Gender and Responses to Aspirin and Clopidogrel: Insights Using Short Thrombelastography

Abstract

There is significant variability in both baseline clotting tendency and response to antiplatelet therapy. Responses are associated with outcome. We have investigated whether differences could explain the increased risk observed in women presenting with coronary artery disease. We have utilized short thrombelastography to assess (i) baseline clotting responses, (ii) response to aspirin and clopidogrel, and (iii) post-treatment platelet reactivity in 48 young volunteers, 22 older patients and 18 patients with previous stent thrombosis. Baseline responses were significantly higher in young women than in men. While there was no difference in response to aspirin, platelet reactivity on aspirin remained higher in women (area under curve at 15 min [AUC15] of arachidonic acid channel 332 ± 122 vs. 172 ± 80, P = 0.04). Young women had less response to clopidogrel (% reduction in AUC15 with adenosine diphosphate [ADP] 36.4 ± 12.4 vs. 64.0 ± 13.2, P < 0.01) in addition to higher post-treatment reactivity (AUC15 of ADP 714 ± 161 vs. 311 ± 146, P < 0.01) compared to men. There were no such differences between male and female patients over 50. However, young women with previous stent thrombosis had among the highest platelet reactivity observed. Compared to men, young women have greater baseline clotting tendency, reduced response to clopidogrel, and greater post-treatment reactivity while on both aspirin and clopidogrel. Differences in clotting tendency and response to antiplatelet therapy may contribute to the excess risk observed in young women but are not observed in older female patients.

Relationship between thromboelastography and long-term ischemic events as gauged by the response to clopidogrel in patients undergoing elective percutaneous coronary intervention

“…Interestingly, the current results based on a Cox model indicated that female patients had a much higher risk of experiencing ischemic events than did male patients, and a previous study yielded a similar finding. Several studies have indicated that HPR is more prevalent in females than males because of a stronger platelet aggregation reaction to platelet agonist stimulation (13)(14)(15). This might be caused by a high of clotting at the baseline, the effects of female hormone, or a diminished reaction to clopidogrel in female patients.…”

Bedside stratification of patients according to CYP2C19*2 genotype

“…Hobson and his colleagues demonstrated that there were both an elevated baseline clotting tendency and a reduced response to clopidogrel in young healthy females as compared to that in males. No such differences among males and females were observed in an older or postmenopausal female (Hobson et al, 2009). By contrast, males had a higher risk of developing CAD as compared with females, with the highest relative risk in young adults.…”

Population pharmacodynamics of cilostazol in healthy Korean subjects

“…This result was consistent with previous reports; caffeine inhibited platelet aggregation by up-regulating adenosine A 2A receptor, [19] and chronic coffee drinking decreased platelet aggregation. [20] For the influence of sex, previous studies in Caucasians reported that baseline platelet aggregation in females was higher than that in males, [21][22][23] whereas in a study conducted in a healthy Korean population CTs were reported to be significantly longer in females. [17] Although one possible reason for this inconsistency would be a race difference (Caucasian versus Asian), more studies will be needed to better understand the influence of sex on CT.…”