Therapy and Prevention Congestive Heart Failure

Minoxidil, a potent predominant arterial dilator, improves hemodynamics over the short term in patients with heart failure. In random double-blind fashion 17 patients with chronic left heart failure were given minoxidil (nine patients) or placebo (eight patients) in addition to digoxin and diuretics for 3 months. Cardiac index and heart rate increased and mean arterial pressure and systemic vascular resistance fell within 4 hr of minoxidil administration. Right heart and pulmonary arterial pressures were unchanged over the short term but rose after long-term minoxidil. After 3 months of minoxidil treatment, systemic vascular resistance was still reduced (1 1.7 6.3 [SD] vs 17. 1 3 1 U at baseline; p < .05). Hemodynamics were similar at baseline and remnained unchanged during placebo treatment. Mean left ventricular ejection fraction rose from 29.6 + 17.7% to 42.7 + 22.3% (p < .05) after 3 months of minoxidil treatment (this result was influenced largely by responses in two patients), and remained unchanged (at 25.1 ± 16.6%) after 3 months of placebo. Exercise duration and maximal oxygen uptake during exercise were unchanged during minoxidil or placebo treatment. Total clinical events, including increased need for diuretics, angina, ventricular arrhythmias, worsening heart failure, and death were all more frequent during minoxidil vs placebo administration (21 vs seven total events; p < .01). Thus, despite improving hemodynamics and left ventricular function, long-term minoxidil administration was associated with a poorer clinical course in patients with chronic left ventricular failure. Furthermore, this experience demonstrates that improvement of left ventricular function alone cannot be reliably interpreted as proof of clinical efficacy of therapeutic interventions in patients with heart failure. Circulation 70, No. 1, 63-68, 1984. MINOXIDIL is a potent, orally effective, direct-acting arterial dilator that improves left ventricular performance over the short term in patients with congestive heart failure.1 Long-term beneficial effects of minoxidil have been reported in uncontrolled trials in heart failure, but the effects of hydralazine, a similar drug, were no different than those of placebo in controlled studies." This study was designed to assess the effects of long-term minoxidil administration in patients with chronic left ventricular failure in a controlled trial. The From the Cardiovascular Division, Veterans Administration Medical Center and University of Pennsylvania, Philadelphia; and the Cardiovascular Division, Veterans Administration Medical Center and University of Arkansas for Medical Sciences, Little Rock. Supported in part by grants from the Medical Research Service of the Veterans Administration, Washington, D.C., and from the Upjohn Company, Kalamazoo, MI. Address for correspondence: Joseph A. Franciosa, M.D., Cardiovascular Division, University of Arkansas for Medical Sciences, 4301 West Markham, Mail Slot 532, Little Rock, AR 72205. Received Nov. 8, 1983; revision accepted Feb. 28, 1984. Presented in part at the Annual Meeting, American College of Cardiology, New Orleans, March 1983. Vol. 70, No. 1, July 1984 study was undertaken despite the well-known sympathetic stimulation and fluid retention produced by minoxidil in hypertensive patients because other vasodilators that have similar effects in hypertensive patients have not usually produced these effects in patients with heart failure.t