Impact of reduced-dose prasugrel vs. standard-dose clopidogrel on in-hospital outcomes of percutaneous coronary intervention in 62 737 patients with acute coronary syndromes: a nationwide registry study in Japan.

In Japan, reduced-dose prasugrel (loading/maintenance dose, 20/3.75 mg) has been approved for use in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI), because of the higher bleeding risk among East Asians. However, its safety in the real-world population has not been investigated. We aimed to evaluate the effectiveness and safety of reduced-dose prasugrel vs. standard-dose clopidogrel in ACS patients undergoing PCI. Acute coronary syndrome patients who underwent PCI in 2016, who were treated with either reduced-dose prasugrel or standard-dose clopidogrel in addition to aspirin, were identified from the nationwide Japanese PCI registry. The primary outcome was in-hospital mortality following PCI. Secondary outcomes included stent thrombosis and bleeding complication after PCI. Among 62 737 ACS patients who underwent PCI at any of 986 participating centres across Japan (clopidogrel 31.9%; prasugrel 68.1%), we identified 12 016 propensity score-matched pairs (24 032 patients; age 69.4 ± 12.2 years; female 24.9%; ST-elevation myocardial infarction 42.3%). Compared with standard-dose clopidogrel, reduced-dose prasugrel was associated with increased risk of bleeding [odds ratio (OR) 1.65, 95% confidence interval (CI) 1.10-2.51; P = 0.016], but both had similar rates of mortality (OR 1.11, 95% CI 0.89-1.38; P = 0.371) and stent thrombosis (OR 1.29, 95% CI 0.73-2.30; P = 0.387) as well as similar falsification endpoints of cardiac tamponade and emergent operation. In Japanese ACS patients undergoing PCI, the risk of bleeding is higher when using reduced-dose prasugrel than when using standard-dose clopidogrel, but there is no significant difference in in-hospital mortality and incidence of stent thrombosis between the two antiplatelet regimens.

Akita K ，Inohara T ，Yamaji K ，Kohsaka S ，Numasawa Y ，Ishii H ，Amano T ，Kadota K ，Nakamura M ，Maekawa Y ... -  《-》

Ischemic and Bleeding Events Among Patients With Acute Coronary Syndrome Associated With Low-Dose Prasugrel vs Standard-Dose Clopidogrel Treatment.

Shoji S ，Sawano M ，Sandhu AT ，Heidenreich PA ，Shiraishi Y ，Ikemura N ，Ueno K ，Suzuki M ，Numasawa Y ，Fukuda K ，Kohsaka S ... -  《JAMA Network Open》

Associations Between Chronic Kidney Disease and Outcomes With Use of Prasugrel Versus Clopidogrel in Patients With Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention: A Report From the PROMETHEUS Study.

This study sought to compare clinical outcomes in a contemporary acute coronary syndrome (ACS) percutaneous coronary intervention (PCI) cohort stratified by chronic kidney disease (CKD) status. Patients with CKD exhibit high risks for both thrombotic and bleeding events, thus complicating decision making regarding antiplatelet therapy in the setting of ACS. The PROMETHEUS study was a multicenter observational study comparing outcomes with prasugrel versus clopidogrel in ACS PCI patients. Major adverse cardiac events (MACE) at 90 days and at 1 year were defined as a composite of death, myocardial infarction, stroke, or unplanned revascularization. Clinically significant bleeding was defined as bleeding requiring transfusion or hospitalization. Cox regression multivariable analysis was performed for adjusted associations between CKD status and clinical outcomes. Hazard ratios for prasugrel versus clopidogrel treatment were generated using propensity score stratification. The total cohort included 19,832 patients, 28.3% with and 71.7% without CKD. CKD patients were older with greater comorbidities including diabetes and multivessel disease. Prasugrel was less often prescribed to CKD versus non-CKD patients (11.0% vs. 24.0%, respectively; p < 0.001). At 1 year, CKD was associated with higher adjusted risk of MACE (1.27; 95% confidence interval: 1.18 to 1.37) and bleeding (1.46; 95% confidence interval: 1.24 to 1.73). Although unadjusted rates of 1-year MACE were lower with prasugrel versus clopidogrel in both CKD (18.3% vs. 26.5%; p < 0.001) and non-CKD (10.9% vs. 17.9%; p < 0.001) patients, associations were attenuated after propensity stratification. Similarly, unadjusted differences in 1-year bleeding with prasugrel versus clopidogrel (6.0% vs. 7.4%; p = 0.18 in CKD patients; 2.6% vs. 3.5%; p = 0.008 in non-CKD patients) were not significant after propensity score adjustment. Although risks for 1-year MACE were significantly higher in ACS PCI patients with versus without CKD, prasugrel use was 50% lower in patients with renal impairment. Irrespective of CKD status, outcomes associated with prasugrel use were not significant after propensity adjustment. These data highlight the need for randomized studies evaluating the optimal antiplatelet therapy in CKD patients with ACS.

