Acute Limb Ischemia and Outcomes With Vorapaxar in Patients with Peripheral Artery Disease: Results From TRA2°P-TIMI 50
Background—Patients with peripheral artery disease (PAD), are at heightened risk of acute limb ischemia (ALI), a morbid event that may result in limb loss. We investigated the causes, sequelae and predictors of ALI in a contemporary population with symptomatic PAD and whether PAR-1 antagonism with vorapaxar reduced ALI overall and by etiology.
Methods and Results—TRA2°P-TIMI 50 was a randomized, double-blind, placebo controlled trial of vorapaxar in stable patients including 3,787 with symptomatic PAD. ALI was a prespecified adjudicated endpoint using a formal definition. A total of 150 ALI events occurred in 108 patients during follow-up (placebo 3-yr-rate 3.9%, 1.3% annualized). For patients with symptomatic PAD, prior peripheral revascularization, smoking, and ABI were predictive of ALI. The majority of ALI events occurred due to surgical graft thrombosis (56%), followed by native vessel in situ thrombosis (27%). Stent thrombosis and thromboembolism caused ALI in 13% and 5% respectively. Amputation occurred in 17.6% presenting with ALI. Vorapaxar reduced first ALI events by 41% (HR 0.58, 95%CI 0.39-0.86,p=0.006), as well as total ALI events by 41% (94 events vs. 56 events, risk ratio 0.59, 95% CI 0.38-0.93,p=0.022). The efficacy of vorapaxar was consistent across etiology of ALI.
Conclusions—In selected patients with symptomatic PAD and without atrial fibrillation, ALI occurs at a rate of 1.3% per year, is most frequently caused by acute bypass graft thrombosis or in situ thrombosis of a diseased vessel, and often results in limb loss. Vorapaxar reduces ALI in patients with symptomatic PAD with consistency across etiology including surgical graft thrombosis and in-situ thrombosis.
Clinical Trial Registration Information—www.clinicaltrials.gov. Identifier: NCT00526474.
- acute limb ischemia
- peripheral artery disease
- peripheral vascular disease
- Received September 4, 2015.
- Revision received January 14, 2016.
- Accepted January 22, 2016.