Embargoed for Release: May 30, 2001, 5:00 PM EDT
Embargoed for Release: May 30, 2001, 5:00 PM EDT
A study sponsored by the National Heart, Lung, and Blood Institute (NHLBI) and the Department of Veterans Affairs (VA) found that, overall, the beta-blocker bucindolol did not increase survival for moderate to severe heart failure.
The results also showed racial differences in the drug's effects, although the reasons for these differences are not yet clear. Black heart failure patients received no benefit from bucindolol, while non-black patients treated with the drug lived longer. Non-black patients included whites, Hispanics, Asian/Pacific Islanders, and American Indian/Alaskan Natives. There were no differences by gender in the drug's effects.
The findings of the Beta-Blocker Evaluation of Survival Trial (BEST), which contrast with those of other beta-blocker studies, appear in the May 31 issue of the New England Journal of Medicine.
Other results from BEST are consistent with findings from earlier beta-blocker studies and include: fewer deaths from cardiovascular disease, fewer and shorter hospitalizations for heart failure, and fewer deaths or heart transplants for those treated with bucindolol, compared to the placebo.
"The results from BEST offer physicians valuable added guidance about the use of beta-blockers for heart failure," said NHLBI Director Dr. Claude Lenfant. "Its results also underscore the need to examine gender, racial, and ethnic differences in future studies of cardiovascular disease."
"Based on the large amount of evidence of benefit of beta-blockers from previous studies, beta-blockers should be considered for all heart failure patients at this time, including African American patients. However, further research is needed in this population," said BEST Co-Chair Dr. Eric Eichhorn of the Dallas VA Medical Center.
"In BEST, there was a trend toward longer survival for study participants treated with bucindolol who had less advanced heart failure," said Dr. Michael Domanski, Leader of NHLBI's Clinical Trials Scientific Research Group. "That and the results of earlier studies show how important it is to treat heart failure early, when beta-blockers can make a real difference in survival."
BEST was the first beta-blocker heart failure study to include substantial numbers of black patients and patients with advanced heart failure. It began enrollment in 1995 and was conducted at 90 clinical sites in the United States and Canada. The study enrolled 2,708 participants - about 33 percent were U.S. veterans; about 22 percent were women; and about 30 percent were from minority groups. The average age of participants was 60 years.
Participants were randomized to receive either bucindolol or a placebo. All patients also received standard heart failure therapy. More than 90 percent of patients were treated with an angiotensin converting enzyme (ACE) inhibitor, a diuretic, and digitalis.
At the time of enrollment, 92 percent of participants had moderately severe heart failure (Class III) 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 participants' heart failure was coronary artery disease.
BEST had been scheduled to end in June 2000, but 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 and the Metoprolol CR/XL Randomized Intervention Trial in Heart Failure.
Follow-up of BEST participants lasted an average of 2 years. Ultimately, 449 (33 percent) of the placebo group and 411 (30 percent) of the bucindolol group died.
"Sometimes you learn more from a neutral trial than a positive one," said Eichhorn, "and this is one of those cases where we learned a tremendous amount. We know that, all in all, other beta-blockers are good for heart failure patients and probably African American heart failure patients as well."
"It's still unclear why bucindolol had such varied effects among these patients," said Domanski. "Other trials had found an overall survival benefit, but they differed from BEST in some key ways. They used different beta blockers, had a less diverse population, with fewer black participants, had a shorter follow-up period, and were done outside the United States, where patient care may have been managed differently. More research is needed so we can understand which patients will benefit from which beta blocker."
To arrange an interview with an NHLBI scientist, 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.