Baber U ，Chandrasekhar J ，Sartori S ，Aquino M ，Kini AS ，Kapadia S ，Weintraub W ，Muhlestein JB ，Vogel B ，Faggioni M ，Farhan S ，Weiss S ，Strauss C ，Toma C ，DeFranco A ，Baker BA ，Keller S ，Effron MB ，Henry TD ，Rao S ，Pocock S ，Dangas G ，Mehran R ... -  《-》

Long versus short dual antiplatelet therapy in acute coronary syndrome patients treated with prasugrel or ticagrelor and coronary revascularization: Insights from the RENAMI registry.

D'Ascenzo F ，Bertaina M ，Fioravanti F ，Bongiovanni F ，Raposeiras-Roubin S ，Abu-Assi E ，Kinnaird T ，Ariza-Solé A ，Manzano-Fernández S ，Templin C ，Velicki L ，Xanthopoulou I ，Cerrato E ，Rognoni A ，Boccuzzi G ，Omedè P ，Montabone A ，Taha S ，Durante A ，Gili S ，Magnani G ，Autelli M ，Grosso A ，Blanco PF ，Garay A ，Quadri G ，Varbella F ，Queija BC ，Paz RC ，Fernández MC ，Pousa IM ，Gallo D ，Morbiducci U ，Dominguez-Rodriguez A ，Valdés M ，Cequier A ，Alexopoulos D ，Iñiguez-Romo A ，Gaita F ，Rinaldi M ，Lüscher TF ... -  《-》

Impact of low-dose prasugrel on platelet reactivity and cardiac dysfunction in acute coronary syndrome patients requiring primary drug-eluting stent implantation: A randomized comparative study.

The aim of this study was to compare how prasugrel and clopidogrel affect platelet aggregation reactivity, cardiac enzyme release, cardiac remodeling, and the formation of in-stent thrombi after primary percutaneous coronary intervention (PCI). The advantages of using prasugrel over clopidogrel in cardiac injury following acute coronary syndrome (ACS) remain unclear. A total of 78 ACS patients were randomly allocated into clopidogrel (300 mg loading/75 mg maintenance) or prasugrel (20 mg loading/3.75 mg maintenance) treatment groups, followed by undergoing primary PCI. Platelet reactivity and cardiac enzymes were measured before and after primary PCI. Moreover, cardiac function was measured by ultrasound echocardiography and coronary angioscopic observation was after primary PCI up to 8 months later. Antiplatelet reactivity in the prasugrel treatment group reached optimal levels (P2Y12 reaction units [PRU] less than 262) immediately after the administration and was maintained even at 8 months, independently of the CYP2C19 genotype. Prasugrel treatment significantly suppressed creatine kinase elevation compared to clopidogrel treatment (median value 404 IU/L to 726 IU/L vs. 189 IU/L to 1,736 IU/L, p = 0.018 for maximum values) and reduced left ventricular mass (217.2-168.8 g in prasugrel, p = 0.045; 196.9-176.4 g in clopidogrel, p = 0.061). There were no significant differences in the incidence of in-stent attached thrombi between the two groups. Compared to clopidogrel, prasugrel produced a stable platelet aggregation inhibitory effect in patients with ACS regardless of CYP2C19 genotype, reduced cardiac enzyme release, and prevented cardiac remodeling after ACS.

Kitano D ，Takayama T ，Fukamachi D ，Migita S ，Morikawa T ，Tamaki T ，Kojima K ，Mineki T ，Murata N ，Akutsu N ，Sudo M ，Hiro T ，Hirayama A ，Okumura Y ... -  《-》