Association Between Residual Platelet Reactivity on Clopidogrel Treatment and Severity of Coronary Atherosclerosis: Intrinsic Hypercoagulability as a Mediator.

INTRODUCTION: High on-treatment residual platelet reactivity (HRPR) was associated with greater atherosclerosis burden. We examined whether intrinsic hypercoagulability (IHC) could be attributed to that association in patients treated by drug-eluting stents.

METHODS: This retrospective observation enrolled a total of 891 coronary artery disease (CAD) subjects. Platelet and coagulant reactivity was measured by thrombelastography. At least 24 h after a 300-mg dose of clopidogrel, adenosine diphosphate (ADP)-induced maximum amplitude of clot strength (MAadp ) > 47 mm represented HRPR. Thrombin-induced platelet-fibrin clot strength (MAthrombin ) and blood fibrinogen surrogated intrinsic coagulability. Using mediation analysis to evaluate the effect of IHC on the relationship between the number of narrowed coronaries and HRPR on clopidogrel.

RESULTS: More HRPR on clopidogrel and higher intrinsic coagulability were observed in more severe coronary atherosclerosis, especially in the three-vessel disease. After adjustment for confounding factors, the number of narrowed coronaries (ORadj  = 1.343, 95% CI 1.063-1.695, p = 0.013), MAthrombin (ORadj  = 1.106, 95% CI 1.058-1.157, p < 0.001), and fibrinogen (ORadj  = 1.003, 95% CI 1.001-1.005, p = 0.012) were all independent positive predictors for HRPR. MAthrombin and fibrinogen were meaningful mediators for the significant positive association of the number of narrowed vessels and HRPR on clopidogrel, which were enhanced by around 30% and 43%, respectively, for this effect.

CONCLUSIONS: This is the first study to demonstrate that the positive correlation between the number of stenotic coronaries and HRPR on clopidogrel may be partly attributed to IHC, which may enhance the risk stratification, guide more precise coagulation in multi-vessel disease after drug-eluting stents, and therefore deserve further study.