Kenneth W Mahaffey1, Claes Held2, Daniel M Wojdyla3, Stefan K James2, Hugo A Katus4, Steen Husted5, Philippe Gabriel Steg6, Christopher P Cannon7, Richard C Becker3, Robert F Storey8, Nardev S Khurmi9, José C Nicolau10, Cheuk-Man Yu11, Diego Ardissino12, Andrzej Budaj13, Joao Morais14, Debra Montgomery3, Anders Himmelmann15, Robert A Harrington16, Lars Wallentin2. 1. Duke Clinical Research Institute, Duke University, Durham, North Carolina; Department of Medicine, Stanford University, Stanford, California. Electronic address: kenneth.mahaffey@stanford.edu. 2. Department of Medical Sciences, Cardiology and Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden. 3. Duke Clinical Research Institute, Duke University, Durham, North Carolina. 4. Medizinishe Klinik, University of Heidelberg, Heidelberg, Germany. 5. Medical Department, Hospital Unit West, Herning/Holstbro, Denmark. 6. INSERM-Unité 698, Paris, France; Assistance Publique-Hôpitaux de Paris, Département Hospitalo-Universitaire FIRE, Hôpital Bichat, Paris, France; Université Paris-Diderot, Sorbonne-Paris Cité, Paris, France. 7. TIMI Study Group, Brigham and Women's Hospital, Boston, Massachusetts. 8. Department of Cardiovascular Science, University of Sheffield, Sheffield, United Kingdom. 9. AstraZeneca Research and Development, Wilmington, Delaware. 10. Heart Institute (InCor), University of São Paulo Medical School, São Paulo, Brazil. 11. Prince of Wales Hospital, Institute of Vascular Medicine, the Chinese University of Hong Kong, Hong Kong. 12. Azienda Ospedaliero Universitaria di Parma, Parma, Italy. 13. Postgraduate Medical School, Grochowski Hospital, Warsaw, Poland. 14. Santo Andrés Hospital, Leiria, Portugal. 15. AstraZeneca Research and Development, Mölndal, Sweden. 16. Department of Medicine, Stanford University, Stanford, California.
Abstract
OBJECTIVES: This study sought to report the treatment effect of ticagrelor on myocardial infarction (MI) and the strategy for and impact of event adjudication in the PLATO (Platelet Inhibition and Patient Outcomes) trial. BACKGROUND: In PLATO, ticagrelor reduced cardiovascular death, MI, or stroke in patients with acute coronary syndromes (ACS). METHODS: A clinical events committee (CEC) prospectively defined and adjudicated all suspected MI events, on the basis of events reported by investigators and by triggers on biomarkers. Treatment comparisons used CEC-adjudicated data, and per protocol, excluded silent MI. RESULTS: Overall, 1,299 (610 ticagrelor, 689 clopidogrel) MIs reported by the CEC occurred during the trial. Of these, 1,097 (504 ticagrelor, 593 clopidogrel) contributed to the primary composite endpoint. Site investigators reported 1,198 (580 ticagrelor, 618 clopidogrel) MIs. Ticagrelor significantly reduced overall MI rates (12-month CEC-adjudicated Kaplan-Meier rates: 5.8% ticagrelor, 6.9% clopidogrel; hazard ratio [HR]: 0.84; 95% confidence interval [CI]: 0.75 to 0.95). Nonprocedural MI (HR: 0.86; 95% CI: 0.74 to 1.01) and MI related to percutaneous coronary intervention or stent thrombosis tended to be lower with ticagrelor. MIs related to coronary artery bypass graft surgery were few, but numerical excess was observed in patients assigned ticagrelor. Analyses of overall MIs using investigator-reported data showed similar results but did not reach statistical significance (HR: 0.88; 95% CI: 0.78 to 1.00). CONCLUSIONS: In patients with ACS, ticagrelor significantly reduced the incidence of MI compared with clopidogrel, with consistent results across most MI subtypes. CEC procedures identified more MI endpoints compared with site investigators. (A Comparison of Ticagrelor [AZD6140] and Clopidogrel in Patients With Acute Coronary Syndrome [PLATO]; NCT00391872).
RCT Entities:
OBJECTIVES: This study sought to report the treatment effect of ticagrelor on myocardial infarction (MI) and the strategy for and impact of event adjudication in the PLATO (Platelet Inhibition and Patient Outcomes) trial. BACKGROUND: In PLATO, ticagrelor reduced cardiovascular death, MI, or stroke in patients with acute coronary syndromes (ACS). METHODS: A clinical events committee (CEC) prospectively defined and adjudicated all suspected MI events, on the basis of events reported by investigators and by triggers on biomarkers. Treatment comparisons used CEC-adjudicated data, and per protocol, excluded silent MI. RESULTS: Overall, 1,299 (610 ticagrelor, 689 clopidogrel) MIs reported by the CEC occurred during the trial. Of these, 1,097 (504 ticagrelor, 593 clopidogrel) contributed to the primary composite endpoint. Site investigators reported 1,198 (580 ticagrelor, 618 clopidogrel) MIs. Ticagrelor significantly reduced overall MI rates (12-month CEC-adjudicated Kaplan-Meier rates: 5.8% ticagrelor, 6.9% clopidogrel; hazard ratio [HR]: 0.84; 95% confidence interval [CI]: 0.75 to 0.95). Nonprocedural MI (HR: 0.86; 95% CI: 0.74 to 1.01) and MI related to percutaneous coronary intervention or stent thrombosis tended to be lower with ticagrelor. MIs related to coronary artery bypass graft surgery were few, but numerical excess was observed in patients assigned ticagrelor. Analyses of overall MIs using investigator-reported data showed similar results but did not reach statistical significance (HR: 0.88; 95% CI: 0.78 to 1.00). CONCLUSIONS: In patients with ACS, ticagrelor significantly reduced the incidence of MI compared with clopidogrel, with consistent results across most MI subtypes. CEC procedures identified more MI endpoints compared with site investigators. (A Comparison of Ticagrelor [AZD6140] and Clopidogrel in Patients With Acute Coronary Syndrome [PLATO]; NCT00391872).
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