Atherothrombotic Risk and Vorapaxar in Prior MI

Study Questions:

What are the readily available clinical characteristics that are associated with long-term atherothrombotic risk and might distinguish a population of patients with established ischemic heart disease in whom the benefit of intensive therapy most clearly outweighs risk?


The investigators identified independent clinical indicators of atherothrombotic risk among 8,598 stable, placebo-treated patients with a prior myocardial infarction (MI) followed for 2.5 years (median) in the TRA 2°P-TIMI 50 trial. The efficacy and safety of vorapaxar was assessed by baseline risk among patients with prior MI without prior stroke or transient ischemic attack (TIA) for whom there was a clinical indication for vorapaxar. Endpoints were cardiovascular (CV) death, MI, or ischemic stroke (CVD/MI/iCVA) and GUSTO severe bleeding.


The nine independent risk predictors were age, diabetes, hypertension, smoking, peripheral arterial disease, prior stroke, prior coronary bypass grafting (CABG), heart failure, and renal dysfunction. A simple integer-based scheme using these predictors showed a strong graded relationship with the rate of CVD/MI/iCVA and the individual components (p-trend < 0.001 for all). High-risk patients (≥3 risk indicators; 20% of population) had a 3.2% absolute risk reduction (ARR) in CVD/MI/iCVA with vorapaxar and intermediate-risk (1-2; 61%) had a 2.1% ARR (p < 0.001 each), translating to a number-needed-to-treat of 31 and 48. Bleeding increased across risk groups (p-trend < 0.01); however, net clinical outcome was increasingly favorable with vorapaxar across risk groups. Fatal bleeding or intracranial hemorrhage was 0.9% with both treatments in high-risk patients.


The authors concluded that stratification of baseline atherothrombotic risk can assist with therapeutic decision making regarding vorapaxar use for secondary prevention after MI.


This study reports that nine routinely assessed clinical characteristics (age, diabetes, hypertension, smoking, peripheral arterial disease, prior stroke, prior CABG, history of heart failure, and renal dysfunction) established not only a gradient of risk for recurrent ischemic events, but also distinguished a pattern of increasing absolute benefit from treatment with vorapaxar. This approach may outline a strategy that could be used by clinicians to assist with risk stratification and therapeutic decision making regarding vorapaxar use for secondary prevention after MI. It should be noted that these data are derived from a population of patients who were identified for and agreed to participate in a clinical trial, and thus, unaccounted selection biases may influence the generalizability to the general population, and additional verification is needed.

Clinical Topics: Acute Coronary Syndromes, Anticoagulation Management, Heart Failure and Cardiomyopathies, Prevention, Vascular Medicine, Atherosclerotic Disease (CAD/PAD), Anticoagulation Management and ACS, Acute Heart Failure, Hypertension, Smoking

Keywords: Acute Coronary Syndrome, Anticoagulants, Atherosclerosis, Diabetes Mellitus, Heart Failure, Hypertension, Intracranial Hemorrhages, Ischemic Attack, Transient, Myocardial Infarction, Myocardial Ischemia, Peripheral Arterial Disease, Risk, Secondary Prevention, Smoking, Stroke

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