ORAL VERAPAMIL INHIBITS PLATELET THROMBUS FORMATION IN HUMANS

Background Calcium antagonists such as verapamil are potent coronary a nd systemic vasodilators that are used in the treatment of coronary di sease. They have also been shown to inhibit platelet aggregation in vi tro, but whether they have beneficial antithrombotic effects in humans is unclear, and whether they can potentiate the antithrombotic effect s of aspirin is unknown. Methods and Results Platelet thrombus formati on and whole blood platelet aggregation were measured in 18 stable cor onary patients on three separate occasions: at baseline when receiving no active medications, after 7 days of receiving oral verapamil SR (2 40 mg/d), and after 7 days of receiving a combination of oral verapami l SR and aspirin (325 mg/d). Thrombus formation on porcine aortic medi a that were placed into cylindrical flow chambers and exposed to flowi ng antecubital venous blood for 3 minutes was assessed morphometricall y at a shear rate of 2546 s(-1), which is typical of arterial flow at sites of stenoses. Thrombus formation under basal conditions was 7.0+/ -1.6 mu m(2), and this was decreased to 3.1+/-0.5 mu m(2) (P<.05) afte r 7 days of treatment with oral verapamil SR and to 2.6+/-0.5 mu m(2) (P<.05) after 7 days of treatment with oral verapamil and aspirin. Who le blood platelet aggregation levels in response to 0.050 and 0.075 U of thrombin at baseline were 10.8+/-1.0 and 11.9+/-1.0 Omega; aggregat ion was inhibited after 7 days of treatment with verapamil to 6.5+/-1. 1 and 7.8+/-0.9 Omega (P<.05 versus baseline) and after 7 days of trea tment with verapamil and aspirin to 6.1+/-1.1 and 7.2+/-1.0 Omega (P<. 05), respectively. Conclusions The present study demonstrates that par t of the benefit of verapamil in ischemic heart disease may occur by i nhibition of platelet aggregation and thrombus formation. This benefic ial antithrombotic effect may be important in preventing acute coronar y ischemic events resulting from thrombus formation at sites of plaque rupture.