Comparison of Prasugrel and Ticagrelor Loading Doses in ST-Segment Elevation Myocardial Infarction Patients RAPID (Rapid Activity of Platelet Inhibitor Drugs) Primary PCI Study

Objectives This study sought to compare the action of prasugrel and ticagrelor in ST-segment elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PPCI). Background It has been documented that prasugrel and ticagrelor are able to provide effective platelet inhibition 2 h after a loading dose (LD). However, the pharmacodynamic measurements after prasugrel and ticagrelor LD have been provided by assessing only healthy volunteers or subjects with stable coronary artery disease. Methods Fifty patients with STEMI undergoing PPCI with bivalirudin monotherapy were randomized to receive 60 mg prasugrel LD (n = 25) or 180 mg ticagrelor LD (n = 25). Residual platelet reactivity was assessed by VerifyNow at baseline and 2, 4, 8, and 12 h after LD. Results Platelet reactivity units (PRU) 2 h after the LD (study primary endpoint) were 217 (12 to 279) and 275 (88 to 305) in the prasugrel and ticagrelor groups, respectively (p = NS), satisfying pre-specified noninferiority criteria. High residual platelet reactivity (HRPR) (PRU >= 240) was found in 44% and 60% of patients (p = 0.258) at 2 h. The mean time to achieve a PRU >= 240 was 3 +/- 2 h and 5 +/- 4 h in the prasugrel and ticagrelor groups, respectively. The independent predictors of HRPR at 2 h were morphine use (odds ratio: 5.29; 95% confidence interval: 1.44 to 19.49; p = 0.012) and baseline PRU value (odds ratio: 1.014; 95% confidence interval: 1.00 to 1.03; p = 0.046). Conclusions In patients with STEMI, prasugrel showed to be noninferior as compared with ticagrelor in terms of residual platelet reactivity 2 h after the LD. The 2 drugs provide an effective platelet inhibition 2 h after the LD in only a half of patients, and at least 4 h are required to achieve an effective platelet inhibition in the majority of patients. Morphine use is associated with a delayed activity of these agents. (Rapid Activity of Platelet Inhibitor Drugs Study, NCT01510171) (J Am Coll Cardiol 2013;61:1601-6) (c) 2013 by the American College of Cardiology Foundation