TCT-4 Efficacy and Safety of Concurrent Administration of Clopidogrel-loading (600mg) and Prasugrel-loading (60mg) in Patients with Acute ST-Segment Elevation Myocardial Infarction

Abstract

Background: Current STEMI guideline recommendations limit the use of prasugrel to clopidogrel-naive patients. However, in daily clinical practice a considerable proportion of STEMI patients undergoing primary PCI are preloaded with clopidogrel. Whether the use of prasugrel in clopidogrel pretreated STEMI patients is safe remains unknown. Similarly, the efficacy of a combined loading dose regimen has not been evaluated. Methods: Between 1 September 2009 and 15 October 2012, a total of 1,157 STEMI patients were included in the randomized COMFORTABLE AMI trial (NCT 00962416) and 891 STEMI patients in the SPUM ACS registry (NCT 01000701) at 12 centers. Patients were divided into three groups according to type of peri-procedural antiplatelet loading: (1) Clopidogrel and subsequent Prasugrel loading dose [CP], (2) Prasugrel loading dose alone [P] (3) Clopidogrel loading dose alone [C]; 23 patients were excluded because they were not exposed to Clopidogrel and Prasugrel. The primary safety endpoint was the rate of BARC type 3, 4 and 5 bleeding at 30 days. The primary efficacy endpoint was the composite of cardiac death, nonfatal MI and nonfatal stroke at 30 days. Outcomes were analyzed using Cox's Regressions (crude) and multinomial ITPW weighted Cox's Regressions. Results: A total of 2,025 patients were analysed of whom 428 (21.1%) had received CP, 447 (22.1%) patients P alone, and 1,150 (56.8%) patients C alone. The primary safety endpoint was observed among 1.2% of CP, 1.6% of P, and 1.5% of C patients (CP vs C ad. HR 0.99 (0.36-2.72), PC vs P ad. HR 0.73 (0.22-2.41). The primary safety endpoint occurred less frequently among CP (1.9%) compared with C patients (5.0%, adjusted HR 0.47 (0.22-1.00), but with similar frequency among P and C patients (2.9% vs 5.0%, ad. HR 0.68 (0.27-1.73). The net clinical benefit outcome parameter tended to be lower among CP (2.8%) compared with C patients (6.3%, ad. HR 0.56 (0.30-1.05), whereas no significant difference was observed between P and C patients (3.8% vs 6.3%, ad. HR 0.85 (0.39-1.86). Conclusions: Among STEMI patients preloaded with Clopidogrel, the concurrent administration of a Prasugrel loading dose appears safe and potentially more effective than Clopiogrel alone.