Associations Between Complex PCI and Prasugrel or Clopidogrel Use in Patients With Acute Coronary Syndrome Who Undergo PCI: From the PROMETHEUS Study.

Potent P2Y12 inhibitors might offer enhanced benefit against thrombotic events in complex percutaneous coronary intervention (PCI). We examined prasugrel use and outcomes according to PCI complexity, as well as analyzing treatment effects according to thienopyridine type. PROMETHEUS was a multicentre observational study that compared clopidogrel vs prasugrel in acute coronary syndrome patients who underwent PCI (n = 19,914). Complex PCI was defined as PCI of the left main, bifurcation lesion, moderate-severely calcified lesion, or total stent length ≥ 30 mm. Major adverse cardiac events (MACE) were a composite of death, myocardial infarction, stroke, or unplanned revascularization. Outcomes were adjusted using multivariable Cox regression for effect of PCI complexity and propensity-stratified analysis for effect of thienopyridine type. The study cohort included 48.9% (n = 9735) complex and 51.1% (n = 10,179) noncomplex patients. Second generation drug-eluting stents were used in 70.1% complex and 66.2% noncomplex PCI patients (P < 0.0001). Complex PCI was associated with greater adjusted risk of 1-year MACE (hazard ratio [HR], 1.29; 95% confidence interval [CI], 1.20-1.39; P < 0.001). Prasugrel was prescribed in 20.7% of complex and 20.1% of noncomplex PCI patients (P = 0.30). Compared with clopidogrel, prasugrel significantly decreased adjusted risk for 1-year MACE in complex PCI (HR, 0.79; 95% CI, 0.68-0.92) but not noncomplex PCI (HR, 0.91; 95% CI, 0.77-1.08), albeit there was no evidence of interaction (P interaction = 0.281). Despite the use of contemporary techniques, acute coronary syndrome patients who undergo complex PCI had significantly higher rates of 1-year MACE. Adjusted magnitude of treatment effects with prasugrel vs clopidogrel were consistent in complex and noncomplex PCI without evidence of interaction.

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

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 ... -  《-》

Optimizing P2Y12 receptor inhibition in patients with acute coronary syndrome on the basis of platelet function testing: impact of prasugrel and high-dose clopidogrel.

This study sought to evaluate the impact of treatment with prasugrel and high-dose clopidogrel on the basis of platelet function testing in patients with acute coronary syndrome (ACS) who are undergoing percutaneous coronary intervention (PCI). The clinical impact of treatment with prasugrel in patients with ACS who have high platelet reactivity (HPR) is unknown. Patients with ACS who were pre-treated with clopidogrel and undergoing successful PCI were enrolled in a single-center, prospective registry. Platelet function was measured 12 to 36 h after PCI with the Multiplate device (Roche Diagnostics GmbH, Mannheim, Germany). Patients with HPR (>46 U) were switched to prasugrel or treated with high-dose clopidogrel, and those without HPR continued treatment with 75 mg of clopidogrel. A total of 741 consecutive patients were enrolled in the study between September 2011 and August 2012, and 219 of these patients (29.5%) had HPR. Although platelet reactivity decreased after treatment adjustments in those with HPR, prasugrel provided significantly more potent platelet inhibition compared with high-dose clopidogrel (p < 0.0001). Compared with patients without HPR, the risk of all-cause death, myocardial infarction, stent thrombosis, or stroke at 1 year was significantly higher in the high-dose clopidogrel group (hazard ratio [HR]: 2.27; 95% confidence interval [CI]: 1.45 to 3.55; p < 0.0001), and patients who were switched to prasugrel had similar outcomes (HR: 0.90; 95% CI: 0.44 to 1.81; p = 0.76). Bleeding Academic Research Consortium (BARC) type 3/5 bleeding was also more frequent in patients treated with high-dose clopidogrel (HR: 2.09; 95% CI: 1.05 to 4.17; p = 0.04) than in patients switched to prasugrel (HR: 0.45; 95% CI: 0.11 to 1.91; p = 0.28). In a multivariate model, HPR with high-dose clopidogrel, but not with prasugrel, was an independent predictor of the composite ischemic endpoint (HR: 1.90; 95% CI: 1.17 to 3.08; p = 0.01). Switching patients with ACS who have HPR to treatment with prasugrel reduces thrombotic and bleeding events to a level similar to that of those without HPR; however, there is a higher risk of both thrombotic and bleeding complications with high-dose clopidogrel.

Aradi D ，Tornyos A ，Pintér T ，Vorobcsuk A ，Kónyi A ，Faluközy J ，Veress G ，Magyari B ，Horváth IG ，Komócsi A ... -  《-》

Sex-related differences in outcomes among men and women under 55 years of age with acute coronary syndrome undergoing percutaneous coronary intervention: Results from the PROMETHEUS study.

Young women undergoing percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) experience greater adverse events than men, potentially due to under-treatment. We sought to compare the 1-year outcomes by sex in patients ≤55 years of age from a contemporary PCI cohort. PROMETHEUS was a retrospective multicenter observational US study comparing outcomes in clopidogrel and prasugrel treated patients following ACS PCI. MACE was defined as a composite of death, myocardial infarction, stroke or unplanned revascularization. Clinically significant bleeding was defined as bleeding requiring transfusion or hospitalization. Hazard ratios were generated using multivariable Cox proportional hazards regression. The study cohort included 4,851 patients of which 1,162 (24.0%) were women and 3,689 (76.0%) were men. In this cohort, the prevalence of diabetes (41.0 vs. 27.9%) and chronic kidney disease (12.7 vs. 7.2%) was higher among women compared with men. Irrespective of sex, prasugrel was used in less than one-third of patients (31.8% in men vs. 28.1% in women, P = 0.01). Unadjusted, 1-year MACE (21.1% vs. 16.2%, P < 0.001) and bleeding (3.6% vs. 2.2%, P = 0.01) was significantly higher in women compared with men, but these results were no longer significant after adjustment for risk (HR 1.13, 95% CI 0.94-1.36 for MACE and HR 1.31, 95% CI 0.85-2.04 for bleeding). Women ≤ 55 years of age undergoing ACS PCI have significantly greater comorbidities than young men. Despite a higher risk clinical phenotype in women, prasugrel use was significantly lower in women than men. Female sex was associated with a significantly higher risk of 1-year MACE and bleeding than male sex, findings that are attributable to baseline differences. © 2016 Wiley Periodicals, Inc.

Chandrasekhar J ，Baber U ，Sartori S ，Faggioni M ，Aquino M ，Kini A ，Weintraub W ，Rao S ，Kapadia S ，Weiss S ，Strauss C ，Toma C ，Muhlestein B ，DeFranco A ，Effron M ，Keller S ，Baker B ，Pocock S ，Henry T ，Mehran R ... -  《-》

Intensive oral antiplatelet therapy for reduction of ischaemic events including stent thrombosis in patients with acute coronary syndromes treated with percutaneous coronary intervention and stenting in the TRITON-TIMI 38 trial: a subanalysis of a randomi

Wiviott SD ，Braunwald E ，McCabe CH ，Horvath I ，Keltai M ，Herrman JP ，Van de Werf F ，Downey WE ，Scirica BM ，Murphy SA ，Antman EM ，TRITON-TIMI 38 Investigators ... -  《-》