ATLANTA, Nov. 10 - A study sponsored by the National Heart, Lung, and Blood Institute (NHLBI) and the Department of Veterans Affairs (VA) found that the beta-blocker bucindolol did not reduce death from heart failure. This finding contrasts with results from other trials of beta-blockers.
The reasons for the unexpected results of the Beta-Blocker Evaluation of Survival Trial (BEST) are not yet clear. However, they may be due to BEST's use of a different beta-blocker and to its greater number of African Americans and persons with severe heart failure.
Results of BEST were presented here today during the 72nd Scientific Sessions of the American Heart Association in Atlanta, Ga.
The study, which began enrollment in 1995, examined whether bucindolol, a beta-blocker drug, improved survival in patients with moderate to severe heart failure. The drug works by blocking the action of catecholamines, chemicals released by the body when the heart's pumping ability weakens. At first, catecholamines make the heart pump harder, but over time cause a progressive decrease in heart function.
BEST was conducted at 90 clinical sites in the United States and Canada. The study enrolled 2,708 participants. About 33 percent of the participants were U.S. veterans; 22 percent were women; and 30 percent were from minority groups. The average age of the participants was 60 years. BEST is the first heart failure study to include substantial numbers of African Americans and patients with advanced heart failure.
Patients were randomized to receive either the beta-blocker bucindolol or a placebo. All patients also received standard heart failure therapy. Thus, almost all patients (more than 90 percent) were on an angiotensin converting enzyme (ACE) inhibitor, a diuretic, and digitalis. Ninety-two percent of the BEST participants had moderately severe heart failure (Class III) at the time of their enrollment in the study, and 8 percent had severe heart failure (Class IV). The average left ventricular ejection fraction (a key indicator of how well the heart pumps) was 23 percent. The most common cause of the heart failure was coronary artery disease.
The study, which had been scheduled to end in June 2000, was stopped in July 1999 at the recommendation of its Data and Safety Monitoring Board (DSMB). The DSMB based its recommendation upon the totality of evidence available in BEST, as well as on recent findings from other studies, specifically the Cardiac Insufficiency Bisoprolol Study II (CIBIS II) and the Metroprolol CR/XL Randomized Intervention Trial in Heart Failure (MERIT-HF).
Researchers are still examining the reasons for the difference in overall results between BEST and those studies. One factor may be the type of beta-blocker used: BEST patients were treated with bucindolol, while those in studies finding improved survival used metoprolol and bisoprolol. Another possible factor is that BEST participants had more advanced heart failure than those in other studies.
"BEST found somewhat different results for various subgroups of participants," said Dr. Michael Domanski, Leader of NHLBI's Clinical Trials Scientific Research Group. "Those with moderate heart failure and those not African American appeared to gain a benefit from the drug, but African Americans and those with the most severe heart failure did not."
The differences by subgroup and between the results of BEST and other large trials raises the possibility that some heart failure patients may not derive a benefit from, or could even be harmed by, the use of beta-blockers, Domanski said.
"The results of this trial compared to other trials of less advanced heart failure also highlight the need for earlier intervention with beta-blockers in many patients with weak hearts," said Study Co-Chairman Dr. Eric Eichhorn, Professor of Medicine at the University of Texas Southwestern and Dallas VA Medical Centers.
BEST results underscore the need for further research to determine which patients are most likely to benefit from beta-blocker therapy, Domanski and Eichhorn emphasized, as well as the need to examine gender, racial, and ethnic differences in future studies of cardiovascular disease.
To arrange an interview with Domanski, contact the NHLBI Communications Office at (301) 496-4236. For an interview with Eichhorn, contact the VA Office of Public Affairs at (212) 807-3429.