Atherothrombotic Risk Stratification and the Efficacy and Safety of Vorapaxar in Patients with Stable Ischemic Heart Disease and Prior Myocardial Infarction
Background—Patients with stable ischemic heart disease and prior MI vary in their risk for recurrent CV events. Atherothrombotic risk assessment may be useful to identify high-risk patients who have the greatest potential for benefit from more intensive secondary preventative therapy such as treatment with vorapaxar.
Methods—We identified independent clinical indicators of atherothrombotic risk among 8,598 stable, placebo-treated patients with a prior MI followed for 2.5 years (median) in TRA 2°P-TIMI 50. The efficacy and safety of vorapaxar was assessed by baseline risk among patients with prior MI without prior stroke or TIA for whom there is a clinical indication for vorapaxar. Endpoints were CV death, MI, or ischemic stroke (CVD/MI/iCVA) and GUSTO severe bleeding.
Results—The 9 independent risk predictors were age, diabetes, hypertension, smoking, peripheral arterial disease, prior stroke, prior coronary bypass-grafting, 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.
Conclusions—Stratification of baseline atherothrombotic risk can assist with therapeutic decision-making regarding vorapaxar use for secondary prevention after MI.
Clinical Trial Registration—http://www.clinicaltrials.gov; NCT00526474.
- Received October 13, 2015.
- Revision received March 25, 2016.
- Accepted April 25, 2016.