Sergio Leonardi1, Renato D Lopes2, Ph Gabriel Steg3,4,5, Freddy Abnousi6, Alberto Menozzi7, Jayne Prats8, Stacey Mangum2, Matthew Wilson2, Meredith Todd8, Gregg W Stone9,10, C Michael Gibson11, Christian W Hamm12, Matthew J Price13,14, Harvey D White15, Robert A Harrington6, Deepak L Bhatt16,17, Kenneth W Mahaffey6. 1. 1 Fondazione IRCCS Policlinico San Matteo, Italy. 2. 2 Duke Clinical Research Institute, USA. 3. 3 FACT, DHU FIRE, INSERM U-1148, Paris, France. 4. 4 Université Paris-Diderot, France. 5. 5 Hôpital Bichat, Assistance-Publique-Hôpitaux de Paris, France. 6. 6 Department of Medicine, Stanford University, USA. 7. 7 Unità Operativa di Cardiologia, Azienda Ospedaliero-Universitaria di Parma, Italy. 8. 8 The Medicines Company, USA. 9. 9 Columbia University Medical Center, USA. 10. 10 Cardiovascular Research Foundation, USA. 11. 11 Division of Cardiology, Beth Israel Deaconess Medical Center, USA. 12. 12 Kerckhoff Heart and Thorax Center, Germany. 13. 13 Scripps Clinic, USA. 14. 14 Scripps Translational Science Institute, USA. 15. 15 Auckland City Hospital, Green Lane Cardiovascular Service, New Zealand. 16. 16 Brigham and Women's Hospital Heart and Vascular Center, USA. 17. 17 Harvard Medical School, USA.
Abstract
AIMS: The purpose of this study was to test whether different results between Cangrelor versus standard therapy to acHieve optimal Management of Platelet InhibitiON (CHAMPION) PCI/PLATFORM and PHOENIX trials are due in part to different definitions of percutaneous coronary intervention (PCI)-related myocardial infarction (MI). METHODS AND RESULTS: In patients with acute coronary syndrome (ACS), the definition of MI was identical in CHAMPION PCI and PLATFORM and did not require an assessment of baseline cardiac biomarker status, while in PHOENIX specific MI criteria were associated with different patient presentations. The same MI criteria were used in PCI, PLATFORM, and PHOENIX for patients with stable angina. Logistic regression assessed the effect of cangrelor on MI (PCI- and non-PCI related) in the combined PCI/PLATFORM population and in PHOENIX. Consistency of cangrelor's effect in PCI/PLATFORM and in PHOENIX in patients with stable angina and in those with an ACS (with or without ST elevation) was evaluated. Overall, the incidence of PCI-related MI at 48 h was 6.3% in PCI/PLATFORM and 4.0% in PHOENIX. In patients with ACS, MI incidence was 6.4% in PCI/PLATFORM and 1.7% in PHOENIX, and 6.3% and 5.6%, respectively in stable angina patients. Cangrelor's effect on PCI-related MI differed between PCI/PLATFORM (odds ratio (OR) 1.03, 95% confidence interval (CI) 0.90-1.17) and PHOENIX (OR 0.80, 95% CI 0.66-0.98) with pINT=0.04. This difference was mostly evident in patients with ACS ( pINT= 0.06) while the effect was consistent in patients with stable angina ( pINT=0.81). Results were similar when all MIs were analyzed. CONCLUSIONS: The definition of PCI-related MI has important implications for event rates, treatment effect, and study results. This illustrates the importance of a rigorous assessment of PCI-related MI in clinical trials of patients with an ACS.
RCT Entities:
AIMS: The purpose of this study was to test whether different results between Cangrelor versus standard therapy to acHieve optimal Management of Platelet InhibitiON (CHAMPION) PCI/PLATFORM and PHOENIX trials are due in part to different definitions of percutaneous coronary intervention (PCI)-related myocardial infarction (MI). METHODS AND RESULTS: In patients with acute coronary syndrome (ACS), the definition of MI was identical in CHAMPION PCI and PLATFORM and did not require an assessment of baseline cardiac biomarker status, while in PHOENIX specific MI criteria were associated with different patient presentations. The same MI criteria were used in PCI, PLATFORM, and PHOENIX for patients with stable angina. Logistic regression assessed the effect of cangrelor on MI (PCI- and non-PCI related) in the combined PCI/PLATFORM population and in PHOENIX. Consistency of cangrelor's effect in PCI/PLATFORM and in PHOENIX in patients with stable angina and in those with an ACS (with or without ST elevation) was evaluated. Overall, the incidence of PCI-related MI at 48 h was 6.3% in PCI/PLATFORM and 4.0% in PHOENIX. In patients with ACS, MI incidence was 6.4% in PCI/PLATFORM and 1.7% in PHOENIX, and 6.3% and 5.6%, respectively in stable anginapatients. Cangrelor's effect on PCI-related MI differed between PCI/PLATFORM (odds ratio (OR) 1.03, 95% confidence interval (CI) 0.90-1.17) and PHOENIX (OR 0.80, 95% CI 0.66-0.98) with pINT=0.04. This difference was mostly evident in patients with ACS ( pINT= 0.06) while the effect was consistent in patients with stable angina ( pINT=0.81). Results were similar when all MIs were analyzed. CONCLUSIONS: The definition of PCI-related MI has important implications for event rates, treatment effect, and study results. This illustrates the importance of a rigorous assessment of PCI-related MI in clinical trials of patients with an ACS.
Authors: Christoph B Olivier; Vandana Sundaram; Deepak L Bhatt; Sergio Leonardi; Renato D Lopes; Victoria Y Ding; Lingyao Yang; Gregg W Stone; Ph Gabriel Steg; C Michael Gibson; Christian W Hamm; Matthew J Price; Harvey D White; Manisha Desai; Donald R Lynch; Robert A Harrington; Kenneth W Mahaffey Journal: Int J Cardiol Date: 2018-06-08 Impact factor: 4.164
Authors: Sergio Leonardi; Anna Franzone; Raffaele Piccolo; Eugene McFadden; Pascal Vranckx; Patrick Serruys; Edouard Benit; Christoph Liebetrau; Luc Janssens; Maurizio Ferrario; Aleksander Zurakowski; Robert-Jan van Geuns; Marcello Dominici; Kurt Huber; Ton Slagboom; Paweł Buszman; Leonardo Bolognese; Carlo Tumscitz; Krzysztof Bryniarski; Adel Aminian; Mathias Vrolix; Ivo Petrov; Scot Garg; Christoph Naber; Janusz Prokopczuk; Christian Hamm; Gabriel Steg; Dik Heg; Peter Juni; Stephan Windecker; Marco Valgimigli Journal: BMJ Open Date: 2019-03-09 Impact factor: 2.692