Oral verapamil inhibits platelet thrombus formation in humans.
BACKGROUND
Calcium antagonists such as verapamil are potent coronary and systemic vasodilators that are used in the treatment of coronary disease. They have also been shown to inhibit platelet aggregation in vitro, but whether they have beneficial antithrombotic effects in humans is unclear, and whether they can potentiate the antithrombotic effects of aspirin is unknown.


RESULTS
Platelet thrombus formation and whole blood platelet aggregation were measured in 18 stable coronary patients on three separate occasions: at baseline when receiving no active medications, after 7 days of receiving oral verapamil SR (240 mg/d), and after 7 days of receiving a combination of oral verapamil SR and aspirin (325 mg/d). Thrombus formation on porcine aortic media that were placed into cylindrical flow chambers and exposed to flowing antecubital venous blood for 3 minutes was assessed morphometrically 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 microns 2, and this was decreased to 3.1 +/- 0.5 microns 2 (P < .05) after 7 days of treatment with oral verapamil SR and to 2.6 +/- 0.5 microns 2 (P < .05) after 7 days of treatment with oral verapamil and aspirin. Whole 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; aggregation 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 treatment with verapamil and aspirin to 6.1 +/- 1.1 and 7.2 +/- 1.0 omega (P < .05), respectively.


CONCLUSIONS
The present study demonstrates that part of the benefit of verapamil in ischemic heart disease may occur by inhibition of platelet aggregation and thrombus formation. This beneficial antithrombotic effect may be important in preventing acute coronary ischemic events resulting from thrombus formation at sites of plaque rupture.
L-Lacoste
L
L
Department of Medicine, Montreal Heart Institute, Quebec, Canada.
Lam
J Y
JY
Hung
J
J
Waters
D
D
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000787:Angina Pectoris / Q000150:complications / Q000188:drug therapy; D001241:Aspirin / Q000627:therapeutic use; D001792:Blood Platelets / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects; D003692:Delayed-Action Preparations; D004338:Drug Combinations; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects; D013927:Thrombosis / Q000517:prevention & control*; D014700:Verapamil / Q000008:administration & dosage* / Q000627:therapeutic use
D003692:Delayed-Action Preparations; D004338:Drug Combinations; D014700:Verapamil; D001241:Aspirin