PRO-HEMORRHAGIC EFFECTS OF CALCIUM-ANTAGONISTS - A COMPARISON OF ISRADIPINE AND ATENOLOL ON EX-VIVO PLATELET-FUNCTION IN HYPERTENSIVE SUBJECTS

It has been suggested that long term treatment with calcium antagonist drugs might inhibit platelet function and lead to an anti-atheromatou s effect. However recent data have also suggested that such an effect might increase mortality due to an increased incidence of gastrointest inal bleeding. We identified 43 subjects from general practice with un complicated mild to moderate hypertension to compare the effects of th e calcium antagonist isradipine with that of the beta-blocker atenolol on platelet function, plasma beta-thromboglobulin levels, fibrinolysi s, and serum lipids in a randomised double-blind parallel group study. After careful evaluation to exclude concomitant aspirin use, only 24 subjects were eligible to enter the study. While isradipine and atenol ol produced comparable and clinically significant falls in blood press ure (167 +/- 2/102 +/- 1 to 153 +/- 3/91 +/- 2 mm Hg, and 165 +/- 2/10 1 +/- 1 to 156 +/- 4/91 +/- 2 mm Hg, respectively), neither drug produ ced a detectable effect on ex vivo platelet aggregation, platelet rete ntion, or thromboxane generation with adrenaline, collagen, adenosine- di-phosphate, or platelet activating factor. However a decrease in pla sma beta-thromboglobulin levels was observed which reached statistical significance (P < 0.05) after 12 weeks treatment in the isradipine bu t not the atenolol group. A 39% reduction with isradipine compared wit h 34% following atenolol treatment. Euglobulin clot lysis time was not altered by either drug. Serum cholesterol concentrations were also un altered by drug treatment. Therapeutic doses of the calcium antagonist isradipine may produce a minor indirect effect on platelet function a fter several weeks of treatment. However, this is of doubtful clinical importance and may simply reflect an effect of lowered blood pressure on platelet function.