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.
- Received June 21, 2013.
- Revision received August 28, 2013.
- Accepted September 9, 2013.