Author + information
- Received January 2, 2013
- Revision received April 4, 2013
- Accepted April 11, 2013
- Published online August 1, 2013.
- Milton Packer, MD∗ (, )
- Peter Carson, MD,
- Uri Elkayam, MD,
- Marvin A. Konstam, MD,
- Gordon Moe, MD,
- Christopher O'Connor, MD,
- Jean-Lucien Rouleau, MD,
- Douglas Schocken, MD,
- Susan A. Anderson, MS,
- David L. DeMets, PhD,
- PRAISE-2 Study Group∗
- ↵∗Reprint requests and correspondence:
Dr. Milton Packer, Department of Clinical Sciences, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390.
Objectives This study was designed to test the hypothesis of whether amlodipine reduces the risk for death in patients with heart failure due to a nonischemic cardiomyopathy.
Background A pre-specified subgroup analysis in an earlier, large-scale, placebo-controlled study suggested that amlodipine might reduce the risk for death in patients with heart failure due to a nonischemic cardiomyopathy.
Methods To evaluate this hypothesis, 1654 patients with severe heart failure due to a nonischemic cardiomyopathy (ejection fraction <30%) were randomly assigned to amlodipine (target dose: 10 mg/d) or placebo added to conventional therapy for heart failure for a median of 33 months.
Results There were 278 deaths in the amlodipine group and 262 deaths in the placebo group (hazard ratio: 1.09; 95% confidence interval [CI]: 0.92 to 1.29; p = 0.33). The differences between the 2 groups in the risks for cardiovascular death and hospitalization were also not significant. When the results from patients with a nonischemic cardiomyopathy in both the earlier trial and in the current study were combined, there was no evidence of a favorable or unfavorable effect of amlodipine on mortality (hazard ratio: 0.97; 95% CI: 0.83 to 1.13; p = 0.66). Both trials, however, observed higher frequencies of peripheral edema and pulmonary edema and lower frequencies of uncontrolled hypertension and chest pain in patients treated with amlodipine.
Conclusions These results of the current trial, viewed together with the results from the earlier study, indicate that amlodipine does not exert favorable effects on the clinical course of patients with heart failure, regardless of the presence or absence of underlying coronary artery disease. These findings indicate the need for great caution when striking benefits are observed in subgroups of patients or in trials not primarily designed to assess such effects.
This research was supported by a grant from Pfizer, Inc. Dr. Packer has received consultant's fees from Actelion, Amgen, BioControl, Janssen, Johnson & Johnson, Cardiorentis, CardioKinetix, CardioMEMS, Novartis, Onyx, Pfizer, Piramal, Polyphor, and Sanofi. Dr. Konstam has received research support and/or consultant's fees from Amgen, Johnson & Johnson, Merck, Otsuka, and Pfizer, Inc. Dr. Rouleau has received consultant's fees from Novartis. Dr. Schocken has received speaker's honoraria from Otsuka America Pharmaceutical. Dr. DeMets has served on data-monitoring committees and has received honoraria for several industry-sponsored trials. The authors have reported that they have no other relationships relevant to the contents of this paper to disclose. Paul Armstrong, MD, acted as Guest Editor for this paper.
- Received January 2, 2013.
- Revision received April 4, 2013.
- Accepted April 11, 2013.
- 2013 American College of Cardiology Foundation