Abstract

effect (in-hospital all types of bleeding, 2.0% vs. 1.8%; 2-year bleeding requiring readmission, 1.4% vs. 2.3%). 6 These inconsistent results from the same registry might be attributed to patient selection (ACS vs. ACS/CCS, major teaching hospital vs. non-selected hospital, short-term vs. long-term follow-up, etc.).Therefore, its definitive superiority remains uncertain at this point.The recent Japanese guideline does not prioritize prasugrel over clopidogrel or vice versa for both ACS and CCS patients undergoing PCI. 8 The inconsistent findings of bleeding events would necessitate further investigation of optimizing antiplatelet strategy depending on the individual patient's background and time course after PCI. Prasugrel Monotherapy After PCI in Japanese PatientsThe Figure summarizes the trials investigating various short DAPT regimens.Short DAPT followed by P2Y12 receptor inhibitor monotherapy has become the mainstream of antithrombotic therapy after PCI.The superiority of the short DAPT strategy was consistently observed, even in complex PCI patients who are considered to be at high thrombotic risk. 9In both ACS and CCS patients, P2Y12 receptor inhibitor monotherapy after 1-3-month DAPT is recommended for patients with both high ischemic and high bleeding risk, as a Class IIa recommendation in the Japanese guidelines. 8The PENDULUM mono study 10 and REIWA registry 11 both investigated the safety of the short DAPT followed by prasugrel monotherapy and showed that the incidence rates of both ischemic and bleeding events were acceptably low (ischemic event: 3.8% and 2.25%, bleeding event: 3.20% and 1.08% at 1 year, respectively).The combined PENDULUM mono and PENDULUM registry further showed a trend of lower bleeding events without an increase in ischemic events with short DAPT (≤6 months) followed by prasugrel monotherapy compared with prolonged DAPT with prasugrel (12 months) in Japanese patients with high bleeding risk undergoing PCI, using an inverse probability of treatment weighting method DAPT With Prasugrel After PCI in Japanese PatientsPrasugrel is a potent P2Y12 receptor inhibitor and a first-line choice for acute coronary syndrome (ACS) in Western countries. 1Unlike clopidogrel, prasugrel is not affected by CYP2C19 metabolism, which, theoretically, makes it promising for Japanese patients who often possess CYP2C19 polymorphisms.However, the potent nature of prasugrel raises concerns about bleeding risks, particularly in the Japanese population, which is generally at higher risk for bleeding complications. 2 Based on Phase II trial results, prasugrel has been carefully adjusted and approved at a low dose in Japan, and is now widely used. 3The Table summarizes the evidence from low-dose prasugrel trials reported in Japan.The trials can be categorized into those evaluating dual antiplatelet therapy (DAPT) with prasugrel and those assessing prasugrel monotherapy.The only randomized controlled trials (RCTs) comparing DAPT with low-dose prasugrel to DAPT with clopidogrel are the PRASFIT-ACS and PRASFIT-Elective trials, 4,5 which were conducted for market approval.In those trials, the event rate of ischemic events, a composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal ischemic stroke within 24 weeks, was numerically lower in patients treated with low-dose prasugrel than in those treated with clopidogrel, in both ACS (9.4% vs. 11.8%) and elective percutaneous coronary intervention (PCI) populations (4.1% vs. 6.7%),without an increase in clinically serious bleeding events when used with aspirin.On the other hand, real-world observational studies consistently show comparable efficacy of low-dose prasugrel to clopidogrel.In this issue of the Journal, a study by Kuno et al. from the JCD-KiCS registry also demonstrate comparable efficacy and safety of DAPT with low-dose prasugrel to DAPT with clopidogrel after PCI in a 2-year follow-up (adjusted hazard ratio (HR) for ACS: 0.58, 95% confidence interval (CI): 0.29-1.16,adjusted HR for bleeding: 0.62, 95% CI: 0.29-1.32). 6Their previous study of short-term outcomes reported a hazardous effect of DAPT with prasugrel for bleeding risk (odds ratio for bleeding complications within 72 h after PCI: 2.91 95% CI: 1.63-6.18), 7whereas the present study did not show such an unfavorable