Christoph B Olivier1,2, Deepak L Bhatt3, Sergio Leonardi4, Gregg W Stone5, C Michael Gibson6, Ph Gabriel Steg7, Christian W Hamm8, Matthew D Wilson9, Stacey Mangum9, Matthew J Price10, Jayne Prats11, Harvey D White12, Renato D Lopes9, Robert A Harrington13, Kenneth W Mahaffey1. 1. Stanford Center for Clinical Research, Department of Medicine, Stanford University School of Medicine, CA (C.B.O., K.W.M.). 2. Department of Cardiology and Angiology I, Heart Center Freiburg University, Faculty of Medicine, University of Freiburg, Germany (C.B.O.). 3. Brigham and Women's Hospital Heart & Vascular Center, Harvard Medical School, Boston, MA (D.L.B.). 4. University of Pavia, Fondazione IRCCS Policlinico S. Matteo, Pavia, Italy (S.L.). 5. Columbia University Medical Center and the Cardiovascular Research Foundation, New York City, NY (G.W.S.). 6. Beth Israel Deaconess Medical Center, Division of Cardiology, Boston, MA (C.M.G.). 7. 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, and NHLI, Imperial College, Royal Brompton Hospital, London, United Kingdom (P.G.S.). 8. Kerckhoff Heart and Thorax Center, Bad Nauheim, Germany (C.W.H.). 9. Duke University Medical Center, Durham, NC (M.D.W., S.M., R.D.L.). 10. Scripps Clinic and Scripps Translational Science Institute, La Jolla, CA (M.J.P.). 11. Elysis Llc, Carlisle, MA (J.P.). 12. Green Lane Cardiovascular Service, Auckland, New Zealand (H.D.W.). 13. Department of Medicine, Stanford University School of Medicine, Stanford, CA (R.A.H.).
Abstract
BACKGROUND: In the CHAMPION PHOENIX trial, cangrelor reduced the primary composite end point of death, myocardial infarction (MI), ischemia-driven revascularization, or stent thrombosis at 48 hours. This study aimed to explore the impact of event adjudication and the prognostic importance of MI reported by a clinical events committee (CEC) or site investigators (SIs). METHODS AND RESULTS: Data from the CHAMPION PHOENIX trial of patients undergoing elective or nonelective percutaneous coronary intervention were analyzed. A CEC systematically identified and adjudicated MI using predefined criteria, a computer algorithm to identify suspected events, and semilogarithmic plots to review biomarker changes. Thirty-day death was modeled using baseline characteristics. Of 10 942 patients, 462 (4.2%) patients had at least 1 MI by 48 hours identified by the CEC (207 [3.8%] cangrelor; 255 [4.7%] clopidogrel; odds ratio [OR] 0.80; 95% CI, 0.67-0.97; P=0.022), and 143 patients had at least 1 MI by 48 hours reported by the SI (60 [1.1%] cangrelor; 83 [1.5%] clopidogrel; OR, 0.72; 95% CI, 0.52-1.01; P=0.053). Of the 462 MIs identified by the CEC, 92 (20%) were reported by SI, and 370 (80%) were not. Of the 143 MI reported by the SI, 51 (36%) were not confirmed by CEC. All categories were associated with an increased adjusted risk for 30-day death (CEC: OR, 5.35; 95% CI, 2.56-11.2; P<0.001; SI: 9.08 [4.01-20.5]; P<0.001; CEC and SI: 10.9 [3.23-36.6]; P<0.001; CEC but not SI: 4.69 [1.94-11.3]; P<0.001; SI but not CEC: 15.4 [5.26-44.9]; P<0.001). CONCLUSIONS: In patients undergoing percutaneous coronary intervention, CEC procedures identified 3 times as many MIs as the SI reported. Compared with clopidogrel, cangrelor significantly reduced MIs identified by the CEC with a qualitatively similar relative risk reduction in MIs reported by the SI. MIs identified by CEC or reported by SI were independently associated with worse 30-day death. Central adjudication identified additional, prognostically important events. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01156571.
BACKGROUND: In the CHAMPION PHOENIX trial, cangrelor reduced the primary composite end point of death, myocardial infarction (MI), ischemia-driven revascularization, or stent thrombosis at 48 hours. This study aimed to explore the impact of event adjudication and the prognostic importance of MI reported by a clinical events committee (CEC) or site investigators (SIs). METHODS AND RESULTS: Data from the CHAMPION PHOENIX trial of patients undergoing elective or nonelective percutaneous coronary intervention were analyzed. A CEC systematically identified and adjudicated MI using predefined criteria, a computer algorithm to identify suspected events, and semilogarithmic plots to review biomarker changes. Thirty-day death was modeled using baseline characteristics. Of 10 942 patients, 462 (4.2%) patients had at least 1 MI by 48 hours identified by the CEC (207 [3.8%] cangrelor; 255 [4.7%] clopidogrel; odds ratio [OR] 0.80; 95% CI, 0.67-0.97; P=0.022), and 143 patients had at least 1 MI by 48 hours reported by the SI (60 [1.1%] cangrelor; 83 [1.5%] clopidogrel; OR, 0.72; 95% CI, 0.52-1.01; P=0.053). Of the 462 MIs identified by the CEC, 92 (20%) were reported by SI, and 370 (80%) were not. Of the 143 MI reported by the SI, 51 (36%) were not confirmed by CEC. All categories were associated with an increased adjusted risk for 30-day death (CEC: OR, 5.35; 95% CI, 2.56-11.2; P<0.001; SI: 9.08 [4.01-20.5]; P<0.001; CEC and SI: 10.9 [3.23-36.6]; P<0.001; CEC but not SI: 4.69 [1.94-11.3]; P<0.001; SI but not CEC: 15.4 [5.26-44.9]; P<0.001). CONCLUSIONS: In patients undergoing percutaneous coronary intervention, CEC procedures identified 3 times as many MIs as the SI reported. Compared with clopidogrel, cangrelor significantly reduced MIs identified by the CEC with a qualitatively similar relative risk reduction in MIs reported by the SI. MIs identified by CEC or reported by SI were independently associated with worse 30-day death. Central adjudication identified additional, prognostically important events. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01156571.
Authors: Neel M Butala; Jordan B Strom; Kamil F Faridi; Dhruv S Kazi; Yuansong Zhao; J Matthew Brennan; Jeffrey J Popma; Changyu Shen; Robert W Yeh Journal: JACC Cardiovasc Interv Date: 2020-07-15 Impact factor: 11.195
Authors: Eric L Eisenstein; Meredith N Zozus; Sharon F Terry; Linda Davidson-Ray; Kevin J Anstrom Journal: Ther Innov Regul Sci Date: 2021-07-06 Impact factor: 1.778
Authors: Neel M Butala; Kamil F Faridi; Eric A Secemsky; Yang Song; Jeptha Curtis; Charles Michael Gibson; Dhruv Kazi; Changyu Shen; Robert W Yeh Journal: J Am Heart Assoc Date: 2021-03-06 Impact factor: 5.501