Prospective Randomized Amlodipine Survival Evaluation 2 - PRAISE-2

Description:

The goal of the trial was to evaluate treatment with amlodipine compared with placebo among patients with nonischemic cardiomyopathy.

Hypothesis:

Amlodipine, when added to standard therapy, will improve survival in moderate to severe heart failure due to nonischemic cardiomyopathy.

Study Design

  • Randomized
  • Blinded

Patients Screened: Not given
Patients Enrolled: 1,654
NYHA Class: IIIB/IV
Mean Follow Up: 33 months
Mean Patient Age: 59 years
Female: 34%
Mean Ejection Fraction: 21%

Patient Populations:

  • NYHA functional class III/IV and treatment with ACE inhibitor, digitalis, and diuretic for at least 3 months
  • Left ventricular ejection fraction <29%
  • Nonischemic heart failure
  • Six-minute walk with distance covered <375 m

Exclusions:

  • Angina or coronary artery disease
  • History of aborted sudden cardiac death
  • Sustained ventricular tachycardia not effectively treated/controlled with medication or implantable cardioverter-defibrillator
  • Amlodipine
  • Beta-blockers
  • Calcium channel blockers

Primary Endpoints:

  • All-cause mortality

Secondary Endpoints:

  • Cardiovascular mortality
  • Health care resource utilization

Drug/Procedures Used:

Patients with New York Heart Association (NYHA) functional class III or IV due to nonischemic cardiomyopathy were randomized to amlodipine 10 mg/day (n = 827) versus matching placebo (n = 827).

Concomitant Medications:

Digitalis, diuretics, and angiotensin-converting enzyme (ACE) inhibitor

Principal Findings:

Overall 1,654 patients were randomized. The mean age was 59 years, 66% were men, mean left ventricular ejection fraction was 21%, and mean systolic blood pressure was 120 mm Hg.

The primary outcome, all-cause mortality at a median follow-up of 33 months, was 33.6% in the amlodipine group and 31.7% in the placebo group (p = 0.32) by intention to treat. Analysis of data from patients in the first and second PRAISE trials was combined, and all-cause mortality was 31.1% among those who received amlodipine and 32.0% among those who received placebo (p = 0.6).

Interpretation:

The results of PRAISE-2 did not validate the favorable association of amlodipine with improved survival for patients with nonischemic heart failure observed in the initial PRAISE-1 trial. Combined analysis of both trials suggests that amlodipine has no appreciable harmful or beneficial effect on mortality in patients with severe chronic heart failure. The unexpected findings of the larger randomized PRAISE-2 trial, illustrate the pitfalls of drawing conclusions from benefits that are small in absolute magnitude and are obtained from subgroup analyses.

References:

Parker M, Carson P, Elkayam U, et al. Effect of Amlodipine on the Survival of Patients With Severe Chronic Heart Failure Due to a Nonischemic Cardiomyopathy: Results of the PRAISE-2 Study (Prospective Randomized Amlodipine Survival Evaluation 2). JACC Heart Fail 2013;1:308-14.

Packer M. Results from late-breaking clinical trials sessions at ACCIS 2000 and ACC 2000. J Am Coll Cardiol 2000;36:255-61.

Clinical Topics: Heart Failure and Cardiomyopathies, Acute Heart Failure

Keywords: Follow-Up Studies, Cardiomyopathies, Diuretics, Heart Failure, Digitalis Glycosides, Stroke Volume, Blood Pressure, Amlodipine, Systole, Calcium Channel Blockers


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