Abstract

Mahaffey KW, Held C, Wojdyla DM, James SK, Katus HA, Husted S, Steg PG, Cannon CP, Becker RC, Storey RF, Khurmi NS, Nicolau JC, Yu CM, Ardissino D, Budaj A, Morais J, Montgomery D, Himmelmann A, Harrington RA, Wallentin L; PLATO Investigators. Ticagrelor Effects on Myocardial Infarction and the Impact of Event Adjudication in the Platelet Inhibition and Patient Outcomes (PLATO) Trial. J Am Coll Cardiol. 2014;63:1493-9.

OBJECTIVES: This study reports 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, based on 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 end point. 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]: 0.75-0.95). Non-procedural MI (HR: 0.86; 95% CI: 0.74-1.01) 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 a numerical excess was observed in patients assigned ticagrelor. Analyses of overall MI using investigator-reported data showed similar results but did not reach statistical significance (HR: 0.88; 95% CI: 0.78-1.00).

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 end points compared with site investigators. CLINICAL TRIAL: NCT00391872.

Trial: PLATO