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
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.
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
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