Congestive Heart Failure
Effect of amlodipine on mode of death among patients with advanced heart failure in the praise trial

https://doi.org/10.1016/S0002-9149(98)00496-2Get rights and content

Abstract

Investigations of calcium antagonists in patients with advanced heart failure have raised concern over an increased risk of worsening heart failure and heart failure deaths. We assessed the effect of amlodipine on cause-specific mortality in such patients enrolled in a randomized, double-blind, placebo-controlled trial. In total, 1,153 patients in New York Heart Association class IIIb or IV heart failure were randomized to receive amlodipine or placebo, along with angiotensin-converting enzyme inhibitors, diuretics, and digitalis. Over a median 14.5 months of follow-up, 413 patients died. Cardiovascular deaths accounted for 89% of fatalities, 50% of which were sudden deaths and 45% of which were due to pump failure, with fewer attributed to myocardial infarction (3.3%) or other cardiovascular causes (1.6%). Amlodipine treatment resulted in a greater relative reduction in sudden deaths (21%) than in pump failure deaths (6.6%) overall. When patients were classified by etiology of heart failure (ischemic or nonischemic), cause-specific mortality did not differ significantly between treatment groups in the ischemic stratum. In the nonischemic stratum, however, sudden deaths and pump failure deaths were reduced by 38% and 45%, respectively, with amlodipine. Thus, when added to digitalis, diuretics, and angiotensin-converting enzyme inhibitors in patients with advanced heart failure, amlodipine appears to have no effect on cause-specific mortality in ischemic cardiomyopathy, but both pump failure and sudden deaths appear to be decreased in nonischemic heart failure patients treated with amlodipine.

Section snippets

Patient population

The PRAISE trial was a randomized, double-blind, placebo-controlled study of amlodipine versus placebo treatment of 1,153 patients with severe chronic heart failure despite treatment with angiotensin-converting enzyme inhibitors, digitalis, and diuretics. The details of the study design and patient population have been described previously.6

End points

The primary end point of the PRAISE trial was the combined incidence of death (categorized as cardiovascular or noncardiovascular) or severe cardiovascular

Patient population

The PRAISE trial was conducted over a 34-month period ending December 31, 1994. At the time of termination, 1,153 patients had been enrolled. Of the 732 patients enrolled with ischemic heart disease, 370 were assigned to treatment with placebo and 362 to treatment with amlodipine. Of the 421 patients enrolled with nonischemic dilated cardiomyopathy, 212 were assigned to treatment with placebo and 209 to treatment with amlodipine. The 2 treatment groups were similar with respect to baseline

Discussion

When added to digitalis, diuretics, and angiotensin-converting enzyme inhibitors, amlodipine resulted in a 16% reduction in the hazard of mortality in the 1,153 patients with advanced heart failure enrolled in the PRAISE trial,6 with a 6% reduction in pump failure deaths and a 21% reduction in sudden cardiac deaths. Whereas the relative reduction in overall mortality was modest, the absolute benefit was more striking because of the high event rates in congestive heart failure.

The overall

Acknowledgements

We would like to thank Milton Packer, MD, Robert Califf, MD, Wendy Gattis, PharmD, and Alan Kraska, PhD, for critically reviewing the manuscript. We also thank the PRAISE trial team: Lynn Vesey, Karen Soileau, Jean Glaze, Helene Minor, LeeAnn Robinson, Kathy Miller, Laura Sears, Dorothy Gardiner, Samantha Wolfe, and Dave Rendall. Finally, our thanks to Pat Williams for editorial support and Crystal Crawford, Sue Ann Gentry, and Renee Story for manuscript preparation.

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    This work was supported by Pfizer, Groton, Connecticut. Manuscript received February 24, 1998; revised manuscript received and accepted May 15, 1998.

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