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CLINICAL STUDIES

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

Stuart D. Katz, MD^*, Michael Radin, MD, FACC, Thomas Graves, PhD, Cynthia Hauck, MS, Alan Block, PhD, Thierry H. LeJemtel, MD for the Ifetroban Study Group

^* Columbia Presbyterian Medical Center, Division of Circulatory Physiology, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York, USA
Pacific Coast Cardiology, Newport Beach, California, USA
Bristol Myers Squibb, Princeton, New Jersey, USA
Albert Einstein College of Medicine, Division of Cardiology, Department of Medicine, New York, New York, USA

Manuscript received October 13, 1998; revised manuscript received February 17, 1999, accepted March 24, 1999.

Reprint requests and correspondence: Dr. Stuart D. Katz, Columbia Presbyterian Medical Center, Division of Circulatory Physiology, Room MHB5-435, 177 Fort Washington Avenue, New York, New York 10032
sdk8{at}columbia.edu

OBJECTIVES

The purpose of this study was to determine the acute and chronic effects of cyclooxygenase inhibition with aspirin and thromboxane A₂ receptor blockade with ifetroban on the chronic vasodilating effects of enalapril in the skeletal muscle circulation of patients with heart failure.

BACKGROUND

Angiotensin-converting enzyme inhibition and antiplatelet therapy with aspirin independently reduce the risk for subsequent nonfatal coronary 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 of vasodilating prostaglandins.

METHODS

Forearm blood flow (ml/min/100 ml) at rest and during rhythmic handgrip exercise and after transient arterial occlusion was determined by strain gauge plethysmography before and 4 h and six weeks after combined administration of enalapril with either aspirin, ifetroban or placebo in a multicenter, double-blind, randomized trial of 62 patients with mild to moderate heart failure.

RESULTS

Before randomization, forearm hemodynamics were similar in the three treatment groups except for increased resting forearm blood flow and decreased resting forearm vascular resistance in the aspirin group when compared with the placebo group. After combined administration of enalapril and study drug for 4 h and six weeks, changes from prerandomization values of mean arterial pressure, forearm blood flow and forearm vascular resistance at rest, during handgrip exercise and after transient arterial occlusion did not differ among the three treatment groups.

CONCLUSIONS

These findings demonstrate that the vasodilating effects of enalapril in the skeletal muscle circulation of patients with heart failure are not critically dependent on prostaglandin pathways.

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