Combination of fosinopril and pravastatin decreases platelet response to thrombin receptor agonist in monkeys.

Published

Journal Article

Both angiotensin-converting enzyme (ACE) inhibitors and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors have been shown to decrease cardiovascular morbidity and mortality. Results from clinical trials have suggested that HMG-CoA reductase inhibition might exert a beneficial effect independent of its lipid-lowering effect, and ACE inhibition may exert a benefit independent of blood-pressure lowering. To test the hypothesis that such an effect might be mediated by alteration in platelet reactivity, we studied 55 monkeys receiving both, 1, or neither of the ACE inhibitor fosinopril and the HMG-CoA reductase inhibitor pravastatin. Platelet responsiveness to collagen and to the thrombin receptor agonist (TRA) SFLRRN-NH2 was determined by aggregometry. For each agonist, the maximum rate and extent of aggregation were measured for each dose, and the concentration required for half-maximal response (C50) was determined. Each drug, when given alone, slightly decreased the dose of agonist required to produce 50% response in the rate and extent of platelet aggregation relative to control. The combination of the 2 drugs, however, produced a significant increase in the dose of TRA required to produce 50% response in the rate and extent of aggregation relative to either drug alone or the control group. This was not true for collagen. The magnitude of the change relative to the control group, 47% for rate and 30% for extent of aggregation, could confer considerable protection by changing the threshold for thrombin-induced platelet aggregation and, thus, decrease thrombosis.

Full Text

Cited Authors

  • Hale, LP; Craver, KT; Berrier, AM; Sheffield, MV; Case, LD; Owen, J

Published Date

  • October 1998

Published In

Volume / Issue

  • 18 / 10

Start / End Page

  • 1643 - 1646

PubMed ID

  • 9763538

Pubmed Central ID

  • 9763538

Electronic International Standard Serial Number (EISSN)

  • 1524-4636

International Standard Serial Number (ISSN)

  • 1079-5642

Digital Object Identifier (DOI)

  • 10.1161/01.atv.18.10.1643

Language

  • eng