Drug sequence not crucial in heart failure treatment.
Treatment of heart failure typically begins with an ACE inhibitor or an angiotensin-receptor blocker, mainly for historic reasons: ACE inhibitors were proven effective for treating heart failure first. But results from a head-to-head trial now show that both options are equivalent. An ACE inhibitor or a [beta]-blocker can be started first, followed by the other drug, with similar outcomes, Ronnie Willenheimer, M.D., said at the annual congress of the European Society of Cardiology.
"This will possibly change practice. The data support using a [beta]-blocker first in selected patients," commented Kenneth Dickstein, M.D., a cardiologist at the University of Bergen (Norway).
"It remains a clinical question [as to] who should get a [beta]-blocker first and who should first get an ACE inhibitor or angiotensin-receptor blocker," Dr. Dickstein added.
"The results suggest free choice. A physician can start treatment based on individual judgment of each patient," Dr. Willenheimer, a cardiologist at University Hospital Malmo (Sweden), told this newspaper. "For patients with tachycardia or ischemic cardiomyopathy, I'd start with a [beta]-blocker."
Dr. Willenheimer has received honoraria from the German division of Merck, which sponsored the study and markets a formulation of the [beta]-blocker bisoprolol (Concor) approved in many countries (but not the United States) for treating heart failure. In the United States, generic bisoprolol and its trade formulation (Zebeta) are approved only for treating hypertension; [beta]-blockers approved for treating heart failure are carvedilol (Coreg) and metoprolol succinate (Toprol-XL).
The study enrolled 1,010 patients aged 65 years or older with New York Heart Association class II or III heart failure at 128 centers in 20 countries. The mean left ventricular ejection fraction was 29%. Patients were randomized to start with 1.25 mg of bisoprolol once daily or 2.5 mg of the ACE inhibitor enalapril b.i.d. The monotherapy dosage was increased every 2 weeks until the bisoprolol dosage was 10 mg once daily or the enalapril dosage was 10 mg b.i.d. After 6 months, the second drug was begun with similar uptitration. Patients were followed for a mean of 1.2 years.
By all efficacy measures, the bisoprolol-first strategy was not inferior to the enalapril-first regimen. The primary end point was the time to first all-cause death or all-cause hospitalization. During follow-up on an intention-to-treat basis, these events occurred in 35.2% of patients in the bisoprolol-first arm and 36.8% of those in the enalapril-first arm. On a per-protocol basis, the event rates were 32.4% (bisoprolol first) and 33.1% (enalapril first). The results were also published in Circulation (http://circ.ahajournals.org/cgi/reprint/CIRCULATIONAHA.105.582320v1).
The incidence of treatment-related adverse events was similar in both groups. In patients treated with bisoprolol first, there was a trend toward improved survival and a trend toward a higher frequency of worsening heart failure requiring hospitalization, especially early in the study.
These findings are probably class effects, Dr. Willenheimer said. In both treatment groups, the drug that was started first was given in higher dosages during the combined therapy phase.
Dr. Dickstein noted that the study was done on an open-label basis and did not include patients with class IV disease. Also, patients remained on monotherapy for the relatively long period of 6 months.
BY MITCHEL L. ZOLER
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|Author:||Zoler, Mitchel L.|
|Publication:||Internal Medicine News|
|Date:||Nov 1, 2005|
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