Vorapaxar reduces peripheral revascularization in patients with PAD
Among patients with peripheral artery disease, the use of vorapaxar appears to reduce peripheral revascularization in a manner that is directionally consistent across procedure type and indication, according to recent findings.
In the substudy of the TRA2 P-TIMI 50 trial, researchers randomly assigned 26,449 patients with stable atherosclerotic vascular disease, including the following: CAD (recent MI), cerebrovascular disease (recent stroke) and symptomatic PAD. Eligible patients with PAD had a history of intermittent claudication and an ankle-brachial index less than 0.85 or previous revascularization for limb ischemia.
The primary population for the current analysis was composed of patients with known PAD history at randomization (n = 5,845), independent of qualifying diagnosis. Eligible patients were randomly assigned at a 1:1 ratio to treatment with vorapaxar sulfate (Zontivity, Merck/Aralez) 2.5 mg per day or matching placebo, and were grouped by qualifying disease state and intention to prescribe a thienopyridine.
The study’s prespecified limb efficacy endpoints included acute limb ischemia, peripheral revascularization, amputation for vascular reasons and urgent hospitalization for vascular cause of ischemic origin.
Marc P. Bonaca, MD, M PH, from the TIMI Study Group, cardiovascular division, department of medicine, Brigham and Women’s Hospital and Harvard Medical School, and colleagues found that during a median 2.5 years of follow-up, 1,518 peripheral revascularization procedures occurred in 934 patients (16%).
In more than half of the peripheral revascularizations performed, the indication was for worsening claudication (n = 838; 55%). The remainder were for critical limb ischemia (n = 370; 24%) and acute limb ischemia (n = 242; 16%). In 68 patients (4%), revascularization was performed for severe stenosis detected during monitoring for prior graft or stent placement.
Overall, vorapaxar significantly reduced peripheral revascularization by 18% at 3 years (19.3% in placebo, 15.4% for vorapaxar; HR = 0.82; 95% CI, 0.72-0.93). An analysis of all peripheral revascularizations, including repeat procedures, found a consistently significant decrease with vorapaxar (n = 671 for vorapaxar vs. n = 847 for placebo; HR = 0.8; 95% CI, 0.69-0.92). During follow-up, 934 patients had first major adverse limb events; 790 of these patients were on study treatment at the time of the procedure.
In a related editorial, Robert D. Safian, MD, of the Center for Innovation and Research in Cardiovascular Diseases, Beaumont Health, Royal Oak, Michigan, noted that this study is limited by its focus on directional consistency.
The main limitation of this study is that the authors have obscured these findings by emphasizing the directional consistency of their results, in the absence of significant differences,” Safian wrote. “Nevertheless, there seem to be consistencies among the three published PAD substudies of TIMI 50, which may have implications for future studies and for appropriate use of vorapaxar.” – by Jennifer Byrne
Disclosure: The study was supported by a grant from Merck. Bonaca reports consulting for AstraZeneca, Bayer and Merck. Please see the full study for a list of the other researchers’ relevant financial disclosures. Safian reports no relevant financial disclosures.