Prospective Randomized Amlodipine Survival Evaluation-1 - PRAISE-1

May 15, 2002
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Date Published:
01/01/1996
Date Updated:
05/15/2002
Original Posted Date:
05/15/2002
References

Description:

Amlodipine for morbidity and mortality in advanced heart failure.

Hypothesis:

Contrasted with treatment using other calcium-channel blockers that may worsen heart failure and increase the risk of death in patients with left ventricular dysfunction, the long-term use of amlodipine may reduce symptoms and increase survival in patients with advanced chronic heart failure.

Study Design

Study Design:

Patients Screened: Not given
Patients Enrolled: 1,153
NYHA Class: class III = 471 patients in the placebo group (41%) and 460 patients in t
Mean Follow Up: 6 to 33 months with a median of 13.8 months
Mean Patient Age: 64.7
Female: 24
Mean Ejection Fraction: 0.21 ±0.01

Patient Populations:

Dyspnea or fatigue at rest or on minimal exertion (NYHA class IIIB or IV).
Left ventricular ejection fraction <30% despite treatment with digoxin, diuretics, and an angiotensin-converting-enzyme (ACE) inhibitor.

Exclusions:

"Non-nitrate vasodilator drugs (e.g., hydralazine), but treatment with nitrates was allowed
Uncorrected primary valvular disease
Active myocarditis
Constrictive pericarditis
History of cardiac arrest
Sustained ventricular tachycardia or fibrillation within the previous year
Unstable angina
Acute myocardial infarction within the previous month
Cardiac revascularization procedure or stroke within the previous three months
Severe pulmonary, renal, or hepatic disease
Systolic blood pressure <85 mmHg or >159 mmHg
Diastolic blood pressure >89 mmHg
Serum creatinine concentration >3.0 mg/dL (270 µmol/L)
Potassium concentration <3.5 or >5.5 mmol/L
Treatment with beta-blockers, calcium-channel blockers, or class IC antiarrhythmic agents
No intravenous (IV) diuretics or vasodilators within 24 hours before enrollment
No IV positive inotropic agents within 72 hours before enrollment
Signed informed consent"

Primary Endpoints:

Combined risk of mortality from all causes and cardiovascular morbidity (hospitalization for major cardiovascular events).

Secondary Endpoints:

Mortality from all causes

Drug/Procedures Used:

Initial dose of 5 mg of amlodipine or placebo once daily for two weeks; dose then increased (if tolerated) to 10 mg of amlodipine or placebo once daily for the remainder of the study.

Concomitant Medications:

Nitrates

Principal Findings:

Primary end points were reached in 42% of the placebo group and 39% of the amlodipine group, representing a 9% reduction in the combined risk of fatal and nonfatal events with amlodipine (95% confidence interval, 24% reduction to 10% increase; P = 0.31).

A total of 38% in the placebo group died, as compared with 33% of those in the amlodipine group, representing a 16% reduction in the risk of death with amlodipine (95% confidence interval, 31% reduction to 2% increase; P = 0.07).

Among patients with ischemic heart disease, there was no difference between the amlodipine and placebo groups in the occurrence of either endpoint. In contrast, among patients with nonischemic cardiomyopathy, amlodipine reduced the combined risk of fatal and nonfatal events by 31% (P = 0.04) and decreased the risk of death by 46% (P <0.001).

Interpretation:

Amlodipine did not increase cardiovascular morbidity or mortality in patients with severe heart failure. The possibility that amlodipine prolongs survival in patients with nonischemic dilated cardiomyopathy requires further study. A second amlodipine trial (PRAISE-2) is being conducted to study treatment of patients with nonischemic dilated cardiomyopathy.

References:

1. N Engl J Med 1996;335:1107-14. Final results

Keywords: Myocardial Ischemia, Digoxin, Diuretics, Heart Failure, Stroke Volume, Amlodipine, Confidence Intervals, Dyspnea, Ventricular Dysfunction, Left, Calcium Channel Blockers, Cardiomyopathy, Dilated


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