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The Effects of Oral Milrinone on Mortality in Severe Chronic Heart failure - PROMISE
Description:
Milrinone for mortality in symptomatic advanced heart failure.
Hypothesis:
Milrinone improves mortality in patients with advanced heart failure who remain symptomatic despite conventional therapy.
Study Design
Study Design:
- Randomized
Patients Enrolled: 200
Mean Follow Up: 30 days
Mean Patient Age: Mean age 62 years
Female: 17
Patient Populations:
Patients with ejection fraction < 35% and NYHA class III-IV heart failure on digoxin, diuretics, ACE inhibitor for at least 3 months. Symptoms at rest within 2 weeks.
Exclusions:
Obstructive valvular disease, myocarditis, restrictive cardiomyopathy or hypertrophic cardiomyopathy.
History of serious symptomatic ventricular arrhythmia
Angina or recent myocardial infraction
Severe pulmonary hypertension
Systemic blood pressure < 85 mm Hg
Hypokalemia
Treatment with beta blockers, calcium channel blockers or antiarrhythmic agents
Primary Endpoints:
All cause mortality
Secondary Endpoints:
Cardiovascular mortality
Number of hospitalizations
Addition of vasodilators for worsening heart failure
Symptoms
Adverse reactions
Drug/Procedures Used:
Milrinone 40 mg/day (could be increased or decreased throughout study)
Concomitant Medications:
Digoxin (100%)
Diuretics (100%)
ACE inhibitor (100%)
Nitrates (59%)
Antiarrhythmics (26%)
Principal Findings:
168 deaths (30%) in milrinone group and 127 (24%) in placebo; 28% increase in all cause mortality (p = 0.038) and 34% in cardiovascular mortality (p = 0.016).
Adverse effect of milrinone noted in all subgroups; milrinone increased mortality significantly in subgroups with low serum sodium, increased cardiothoracic ratio, and NYHA functional class IV.
No beneficial effect of milrinone on symptoms or functional capacity.
Mortality with milrinone was greatest in class IV patients (53%).
Serum magnesium does not appear to be an independent risk factor for either sudden death or death due to all causes in patients with moderate to severe heart failure.
Interpretation:
Oral milrinone increases mortality and morbidity in patients with severe heart failure who remain symptomatic despite conventional therapy with digoxin, diuretics, ACE inhibitor. The study was stopped prematurely on October 4, 1990, five months before scheduled completion due to the increased mortality in the treatment group.
References:
1. N Engl J Med 1991;325:1468-75. Final results
2. J Am Coll Cardiol 1993;21:634-40. Magnesium substudy
Keywords: Magnesium, Milrinone, Diet, Sodium-Restricted, Sodium, Digoxin, Diuretics, Heart Failure, Risk Factors, Death, Sudden, Cardiac
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