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Vorapaxar reduces acute limb ischemia in patients with PAD
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Use of vorapaxar, a PAR-1 antagonist, was associated with reduced acute limb ischemia in patients with symptomatic peripheral artery disease. This finding was consistent across all etiology, including in situ thrombosis and surgical graft thrombosis, according to new data from the TRA 2P-TIMI 50 trial.
The randomized, double blind, placebo-controlled trial of vorapaxar (Zontivity, Merck) enrolled 26,449 patients with stable atherosclerosis, including 3,787 patients with symptomatic PAD.
The current analysis, conducted by Marc P. Bonaca, MD, MPH, investigator for the TIMI Study Group and associate physician at Brigham and Women’s Hospital and Harvard Medical School, and colleagues focused on the causes, treatments and outcomes of acute limb ischemia, and whether the positive outcomes associated with vorapaxar were consistent across etiology.
Marc P. Bonaca
The patients with PAD were randomly assigned vorapaxar sulfate 2.5 mg daily or matching placebo. Median follow-up was 2.5 years.
According to the findings, 150 acute limb ischemia events occurred in 108 patients; 56% of these events were due to surgical graft thrombosis and 27% due to native vessel in situ thrombosis. Stent thrombosis and thromboembolism were less frequent causes. Current smoking, a very low ankle-brachial index ( 0.5) or high ankle-brachial index ( 1.3), and a history of peripheral revascularization were predictors of acute limb ischemia (P = .082).
All patients with acute limb ischemia required hospitalization, and 60% underwent surgical treatment, including 16% who required amputation, and 31% who needed a new surgical bypass. Endovascular therapy with or without thrombolysis was performed in 28% of the patients; 7% of patients only received thrombolysis. Four patients (3.7%) died during hospitalization, and by discharge 14.8% of patients had died or required extended care outside of the home.
Vorapaxar reduced first acute limb ischemia events by 42% (HR = 0.58; 95% CI, 0.39-0.86) and all acute limb ischemia events by 41% (94 events vs. 56 events; RR = 0.59; 95% CI, 0.38-0.93). The reduction of acute limb ischemia was observed across etiology.
According to Bonaca and colleagues, the results showed that acute limb ischemia events occur at a frequency similar to stroke and MI in patients with symptomatic PAD and that those events can be reduced with vorapaxar, regardless of etiology.
“Findings with respect to graft thrombosis are particularly interesting in that prior trials of thienopyridines and anticoagulants have not shown consistent benefit for graft patency in trials after bypass,” the researchers wrote. “The efficacy of vorapaxar in contrast to generally neutral findings with anticoagulants raises the question of whether the benefit is purely an antithrombotic effect or whether there are additional actions on the vascular endothelium.” – by Tracey Romero
Disclosure: The TRA 2P-TIMI 50 trial was funded by a grant from Merck, with grant support from Accumetrics, Amgen, AstraZeneca, Beckman Coulter, Bristol-Myers Squibb, CV Therapeutics, Daiichi Sankyo, Eli Lilly, GlaxoSmithKline, Integrated Therapeutics, Nanosphere, Novartis Pharmaceuticals, Nuvelo, Ortho-Clinical Diagnostics, Pfizer, Roche Diagnostics, Sanofi-Aventis, Sanofi-Synthelabo, Siemens Medical Solutions and Singulex. Bonaca reports receiving support from an NHLBI research career development award and consultant fees from AstraZeneca, Bayer, Merck and Roche Diagnostics. Please see the full study for a list of all other researchers’ relevant financial disclosures.
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