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Platelet Reactivity and Risk of Stroke
Study Questions:
What is the association between P2Y12 reaction units (PRUs) and the risk of ischemic stroke (IS) after successful coronary drug-eluting stent (DES) implantation?
Methods:
The investigators evaluated the incidence, predictors, and prognostic impact of IS among patients enrolled in the multicenter, prospective ADAPT-DES (Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents) study. By protocol, patients were maintained on aspirin for 2 years and clopidogrel for at least 1 year. Baseline platelet reactivity on clopidogrel and aspirin were assessed by means of VerifyNow point-of-care assay after successful DES implantation. Adjusted hazard ratio (aHR) to evaluate the association between PRUs, aspirin reaction units (ARUs), and IS was obtained with multivariable Cox regression modeling.
Results:
Among 8,582 patients enrolled, 68 (0.8%) had an IS during 2-year follow-up. Across the spectrum of PRU, rates of IS were progressively greater as patients transitioned from the lowest quintile of PRU (more P2Y12-receptor inhibition; 2-year rate of 0.51%) to the highest quintile of PRU (less P2Y12-receptor inhibition; 2-year rate of 1.34%; adjusted p = 0.04). PRU >208 was independently associated with higher risk of IS at 2 years (aHR, 1.81; 95% confidence interval, 1.08-3.04; p = 0.03). The association between higher PRUs and risk for IS was also consistent in patients with versus without high CHA2DS2-VASc score (Pinteraction = 0.30), and in those on or off oral anticoagulation at discharge (Pinteraction = 0.99). Occurrence of IS was strongly associated with increased risk of all-cause mortality at 2 years.
Conclusions:
The authors concluded that higher PRU was associated with increased risk of IS after coronary DES implantation.
Perspective:
This study reports that PRU is independently associated with risk of IS at 2 years, which was consistent after adjusting for baseline stroke risk. Furthermore, the observed risk of IS was progressively greater across the spectrum of residual P2Y12-receptor inhibition, with the lowest risk in patients in the lowest quintile of PRU (more P2Y12-receptor inhibition) and the greatest risk in those in the highest quintile of PRU (less P2Y12-receptor inhibition), and ARU does not seem to be associated with increased risk of IS or hemorrhagic stroke. Additional prospective studies are indicated to assess whether or not ensuring optimal platelet inhibition reduces the risk for IS in patients with atherosclerotic cardiovascular disease.
Keywords: Aspirin, Blood Platelets, Brain Ischemia, Drug-Eluting Stents, Platelet Aggregation Inhibitors, Point-of-Care Systems, Primary Prevention, Risk, Stroke, Vascular Diseases
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