Minoxidil in patients with chronic left heart failure: contrasting hemodynamic and clinical effects in a controlled trial.
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 (11.7 +/- 6.3[SD] vs 17.1 +/- 3.1 U at baseline; p less than .05). Hemodynamics were similar at baseline and remained unchanged during placebo treatment. Mean left ventricular ejection fraction rose from 29.6 +/- 17.7% to 42.7 +/- 22.3% (p less than .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 less than .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.
D000368:Aged; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D002986:Clinical Trials as Topic; D004077:Digoxin / Q000627:therapeutic use; D004232:Diuretics / Q000627:therapeutic use; D004311:Double-Blind Method; D006333:Heart Failure / Q000188:drug therapy*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D008875:Middle Aged; D008914:Minoxidil / Q000627:therapeutic use*; D005082:Physical Exertion; D011743:Pyrimidines / Q000627:therapeutic use*; D011897:Random Allocation; D013318:Stroke Volume / Q000187:drug effects; D013997:Time Factors; D014655:Vascular Resistance / Q000187:drug effects
D004232:Diuretics; D011743:Pyrimidines; D008914:Minoxidil; D004077:Digoxin