REDUCED IMMEDIATE ISCHEMIC EVENTS WITH CANGRELOR IN PCI USING THE UNIVERSAL DEFINITION OF MI: POOLED ANALYSIS OF THE CANGRELOR VERSUS STANDARD THERAPY TO ACHIEVE OPTIMAL MANAGEMENT OF PLATELET INHIBITION TRIALS

Abstract

Background: As time to PCI shortens in Acute Coronary Syndrome (ACS) care, establishing the benefit of novel therapies on ischemic events is challenging. We evaluated Cangrelor, an intravenous potent rapid- acting P2Y12 inhibitor in ACS patients undergoing PCI using the Universal Definition of MI in an analysis of the CHAMPION trials. Methods: The CHAMPION PLATFORM and PCI studies were parallel double-blind phase 3 trials comparing Cangrelor with Clopidogrel in PCI patients. Both studies had death, MI or ischemia-driven revascularization (IDR); (including stent thrombosis) at 48 hours as the primary endpoint. As the studies had similar inclusion/exclusion criteria, they were pooled. STEMI patients (pre-defined safety population) were excluded as recurrent MI could not be discriminated from the index MI. We applied the Universal Definition of MI (Type 4) to the Clinical Events Committee adjudicated MI. MI was defined as an elevation of CK-MB > 3x ULN if the baseline was stable/ falling, or new Q-waves. MI re-evaluation was blinded to treatment allocation. Results: 13049 patients were randomized to either Cangrelor or Clopidogrel. The median age was 62.5 years, while females and diabetics were 28% and 31.7% of the population, respectively. Major (TIMI or GUSTO) bleeding and transfusions were not increased with Cangrelor. Conclusions: Using the Universal Definition of MI, Cangrelor was associated with a significant reduction in early ischemic events when compared with Clopidogrel in PCI patients. Cangrelor N=6543 Clopidogrel N=6506 Odds Ratio (95% C.I.) P value Death/MI Universal Definition/IDR 203/6543 (3.1) 244/6506 (3.8) 0.82 (0.68,0.99) 0.0422 Death 14/6543 (0.2) 23/6506 (0.4) 0.60 (0.31,1.18) 0.1380 MI Universal Definition 172/6543 (2.6) 194/6506 (3.0) 0.88 (0.71,1.08) 0.2222 IDR 32/6543 (0.5) 47/6506 (0.7) 0.68 (0.43,1.06) 0.0878 Stent Thrombosis (ST) 12/6543 (0.2) 27/6506 (0.4) 0.44 (0.22,0.87) 0.0184 Death/MI Universal Definition/(ST) 190/6543 (2.9) 228/6506 (3.5) 0.82 (0.68, 1.00) 0.0517 MI original definition 455/6543 (7.0) 447/6506 (6.9) 1.01 (0.88, 1.16) 0.85100.8510