Effect of aspirin and ifetroban on skeletal muscle blood flow in patients with congestive heart failure treated with Enalapril. Ifetroban Study Group.
OBJECTIVE
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.
Columbia Presbyterian Medical Center, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA. sdk8@columbia.edu
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SD
Katz
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Radin
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T
Graves
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Hauck
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Block
T H
TH
LeJemtel
D000368:Aged; D001241:Aspirin / Q000494:pharmacology*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004311:Double-Blind Method; D004347:Drug Interactions; D004656:Enalapril / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D005542:Forearm / Q000098:blood supply; D006333:Heart Failure / Q000188:drug therapy / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000098:blood supply*; D010080:Oxazoles / Q000494:pharmacology*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D010991:Plethysmography; D012039:Regional Blood Flow / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology / Q000627:therapeutic use*
D019086:Bridged Bicyclo Compounds, Heterocyclic; D016861:Cyclooxygenase Inhibitors; D010080:Oxazoles; D010975:Platelet Aggregation Inhibitors; D014665:Vasodilator Agents; D004656:Enalapril; C078904:ifetroban; D001241:Aspirin