Wallentin L, Lindholm D, Siegbahn A, Wernroth L, Becker RC, Cannon CP, Cornel JH, Himmelmann A, Giannitsis E, Harrington RA, Held C, Husted S, Katus HA, Mahaffey KW, Steg PG, Storey RF, James SK; PLATO study group. Biomarkers in Relation to the Effects of Ticagrelor Compared with Clopidogrel in Non-ST-Elevation Acute Coronary Syndrome Patients Managed with or without In-Hospital Revascularization: A Substudy from the Prospective Randomized Platelet Inhibition and Patient Outcomes (PLATO) Trial. Circulation. 2013;129:293-303.

BACKGROUND: Risk stratification and the use of specific biomarkers have been proposed for tailoring treatment in patients with NSTE-ACS. We investigated the prognostic importance of hs-TnT, NT-proBNP and GDF-15 in relation to randomized treatment (ticagrelor vs. clopidogrel) and management strategy (with or without revascularization) in the NSTE-ACS subgroup of the PLATO trial.

METHODS AND RESULTS: Of 18,624 patients in the PLATO trial, 9,946 had an entry diagnosis of NSTE-ACS and baseline blood samples available. During index hospitalization, 5,357 were revascularized, and 4,589 managed without revascularization. Hs-TnT, NT-proBNP, and GDF-15 were determined and assessed according to predefined cut-off levels. Median follow-up was 9.1 months. Increasing levels of hs-TnT were associated with increasing risk of CV-death, MI and stroke in medically managed patients (p<0.001), but not in those managed invasively. NT-proBNP and GDF-15 levels were associated with the same events independent of management strategy. Ticagrelor vs. clopidogrel reduced the rate of CV-death, MI and stroke in patients with NSTE-ACS and hs-TnT ≥14.0 ng/L in both invasively and non-invasively managed patients; in patients with hs-TnT <14.0 ng/L there was no difference between ticagrelor and clopidogrel in the non-invasive group CONCLUSIONS: Hs-TnT, NT-proBNP and GDF-15 are predictors of CV-death, MI and stroke in patients with NSTE-ACS managed non-invasively and NT-proBNP and GDF-15 also in those managed invasively. Elevated hs-TnT predicts substantial benefit of ticagrelor over clopidogrel both in invasively and non-invasively managed patients, while no apparent benefit was seen at normal hs-TnT. CLINICAL TRIAL REGISTRATION INFORMATION: http://www.clinicaltrials.gov. Identifier: NCT00391872.

Trial: PLATO