [0.59, 0.999]), and pump failure death (HR=0.64 [0.45, 0.91]).


CONCLUSIONS
Although not excluding the possibility of differences resulting from chance alone or to different properties among beta-blockers, this study suggests the possibility that different heart failure population subgroups may have different responses to beta-blocker therapy.
Clinical Trials Group, National Heart, Lung, and Blood Institute/NIH, 6701 Rockledge Drive, Room 8146, Bethesda, MD 20892-7936, USA.
Michael J
MJ
Domanski
Heidi
H
Krause-Steinrauf
Barry M
BM
Massie
Prakash
P
Deedwania
Dean
D
Follmann
David
D
Kovar
David
D
Murray
Ron
R
Oren
Yves
Y
Rosenberg
James
J
Young
Michael
M
Zile
Eric
E
Eichhorn
D000293:Adolescent; D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002423:Cause of Death; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000401:mortality*; D006801:Humans; D008297:Male; D015201:Meta-Analysis as Topic; D008875:Middle Aged; D012107:Research Design; D015996:Survival Rate
D000319:Adrenergic beta-Antagonists