The Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS) study determined that at a mean follow-up of 10.4 months, carvedilol, a beta-adrenergic blocker, reduced death by 35 percent when compared with placebo. Krum and colleagues address concerns that initiation of beta-blocker therapy in patients with heart failure may precipitate hypotension or worsening heart failure in the first four to eight weeks of therapy.
The COPERNICUS study randomized patients with severe heart failure to receive carvedilol, starting with a 3.125-mg dosage twice daily and titrating upward to a target dosage of 25 mg twice daily, or placebo. All patients were treated with a diuretic and an angiotensin-converting enzyme inhibitor or angiotensin-II receptor antagonist.
Of the 2,289 patients enrolled in the study, 1,133 were assigned to the placebo group and 1,156 to the carvedilol group. During the first eight weeks, fewer patients in the carvedilol group died, were hospitalized, or permanently withdrew from carvedilol therapy than those in the placebo group. Similar findings were observed when analysis was applied solely to the highest-risk patients. Benefits began to appear as early as two to three weeks after initiation of carvedilol therapy.
The authors conclude that clinically euvolemic patients had no increased adverse effects from initiation and up-titration of carvedilol therapy. There were infrequent adverse side effects, such as dizziness and bradycardia. The study also demonstrates the nearly immediate benefits of beta-adrenergic blockade.