Muthiah Vaduganathan1, Robert A Harrington2, Gregg W Stone3, Efthymios N Deliargyris4, Ph Gabriel Steg5, C Michael Gibson6, Christian W Hamm7, Matthew J Price8, Alberto Menozzi9, Jayne Prats4, Steven Elkin4, Kenneth W Mahaffey2, Harvey D White10, Deepak L Bhatt11. 1. Brigham and Women's Hospital Heart & Vascular Center and Harvard Medical School, Boston, Massachusetts. 2. Stanford University Medical School, Stanford, California. 3. Columbia University Medical Center and the Cardiovascular Research Foundation, New York, New York. 4. The Medicines Company, Parsippany, New Jersey. 5. FACT (French Alliance for Cardiovascular clinical Trials), DHU FIRE, INSERM Unité 1148, Université Paris-Diderot, and Hôpital Bichat, Assistance-Publique-Hôpitaux de Paris, Paris, France; NHLI, Imperial College, Royal Brompton Hospital, London, United Kingdom. 6. Division of Cardiology, Beth Israel Deaconess Medical Center, Boston, Massachusetts. 7. Kerckhoff Heart and Thorax Center, Bad Nauheim, Germany. 8. Scripps Clinic and Scripps Translational Science Institute, La Jolla, California. 9. Azienda Ospedaliero-Universitaria di Parma, Parma, Italy. 10. Green Lane Cardiovascular Service, Auckland, New Zealand. 11. Brigham and Women's Hospital Heart & Vascular Center and Harvard Medical School, Boston, Massachusetts. Electronic address: dlbhattmd@post.harvard.edu.
Abstract
BACKGROUND:Cangrelor, an intravenous, reversible P2Y12 antagonist, is approved for use in patients undergoing percutaneous coronary intervention (PCI). OBJECTIVES: This study sought to evaluate the efficacy and safety of cangrelor compared with clopidogrel in subgroups that did and did not receive glycoprotein IIb/IIIa inhibitors (GPIs). METHODS: This pooled, patient-level analysis of the 3 CHAMPION (Cangrelor versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition) trials analyzed all randomized patients who underwent PCI and received the study drug (n = 24,902). Only bailout/rescue GPI use was permitted, except in CHAMPION PCI, in which routine or bailout/rescue GPI use was at the site investigator's discretion. The primary efficacy endpoint was the composite of all-cause mortality, myocardial infarction, ischemia-driven revascularization, or stent thrombosis at 48 h after randomization. RESULTS: Overall, 3,173 patients (12.7%) received a GPI, most commonly eptifibatide (69.4%). Despite variation in indications for GPIs, baseline characteristics were well balanced between the cangrelor and clopidogrel arms in subsets receiving and not receiving GPIs. Rates of the primary composite endpoint were lower with cangrelor compared with clopidogrel in patients who did (4.9% vs. 6.5%; odds ratio [OR]: 0.74; 95% confidence interval [CI]: 0.55 to 1.01) or did not receive a GPI (3.6% vs. 4.4%; OR: 0.82; 95% CI: 0.72 to 0.94; Pint = 0.55). Cangrelor did not increase the primary safety endpoint, GUSTO-defined severe/life-threatening bleeding, in patients who did (0.4% vs. 0.5%; OR: 0.71; 95% CI: 0.25 to 1.99) or did not receive GPIs (0.2% vs. 0.1%; OR: 1.56; 95% CI: 0.80 to 3.04; Pint = 0.21). GPI use was associated with increased risk of bleeding in both treatment arms. CONCLUSIONS:Cangrelor's efficacy in reducing ischemic complications in patients undergoing PCI was maintained irrespective of GPI administration. GPI use was associated with substantially higher bleeding rates, regardless of the randomization to cangrelor or clopidogrel. (A Clinical Trial to Demonstrate the Efficacy of Cangrelor [PCI]: NCT00305162; Cangrelor Versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition [PLATFORM]: NCT00385138; A Clinical Trial Comparing Cangrelor to Clopidogrel Standard Therapy in Subjects Who Require Percutaneous Coronary Intervention [PCI] [CHAMPION PHOENIX] [CHAMPION]: NCT01156571).
