Treatment with vorapaxar was associated with reductions in major adverse cardiovascular events (MACE) and major adverse limb events (MALE) in patients with peripheral artery disease (PAD) and concomitant coronary artery disease (CAD), according to study results published in Vascular Medicine.
In this study, the effects of vorapaxar was examined in 6136 patients with PAD who were enrolled in the TRA 2°P-TIMI 50 trial (ClinicalTrials.gov Identifier: NCT00526474). Study participants were randomly assigned to receive vorapaxar (n=3071) or placebo (n=3065). The primary cardiovascular (CV) efficacy endpoint was MACE, a composite of CV death, myocardial infarction, or stroke.
The occurrence of MALE as a primary limb efficacy outcome, a composite of hospitalization for acute limb ischemia, urgent peripheral revascularization, or major amputation due to limb ischemia, was also assessed. Major bleeding was the primary safety endpoint.
Treatment with vorapaxar was associated with significant reductions in MACE (hazard ratio [HR], 0.85; 95% CI, 0.73-0.99; P =.034) and MALE (HR, 0.70; 95% CI, 0.53-0.92; P =.011) in patients with PAD. Patients with PAD and CAD had a greater absolute risk reduction (ARR) in MACE compared with patients with PAD only (-2.2% vs 0.1%, respectively; number needed to treat [NNT], 45 vs 1000, respectively). The ARR in MALE was higher in patients with prior lower extremity revascularization (2.5% vs 0.2%, respectively; NNT, 40 vs 500, respectively).
Treatment with vorapaxar was associated with an increased risk for major bleeding (HR, 1.39; 95% CI, 1.12-1.71; P =.003). A smaller percentage of patients receiving vorapaxar vs placebo experienced MACE, MALE, or symptomatic bleeding into a critical organ (13.0% vs 15.5%, respectively; HR, 0.82; 95% CI, 0.72-0.94; P =.004).
Study limitations include its exploratory nature, and the inability to generalize those findings to patients with PAD and a history of stroke.
“Among patients with PAD, those with concomitant CAD or prior peripheral revascularization are at an increased risk of thrombotic cardiovascular and limb events, respectively. Because of their elevated risk, these patients may derive more clinical benefit from potent antithrombotic therapies,” noted the study authors.
Disclosure: This clinical trial was supported by Merck. Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.
Qamar A, Morrow DA, Creager MA, et al. Effect of vorapaxar on cardiovascular and limb outcomes in patients with peripheral artery disease with and without coronary artery disease: analysis from the TRA 2°P-TIMI 50 trial [published online January 30, 2020]. Vasc Med. doi: 10.1177/1358863X19892690