Impact of Anemia on Platelet Reactivity and Ischemic and Bleeding Risk: From the Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents Study.

Anemic patients remain at increased risk of ischemic and bleeding events. Whether the effects of hemoglobin levels on thrombotic and bleeding risk are independent of platelet reactivity on clopidogrel, however, remains unknown. Patients from the Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents study were categorized by the presence of anemia at baseline, defined according the World Health Organization criteria. Platelet reactivity was measured with VerifyNow assay; high platelet reactivity (HPR) on clopidogrel was defined as platelet reactive units value >208. Of 8,413 patients included in the study cohort, 1,816 (21.6%) had anemia. HPR was more prevalent in patients with anemia (58.3% vs 38.4%; p <0.001), an association that persisted after multivariate adjustment (adjusted odds ratio: 2.04; 95% confidence interval [CI]: 1.82 to 2.29; p <0.0001). Patients with anemia had higher 2-year rates of major adverse cardiac events (9.5% vs 5.6%; p <0.0001), major bleeding (11.8% vs 7.7%; p <0.0001), and all-cause mortality (4.0% vs 1.4%; p <0.0001); however, after adjustment for baseline clinical confounders, including HPR, anemia was no longer significantly associated with major adverse cardiac events but was still independently associated with all-cause mortality (adjusted HR 1.61, 95% CI 1.23 to 2.12; p <0.0001) and major bleeding (adjusted HR 1.42, 95% CI 1.20 to 1.68; p <0.0001). The effect of HPR on clinical outcomes was uniform according to anemia status, without evidence of interaction. In conclusion, anemia independently correlated with HPR. After percutaneous coronary intervention with drug-eluting stents, anemia at baseline was significantly associated with higher 2-year hemorrhagic and mortality risk; conversely, its association with ischemic risk was attenuated after multivariate adjustment, including HPR.

Relation Between Platelet Count and Platelet Reactivity to Thrombotic and Bleeding Risk: From the Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents Study.

Whether the association between platelet count (PC) and thrombotic and bleeding risk is independent of or varies by residual platelet reactivity to antiplatelet therapies is unclear. We sought to investigate the independent and combined effects of PC and platelet reactivity on thrombotic and bleeding risk after coronary artery implantation of drug-eluting stents (DES). Patients enrolled in the prospective, multicenter Assessment of Dual AntiPlatelet Therapy with Drug-Eluting Stents study were stratified by PC tertiles. The study cohort comprised 8,402 patients. By linear regression analysis, lower PC was strongly and independently associated with higher platelet reactive units (PRUs) on clopidogrel. After multivariable adjustment (including PRU and aspirin reactive units), high, but not low, PC tertile was independently associated with higher risk of thrombotic complications, including spontaneous myocardial infarction and stent thrombosis. Although no independent association was observed between PC tertiles and hemorrhagic risk, both high and low PC tertiles were associated with increased risk for all-cause mortality. After stratification of PC tertiles by tertiles of PRUs, the crude risk of thrombotic complications was highest in patients in the high PC and high PRU tertiles. By multivariable adjustment, PRU increases were uniformly associated with higher risk of thrombotic events across PC tertiles, without evidence of interaction. In conclusion, higher PCs and higher PRUs act independently and synergistically in determining thrombotic risk. Alongside PRU, PCs could be a simple hematological parameter to consider for risk stratification and in tailoring duration and potency of pharmacologic platelet inhibition after DES implantation.