Effects of treatment with oral isosorbide dinitrate on platelet function in vivo; a double-blind placebo-controlled study in patients with stable angina pectoris.
1. A randomised double-blind placebo-controlled cross-over study was performed to investigate the effects of oral isosorbide dinitrate (ISDN; 20 mg twice daily for 2 weeks) on various aspects of platelet function in vivo in 20 patients with stable angina pectoris. Measurements were performed at rest and after platelet activation by physical exercise (bicycle ergometry). 2. Compared with placebo, treatment with ISDN significantly decreased systolic blood pressure at rest by 7 (-14 to -1) mm Hg (mean and 95% CI) and tended to increase exercise capacity by 7 (-1 to 14) W and attenuate perceived chest pain during maximal work. The dosage was high, as judged by side-effects reported (mainly headache). Compliance was good, as assessed by electronic counter equipped tablet bottles (Medication Event Monitoring System); only one patient had a compliance rate below 60%. 3. Exercise significantly increased platelet aggregability as measured by filtragometry ex vivo; the time taken for platelet aggregates in whole blood drawn directly from an antecubital vein to occlude a microfilter was significantly decreased from 155 to 95 s (antilog of mean log values). Platelet secretion in vivo also increased, as indicated by significant elevations of beta-thromboglobulin in plasma; from 22 to 35 ng ml-1 (P = 0.006). 4. ISDN treatment did not inhibit platelet function. Relative to placebo, filtragometry readings (ISDN/placebo ratios; mean and 95% CI) were not altered either at rest (1.05 (0.83 to 1.32)) or immediately after exercise (0.98 (0.80 to 1.20)). Similarly, beta TG in plasma was unaltered by ISDN treatment; 1.09 (0.98 to 1.21) at rest, and 1.04 (0.82 to 1.30) immediately after exercise.(ABSTRACT TRUNCATED AT 250 WORDS)
Wallén
N H
NH
Department of Clinical Pharmacology, Karolinska Hospital, Stockholm, Sweden.
Andersson
A
A
Hjemdahl
P
P
D000284:Administration, Oral; D000368:Aged; D000787:Angina Pectoris / Q000097:blood*; D001792:Blood Platelets / Q000187:drug effects*; D003404:Creatinine / Q000652:urine; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005080:Exercise Test; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007548:Isosorbide Dinitrate / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D010349:Patient Compliance; D010974:Platelet Aggregation / Q000187:drug effects; D013929:Thromboxane B2 / Q000031:analogs & derivatives / Q000378:metabolism; D001620:beta-Thromboglobulin / Q000378:metabolism
D001620:beta-Thromboglobulin; D013929:Thromboxane B2; C049235:11-dehydro-thromboxane B2; D003404:Creatinine; D007548:Isosorbide Dinitrate