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

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

doi:10.1161/CIRCULATIONAHA.113.004420

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

Circulation. 2014 Jan 21;129(3):293-303. doi: 10.1161/CIRCULATIONAHA.113.004420. Epub 2013 Oct 29.

Authors

Lars Wallentin¹, 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

Affiliation

¹ Department of Medical Sciences, Cardiology and Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden (L.W., D.L., L.W., C.H., S.K.J.); Department of Medical Sciences, Clinical Chemistry and Uppsala Clinical Research Center Uppsala University, Uppsala, Sweden (A.S.); Division of Cardiovascular Health and Disease, Heart, Lung and Vascular Institute, Academic Health Center, Cincinnati, OH (R.C.B.); Department of Medicine, Stanford University, Stanford, CA (R.A.H., K.W.M.); TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Boston, MA (C.P.C.); Department of Cardiology, Medisch Centrum Alkmaar, Alkmaar, Netherlands (J.H.C.); AstraZeneca Research and Development, Mölndal, Sweden (A.H.); Medizinische Klinik, Universitätsklinikum Heidelberg, Heidelberg, Germany (E.G., H.A.K.); Medical Department, Hospital Unit West, Herning/Holstbro, Denmark (S.H.); INSERM-Unité 698, Paris, France; Assistance Publique-Hôpitaux de Paris, Département Hospitalo-Universitaire FIRE, Hôpital Bichat, Paris, France; Université Paris-Diderot, Sorbonne-Paris Cité, Paris, France; NHLI Imperial College, ICMS, Royal Brompton Hospital, London, UK (P.G.S.); and Department of Cardiovascular Science, University of Sheffield, Sheffield, UK (R.F.S.).

PMID: 24170388
DOI: 10.1161/CIRCULATIONAHA.113.004420

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.

Keywords: acute coronary syndrome; biological markers; blood platelets; myocardial infarction; troponin.

Publication types

Comparative Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Acute Coronary Syndrome* / blood
Acute Coronary Syndrome* / drug therapy
Acute Coronary Syndrome* / mortality
Adenosine / administration & dosage
Adenosine / 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
Ticlopidine / analogs & derivatives*
Troponin T / blood

Substances

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

Associated data

ClinicalTrials.gov/NCT00391872