RCT Entities:
BACKGROUND:Cangrelor, an intravenous, reversible P2Y12 antagonist, is approved for use in patients undergoing percutaneous coronary intervention (PCI). OBJECTIVES: This study sought to evaluate the efficacy and safety of cangrelor compared with clopidogrel in subgroups that did and did not receive glycoprotein IIb/IIIa inhibitors (GPIs). METHODS: This pooled, patient-level analysis of the 3 CHAMPION (Cangrelor versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition) trials analyzed all randomized patients who underwent PCI and received the study drug (n = 24,902). Only bailout/rescue GPI use was permitted, except in CHAMPION PCI, in which routine or bailout/rescue GPI use was at the site investigator's discretion. The primary efficacy endpoint was the composite of all-cause mortality, myocardial infarction, ischemia-driven revascularization, or stent thrombosis at 48 h after randomization. RESULTS: Overall, 3,173 patients (12.7%) received a GPI, most commonly eptifibatide (69.4%). Despite variation in indications for GPIs, baseline characteristics were well balanced between the cangrelor and clopidogrel arms in subsets receiving and not receiving GPIs. Rates of the primary composite endpoint were lower with cangrelor compared with clopidogrel in patients who did (4.9% vs. 6.5%; odds ratio [OR]: 0.74; 95% confidence interval [CI]: 0.55 to 1.01) or did not receive a GPI (3.6% vs. 4.4%; OR: 0.82; 95% CI: 0.72 to 0.94; Pint = 0.55). Cangrelor did not increase the primary safety endpoint, GUSTO-defined severe/life-threatening bleeding, in patients who did (0.4% vs. 0.5%; OR: 0.71; 95% CI: 0.25 to 1.99) or did not receive GPIs (0.2% vs. 0.1%; OR: 1.56; 95% CI: 0.80 to 3.04; Pint = 0.21). GPI use was associated with increased risk of bleeding in both treatment arms. CONCLUSIONS:Cangrelor's efficacy in reducing ischemic complications in patients undergoing PCI was maintained irrespective of GPI administration. GPI use was associated with substantially higher bleeding rates, regardless of the randomization to cangrelor or clopidogrel. (A Clinical Trial to Demonstrate the Efficacy of Cangrelor [PCI]: NCT00305162; Cangrelor Versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition [PLATFORM]: NCT00385138; A Clinical Trial Comparing Cangrelor to Clopidogrel Standard Therapy in Subjects Who Require Percutaneous Coronary Intervention [PCI] [CHAMPION PHOENIX] [CHAMPION]: NCT01156571).
Authors: Heerajnarain Bulluck; Mervyn H H Chan; Jennifer A Bryant; Ping Chai; Ashish Chawla; Terrance S Chua; Yiu-Cho Chung; Gao Fei; Hee H Ho; Andrew F W Ho; Andrew J Hoe; Syed S Imran; Chi-Hang Lee; Swee H Lim; Boon W Liew; Patrick L Z Yun; Marcus O E Hock; Valeria Paradies; Matthew T Roe; Lynette Teo; Aaron S Wong; Evelyn Wong; Philip E Wong; Timothy Watson; Mark Y Chan; Jack W Tan; Derek J Hausenloy Journal: Clin Cardiol Date: 2018-12-17 Impact factor: 2.882
Authors: Davide Capodanno; Deepak L Bhatt; C Michael Gibson; Stefan James; Takeshi Kimura; Roxana Mehran; Sunil V Rao; Philippe Gabriel Steg; Philip Urban; Marco Valgimigli; Stephan Windecker; Dominick J Angiolillo Journal: Nat Rev Cardiol Date: 2021-08-23 Impact factor: 32.419
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