Pharmacodynamic Assessment of Platelet Reactivity After a Loading Dose of Prasugrel or Clopidogrel in Patients With ST-Segment Elevation Myocardial Infarction

Abstract

Background: Few studies have compared the platelet reactivity of prasugrel and clopidogrel in the acute phase of ST-segment elevation myocardial infarction (STEMI). Methods and Results:Primary percutaneous coronary intervention (PCI) was performed in 78 patients with STEMI within 12 h of onset. Patients were randomly assigned to receive a Japanese standard loading dose of prasugrel 20 mg or clopidogrel 300 mg. Platelet reactivity was serially assessed using the VerifyNow-P2Y12 assay, the results of which were expressed as P2Y12-reaction-units (PRU). PRU values were significantly lower in the prasugrel group (n=38) than in the clopidogrel group (n=40) at 3 h, 24 h, and 14 days after loading (191±101 vs. 271±50, 147±80 vs. 261±57, and 171±67 vs. 221±70, respectively, P<0.05), although the PRU levels at baseline (231±57 vs. 237±58, P=0.65) and 1 h after loading (282±65 vs. 291±62, P=0.54) were similar. As compared with the baseline values, the PRU levels at 1, 3 and 24 h after clopidogrel loading were significantly higher (respectively, P<0.05), whereas only the PRU at 1 h after prasugrel was elevated (P<0.001). Conclusions:In Japanese patients with STEMI who undergo primary PCI, prasugrel provides stronger platelet inhibition than clopidogrel from 3 h after loading, whereas platelet reactivity remained elevated within 24 h after clopidogrel loading. (Circ J 2016; 80: 2520 -2527

The Conundrum of Platelet P2Y₁₂ Inhibition in ST-Segment Elevation Myocardial Infarction

“…Interestingly, however, this was evident up to 24 h in patients treated with clopidogrel, perhaps because of the high number of patients with CYP2C19 loss-of-function alleles. The rates of HPR, defined as PRU >262 based on studies performed in Japanese populations, were numerically lower with prasugrel compared with clopidogrel at all time points, although the difference reached statistical significance only at 24 h. 6 Of note, 3 h post-LD, 36 patients treated with prasugrel still had HPR, which is in line with studies conducted in Western countries. 4, 7 Although the results of this study were overall anticipated because of the known pharmacological profiles of prasugrel and clopidogrel, the authors should be commended for their work as they have, for the first time, investigated this topic in Japanese patients, where different dosing regimens of P2Y12 receptor inhibitors are used.…”

“…5 In this issue of the Journal, Ichikawa and colleagues report their results of a study investigating the PD comparison of prasugrel and clopidogrel in STEMI patients. 6 In this study, 78 Japanese patients undergoing PPCI were randomly assigned to receive approved doses of either prasugrel (20 mg LD followed by 3.75 mg/day maintenance dose) or clopidogrel (300 mg LD followed by 75 mg/day maintenance dose). Platelet reactivity was measured by VerifyNow-P2Y12 at 5 time points: baseline, 1, 3 and 24 h after the LD and after 14 days of maintenance treatment.…”

Role of Platelet Activation and Oxidative Stress in the Evolution of Myocardial Infarction

“…96 In addition, these patients with STEMI have less time from diagnosis to angiography and are more likely to undergo percutaneous coronary intervention (PCI) after angiography. 97 Platelet P-selectin expression is substantially enhanced in patients with acute coronary syndrome (ACS), particularly in those with STEMI, and correlates with myocardial necrosis markers (troponin I and creatine kinase-MB). 98 –101…”

Platelet-Derived Thrombogenicity Measured by Total Thrombus-Formation Analysis System in Patients With ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention

“…Second, the onset of action of P2Y12 inhibitors is delayed in the setting of STEMI, and the effect is insufficient at the time of PPCI. 30, 31 In the present study, prasugrel provided lower PRU levels during PPCI than clopidogrel; however, PRU levels during PPCI were suboptimal in both therapy groups. The blood sampling timing (i.e., at the time of PPCI) may be too early to detect the effect of the loading of oral prasugrel and clopidogrel.…”