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

https://doi.org/10.1016/j.amjcard.2016.03.001Get rights and content

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.

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Methods

ADAPT-DES was a prospective, nonrandomized, international, multicenter study designed to determine the incidence, timing, and predictors of ST after DES implantation.4 The major exclusion criteria were the occurrence of a serious adverse event during PCI or before platelet reactivity testing and planned bypass surgery after PCI. All patients received aspirin and clopidogrel before PCI. Platelet function tests were performed after successful PCI the day after the procedure by means of the

Results

Overall, 8,402 patients were included in the study cohort. Of them, 2,763 (32.9%), 2,828 (33.7%), and 2,811 patients (33.5%) were distributed across the lowest, intermediate, and highest PC tertile, respectively. PC interquartile range in the lowest tertile was 152 to 183, in the intermediate was 205 to 231, and in the highest was 261 to 315 (per 103/mm3​). Baseline clinical characteristics are described in Table 1. Patients in the low tertile were older, more commonly men, of Caucasian

Discussion

The present analysis, drawn from more than 8,000 patients undergoing successful DES implantation, is to the best of our knowledge the largest study evaluating the relation between PC and PRU and their independent and combined effect on thrombotic, hemorrhagic, and mortality outcomes in an all-comers PCI population. The main findings of the present analysis include: (1) lower levels of PC were strongly and independently associated with higher residual platelet reactivity on clopidogrel; (2) high

Disclosures

Dr. Généreux receives Speaker's fee from Abbott Vascular and Edwards Lifescience; consulting fees from Cardiovascular Systems Inc.; and institutional research grant from Boston Scientific. Drs. Mehran and Dangas receives research grant support from Eli Lilly, AstraZeneca, The Medicines Company, BMS/Sanofi-Aventis; consulting fees from AstraZeneca, Bayer, CSL Behring, Janssen Pharmaceuticals, Merck, Osprey Medical Inc., Watermark Research Partners; and scientific advisory board from Abbott

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The ADAPT-DES study (NCT00638794) was sponsored by the Cardiovascular Research Foundation (New York, New York) and funded by research grants from Boston Scientific, Abbott Vascular, Medtronic, Cordis, Biosensors, The Medicines Company, Daiichi-Sankyo, Eli Lilly, Volcano, and Accumetrics.

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