Biomarkers in relation to the effects of ticagrelor in comparison 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.

Abstract

BACKGROUND:

Risk stratification and the use of specific biomarkers have been proposed for tailoring treatment in patients with non-ST-elevation acute coronary syndrome (NSTE-ACS). We investigated the prognostic importance of high-sensitivity troponin T (hs-TnT), N-terminal pro-brain natriuretic peptide (NT-proBNP), and growth differentiation factor-15 (GDF-15) in relation to randomized treatment (ticagrelor versus clopidogrel) and management strategy (with or without revascularization) in the NSTE-ACS subgroup of the Platelet Inhibition and Patient Outcomes (PLATO) trial.

METHODS AND RESULTS:

Of 18 624 patients in the PLATO trial, 9946 had an entry diagnosis of NSTE-ACS and baseline blood samples available. During index hospitalization, 5357 were revascularized, and 4589 were managed without revascularization. Hs-TnT, NT-proBNP, and GDF-15 were determined and assessed according to predefined cutoff levels. Median follow-up was 9.1 months. Increasing levels of hs-TnT were associated with increasing risk of cardiovascular death, myocardial infarction, 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 versus clopidogrel reduced the rate of cardiovascular death, myocardial infarction, and stroke in patients with NSTE-ACS and hs-TnT ≥14.0 ng/L in both invasively and noninvasively managed patients; in patients with hs-TnT <14.0 ng/L, there was no difference between ticagrelor and clopidogrel in the noninvasive group

CONCLUSIONS:

Hs-TnT, NT-proBNP, and GDF-15 are predictors of cardiovascular death, myocardial infarction, and stroke in patients with NSTE-ACS managed noninvasively, 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 noninvasively managed patients, but no apparent benefit was seen at normal hs-TnT.

CLINICAL TRIAL REGISTRATION:

URL:http://www.clinicaltrials.gov. Unique identifier: NCT00391872.

• Authors: Lars Wallentin, Daniel Lindholm, Agneta Siegbahn, Lisa Wernroth, Richard C Becker, Christopher P Cannon, Jan H Cornel, Anders Himmelmann, Evangelos Giannitsis, Robert A Harrington, Claes Held, Steen Husted, Hugo A Katus, Kenneth W Mahaffey, Ph Gabriel Steg, Robert F Storey, Stefan K James, PLATO study group
• Journal: Circulation (Circulation) Vol. 129 Issue 3 Pg. 293-303 (Jan 21 2014) ISSN: 1524-4539 [Electronic] United States
• PMID: 24170388 (Publication Type: Comparative Study, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• GDF15 protein, human
• Growth Differentiation Factor 15
• Peptide Fragments
• Purinergic P2Y Receptor Antagonists
• Troponin T
• pro-brain natriuretic peptide (1-76)
• Natriuretic Peptide, Brain
• Clopidogrel
• Ticagrelor
• Adenosine
• Ticlopidine

Topics

• Acute Coronary Syndrome (blood, drug therapy, mortality)
• Adenosine (administration & dosage, analogs & derivatives)
• Biomarkers (blood)
• Clopidogrel
• Electrocardiography
• Growth Differentiation Factor 15 (blood)
• Hospital Mortality
• Humans
• Kaplan-Meier Estimate
• Myocardial Revascularization (mortality)
• Natriuretic Peptide, Brain (blood)
• Peptide Fragments (blood)
• Predictive Value of Tests
• Prognosis
• Prospective Studies
• Purinergic P2Y Receptor Antagonists (administration & dosage)
• Risk Factors
• Ticagrelor
• Ticlopidine (administration & dosage, analogs & derivatives)
• Troponin T (blood)