Original Title: Acute Limb Ischemia and Outcomes With Vorapaxar in Patients with Peripheral Artery Disease: Results From TRA2°P-TIMI 50. Reference: Marc P. Bonaca et al. Circulation. 2016 Mar 8;133(10):997-1005.

Patients with peripheral artery disease have a high risk of acute limb ischemia, an event that may result in the loss of the affected limb.

This study addresses the causes, sequelae and predictors of acute limb ischemia and test the hypothesis that PAR-1 antagonism with vorapaxar reduce its incidence.

The TRA2°P-TIMI 50 was a randomized, double blind, placebo controlled trial that tested Vorapaxar in stable patients, including 3787 with a history of symptomatic peripheral arterial disease. Acute limb ischemia was pre-specified in the study.

A total of 150 acute limb ischemia events in 108 patients occurred during follow up(3.9% to 3 years, 1.3% annualized).

In patients with symptomatic peripheral artery disease, smoking, prior revascularization and ankle-brachial index were predictors of acute limb ischemia.

Most of the acute ischemia events were due to femoropopliteal surgical graft thrombosis (56%), followed by native vessel in situ thrombosis (27%).

Stent thrombosis and thromboembolism caused acute limb ischemia in 13% and 5% respectively. Amputation occurred in 17.6% of acute limb ischemia patients. Vorapaxar reduced the chance of acute ischemia by 41% (HR 0.58, 95% CI 0.39 to 0.86; p=0.006) and this efficacy was consistent across acute ischemia etiology.

Conclusion
In selected patients with symptomatic peripheral artery disease with no atrial fibrillation, the rate of acute limb ischemia is 1.3% per year and is more often caused by acute thrombosis of a surgical bypass graft and in situ thrombosis. Vorapaxar reduces acute limb ischemia across all etiologies.