Onset of antiplatelet action with high (100 mg) versus standard (60 mg) loading dose of prasugrel in patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention: pharmacodynamic study.

BACKGROUND In patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention, a suboptimal degree of platelet inhibition for the first 2 hours after the standard 60 mg loading dose of prasugrel has been described. METHODS AND RESULTS In a prospective, 3-center, nonrandomized, controlled study, 2 sequential groups of P2Y12 inhibitor-naive consecutive patients were loaded with either 100 mg (n=47) or 60 mg (n=35) of prasugrel. Platelet reactivity was assessed by VerifyNow at hours 0, 0.5, 1, 2, and 4. At hour 2, there was a strong trend for the primary end point of platelet reactivity (in P2Y12 reaction units) to be lower (least squares estimates of the mean difference [95% confidence interval], -45.5 [-91.2 to 0.3]; P=0.051), whereas platelet reactivity percentage inhibition (median, first to third quartile) was higher (75.5% [24%-91.8%] versus 23.5% [0%-78.3%]; P=0.02) in the 100-mg compared with 60-mg loading dose group. At hour 2, prasugrel 100 mg over 60 mg loading dose significantly reduced high platelet reactivity rates from 28.6% to 8.5% (≥230 P2Y12 reaction units threshold; P=0.036) and from 31.4% to 10.6% (≥208 P2Y12 reaction units threshold; P=0.024), whereas resulted in lower rate of ≤20% platelet inhibition (23.4% versus 51.4%; P=0.009). CONCLUSIONS In patients with ST-segment-elevation myocardial infarction treated with primary percutaneous coronary intervention, a higher (100 mg) than the standard loading dose of prasugrel results in greater and more consistent platelet inhibition, yet this will need to be further validated in additional studies. CLINICAL TRIAL REGISTRATION URL http://www.clinicaltrials.gov. Unique identifier: NCT01835353.