Effect of aspirin and ifetroban on skeletal muscle blood flow in patients with congestive heart failure treated with enalapril

OBJECTIVES The purpose of this study was to determine the acute and chronic effects of cyclooxygenase inhibition with aspirin and thromboxane A(2) rec eptor blockade with ifetroban on the chronic vasodilating effects of enalap ril in the skeletal muscle circulation of patients with heart failure. BACKGROUND Angiotensin-converting enzyme inhibition and antiplatelet therap y with aspirin independently reduce the risk for subsequent nonfatal corona ry events in survivors of myocardial infarction. The safety of the combined administration of angiotensin-converting enzyme inhibitors and aspirin has been questioned due to their divergent effects on the vascular synthesis o f vasodilating prostaglandins. METHODS Forearm blood flow (ml/min/100 mi) at rest and during rhythmic hand grip exercise and after transient arterial occlusion was determined by stra in gauge plethysmography before and 4 ii and six weeks after combined admin istration of enalapril with either aspirin, ifetroban or placebo in a multi center, double-blind, randomized trial of 62 patients with mild to moderate heart failure. RESULTS Before randomization, forearm hemodynamics were similar in the thre e treatment groups except for increased resting forearm blood flow and decr eased resting forearm vascular resistance in the aspirin group when compare d with the placebo group. After combined administration of enalapril and st udy drug for 4 h and six weeks, changes from prerandomization values of mea n arterial pressure, forearm blood flow and forearm vascular resistance at rest, during handgrip exercise and after transient arterial occlusion did n ot differ among the three treatment groups. CONCLUSIONS These findings demonstrate that the vasodilating effects of ena lapril in the skeletal muscle circulation of patients with heart failure ar e not critically dependent on prostaglandin pathways. (C) 1999 by the Ameri can College of Cardiology.