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

Study Questions:

What is the prognostic importance of high-sensitivity troponin T (hs-TnT), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and growth differentiation factor-15 (GDF-15) in relation to randomized treatment (ticagrelor vs. clopidogrel) and management strategy (with or without revascularization) in the non-ST-segment elevation acute coronary syndrome (NSTE-ACS) subgroup of the PLATO trial?

Methods:

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. The treatment effects in relation to the levels of the biomarkers were evaluated with a Cox proportional hazards model within the respectively in-hospital invasive and noninvasive treatment groups.

Results:

Increasing levels of hs-TnT were associated with increasing risk of cardiovascular (CV) death, myocardial infarction (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 versus 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 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:

The authors concluded that hs-TnT, NT-proBNP, and GDF-15 are predictors of CV death, MI, and stroke in patients with NSTE-ACS managed noninvasively, and NT-proBNP and GDF-15 also in those managed invasively.

Perspective:

This study reported that NT-proBNP and GDF-15 were strong predictors of subsequent CV death and spontaneous MI, regardless of in-hospital revascularization procedures. In addition, patients with higher levels of NT-proBNP or GDF-15 had larger absolute benefits from ticagrelor, due to their association with higher risks of subsequent events, and lack of interaction with treatment effect. Elevated hs-TnT predicted substantial benefit of ticagrelor over clopidogrel both in invasively and noninvasively managed patients, while no apparent benefit was seen at normal hs-TnT. These biomarkers may help to individualize treatment with potent P2Y12 inhibitors in NSTE-ACS, e.g., by selecting more intense treatment for troponin-positive patients at intermediate to high risk, regardless of invasive management strategy, and down-prioritizing its use in noninvasively managed patients with normal hs-TnT levels.

Clinical Topics: Acute Coronary Syndromes, Invasive Cardiovascular Angiography and Intervention, ACS and Cardiac Biomarkers, Interventions and ACS

Keywords: Myocardial Infarction, Stroke, Acute Coronary Syndrome, Follow-Up Studies, Platelet Aggregation Inhibitors, Ticlopidine, Blood Platelets, Angioplasty, Balloon, Coronary, Purinergic P2Y Receptor Antagonists, Proportional Hazards Models, Biological Markers, Growth Differentiation Factor 15, Organoplatinum Compounds, Natriuretic Peptide, Brain, Troponin


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