Platelet Reactivity and Clinical Outcomes After Coronary Artery Implantation of Drug-Eluting Stents (ADAPT-DES): A Prospective Multicenter Registry Study

Study Questions:

What is the relation between platelet reactivity during dual therapy with aspirin and clopidogrel and clinical outcomes after successful coronary drug-eluting stent implantation?

Methods:

ADAPT-DES was a prospective, multicenter registry of patients successfully treated with one or more drug-eluting stents and given aspirin and clopidogrel at 10-15 US and European hospitals. The investigators assessed platelet reactivity in those patients after successful percutaneous coronary intervention using VerifyNow point-of-care assays, and assigned different cutoffs to define high platelet reactivity. The primary endpoint was definite or probable stent thrombosis; other endpoints were all-cause mortality, myocardial infarction, and clinically relevant bleeding. Authors did a propensity-adjusted multivariable analysis to determine the relation between platelet reactivity and subsequent adverse events.

Results:

Between January 7, 2008, and September 16, 2010, 8,665 patients were prospectively enrolled at 11 sites, of which 8,583 were eligible. At 1-year follow-up, stent thrombosis had occurred in 70 (0.8%) patients, myocardial infarction in 269 (3.1%), clinically relevant bleeding in 531 (6.2%), and death in 161 (1.9%) patients. High platelet reactivity on clopidogrel was strongly related to stent thrombosis (adjusted hazard ratio [HR], 2.49; 95% confidence interval [CI], 1.43-4.31; p = 0.001) and myocardial infarction (adjusted HR, 1.42; 95% CI, 1.09-1.86; p = 0.01), was inversely related to bleeding (adjusted HR, 0.73; 95% CI, 0.61-0.89; p = 0.002), but was not related to mortality (adjusted HR, 1.20; 95% CI, 0.85-1.70; p = 0.30). High platelet reactivity on aspirin was not significantly associated with stent thrombosis (adjusted HR, 1.46; 95% CI, 0.58-3.64; p = 0.42), myocardial infarction, or death, but was inversely related to bleeding (adjusted HR, 0.65; 95% CI, 0.43-0.99; p = 0.04).

Conclusions:

The authors concluded that safer drugs or tailored strategies for the use of more potent agents must be developed if the benefits of greater platelet inhibition in patients with cardiovascular disease are to be realized.

Perspective:

The primary findings from the present study are that high platelet reactivity on clopidogrel was an independent predictor of 1-year stent thrombosis and myocardial infarction after drug-eluting stent placement, but was also protective against clinically relevant bleeding. Overall, the study confirms a strong independent relation between high platelet reactivity on clopidogrel and ischemic events at 30 days and 1 year, but also establishes an inverse correlation between high platelet reactivity and clinically relevant bleeding, consequently with a neutral effect on mortality. These findings emphasize the importance of hemorrhagic as well as ischemic complications, and suggest that safer drugs or tailored strategies for the use of more potent agents must be developed to attain the optimal benefits of greater platelet inhibition in patients with cardiovascular disease.

Clinical Topics: Invasive Cardiovascular Angiography and Intervention

Keywords: Myocardial Infarction, Platelet Aggregation Inhibitors, Thrombosis, Drug-Eluting Stents, Percutaneous Coronary Intervention


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