Clopidogrel treatment reduces platelet activity in vivo, but does not counteract exercise-induced platelet activation

Abstract number: P0243

Perneby C., Hu H., Li N., Daleskog M., Johansson M.-C., Wallén N. H., Hjemdahl P.

Karolinska Hospital, Sweden

Platelet activation by stress and physical exertion may contribute to the triggering of acute coronary syndromes. ADP is involved in shear induced platelet activation in vitro, and may contribute to stress-induced platelet activation. Thus ADP receptor antagonism by clopidogrel treatment might attenuate exercise induced platelet activation in vivo. We studied 15 healthy male volunteers who performed exhaustive exercise with and without pretreatment with clopidogrel (75 mg day^-1; 7 days) in a randomized cross-over study. Filtragometry readings (reflecting platelet aggregability) and 11-dehydro-thromboxane B₂ (TXM) levels in plasma were determined before and after exercise. Platelet P-selectin expression without and with ADP and thrombin stimulation in vitro, and circulating platelet-platelet aggregates (PPA) were determined by whole-blood flow cytometry. Clopidogrel treatment inhibited ADP (10⁵ M) induced P-selectin expression by 72 ± 10% (SD). Workloads (264 ± 53 W without treatment), and increases in heart rate (from 68 ± 11 to 188 ± 28 bpm) and systolic blood pressure (from 115 ± 10 to 178 ± 29 mmHg) during exercise were similar on the two occasions. Exercise evoked platelet activation, as shown by (untreated data): shortened filtragometry readings (-51 ± 17%; P < 0.01), increased single platelet P-selectin expression and elevated circulating PPAs, enhanced ADP and thrombin stimulated P-selectin expression (P < 0.001 for both), and elevated TXM in plasma (0.64 ± 0.24–0.91 ± 0.44 pg mL^-1; P < 0.01). At rest, clopidogrel treatment reduced platelet aggregability (prolonged filtragometry readings), and attenuated both ADP and thrombin stimulated P-selectin expression, without influencing TXM in plasma or urine. Clopidogrel treatment did not significantly attenuate any of the platelet responses to exercise, as evaluated by two factor repeated measures anova:s. We conclude that clopidogrel treatment attenuates platelet activity in vivo at rest, but that exercise counteracts the platelet stabilizing effects of clopidogrel. The hypothesis that ADP receptor stimulation contributes to the platelet activating effect of stress is not supported.