Selecting antiplatelet therapy at the time of percutaneous intervention for an acute coronary syndrome: weighing the benefits and risks of prasugrel versus clopidogrel.

BACKGROUND On average, acute coronary syndrome patients treated with prasugrel experience fewer ischemic complications, but more bleeding, than those receiving clopidogrel. However, heterogeneity in treatment effects can alter the likelihood of benefits and risks of an individual patient. We developed predictive models of the benefits (reduced ischemic events) and risks (increased bleeding) to support targeting prasugrel to those who benefit most from treatment. METHODS AND RESULTS Using 12 579 patients from Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel-Thrombolysis in Myocardial Infarction 38 (TRITON-TIMI 38), we fit risk models for ischemic events (cardiovascular death, spontaneous myocardial infarction, stroke) and bleeding (TIMI major/minor) over a 14.8-month follow-up and then calculated each patient's predicted risk for major ischemia and bleeding with both prasugrel and clopidogrel. We found substantial heterogeneity of the treatment effect of prasugrel (mean absolute reduction in the ischemia risk with prasugrel=1.5±3.0%, ranging from an 8.4% increased risk to a 31.2% reduction in risk for ischemia compared with clopidogrel). The mean absolute increase in the bleeding risk with prasugrel versus clopidogrel was 1.3±1.4% and ranged from a 7.9% lower risk to an 11.2% higher risk with prasugrel. The ratio of the difference in predicted ischemia risk/difference in predicted bleeding risk between prasugrel and clopidogrel was calculated for each patient to identify the proportion likely to benefit from prasugrel. Considering both ischemia and bleeding risk, a large proportion of TRITON participants (42%) were predicted to experience net benefit with prasugrel, a rate that increased if patients more strongly preferred avoiding ischemic events than bleeding. CONCLUSIONS The expected benefits and risks of prasugrel versus clopidogrel depend highly on patient characteristics. The use of risk models could support individualized thienopyridine selection to maximize the benefits and safety of these drugs.