Ongoing trials examine optimal antithrombotic therapy, endovascular treatment vs. surgery
CHICAGO —The BEST-CLI and VOYAGER-PAD trials will offer insight into the best treatment strategies for patients with peripheral artery disease, two experts said during a session at AMP: The Amputation Prevention Symposium.
“Critical limb ischemia affects a significant minority of patients with PAD,” R. Kevin Rogers, MD, MSc, associate professor and director of vascular medicine and intervention at the University of Colorado, said during his presentation. “Most treatments are aimed at improving limb health, but without timely revascularization, amputation rates can approach 40% with a year.”
To overcome limitations of studies investigating optimal revascularization strategies, researchers designed BEST-CLI: a prospective, randomized, pragmatic, multicenter, open-label clinical trial that will enroll 2,100 patients with CLI and infrainguinal PAD who are candidates for both surgery and endovascular therapy at 140 sites throughout the United States and Canada.
Patients are stratified at the time of randomization based on ischemic rest pain vs. tissue loss, and 2-year follow-up is planned for each patient. The operator will determine the best treatment, which includes all endovascular strategies and surgical bypass techniques.
Unlike previous studies, the primary outcome is major adverse limb event-free survival, defined as above-ankle amputation or major reintervention. Secondary endpoints include reintervention and amputation-free survival, amputation-free survival and major adverse limb event-free postoperative death within 30 days of the index procedure. Secondary clinical endpoints, quality of life and functional outcomes are also being assessed.
Rogers said the researchers are emphasizing the need for multidisciplinary involvement from all physicians treating CLI, including vascular surgeons, interventional radiologists and interventional cardiologists.
Currently, 138 sites are activated, 11 sites are closed, 125 are open for enrollment and 19 sites are in start-up. The first patient was randomly assigned to treatment in August 2014, and as of April 2017, 950 patients have been randomly assigned. Nearly 78% of sites are multidisciplinary, with the breakdown favoring vascular surgery.
Enrollment has been slow, according to Rogers, so the researchers have made protocol amendments. Patients with common femoral artery stenosis or occlusion are allowed as long as there is sufficient distal disease to cause CLI. If a patient has significant common femoral artery disease, thromboendarterectomy or endovascular therapy can be used. These treatments can be done before or at the same time as index revascularization of the more distal-occlusive disease and is chosen irrespective of the randomized treatment for the more distal-occlusive disease.
Additionally, if a patient has greater than 70% common femoral artery stenosis, greater than 70% profunda femoris artery stenosis or occlusion of either artery, those arteries must be treated before randomization for more distal disease. After treatment, patients may be eligible if they still have symptoms of rest pain or continues to meet the definition of CLI on repeat hemodynamic assessment.
Currently, questions also persist about the optimal antithrombotic management of patients with PAD undergoing revascularization, Jihad A. Mustapha, MD, FACC, FSCAI, director of cardiovascular research at Metro Health – University of Michigan Health in Wyoming, Michigan, said during his presentation. Moreover, data on dual antiplatelet therapy after endovascular interventions or surgical revascularization are unclear.
Rivaroxaban (Xarelto, Janssen), however, has shown promise in treating ACS. Consequently, researchers designed the VOYAGER PAD trial to evaluate its safety and efficacy in reducing thrombotic vascular events in patients with PAD undergoing revascularization.
Approximately 6,500 patients undergoing peripheral revascularization will be assigned to twice-daily rivaroxaban 2.5 mg and once-daily aspirin 100 mg or aspirin alone. The primary efficacy endpoint is a composite of MI, stroke or CV death, acute limb ischemia and major amputation due to vascular etiology, and the primary safety endpoint is TIMI major bleeding events.
Patients aged 50 years or older with symptomatic and hemodynamic PAD and technically successful peripheral revascularization within 7 days before randomization qualify for study inclusion.
There are three study cohorts: patients undergoing surgery, patients undergoing endovascular therapy with clopidogrel and patients undergoing endovascular therapy without clopidogrel.
The study is event-driven (approximately 1,105 endpoint events), according to Mustapha. Enrollment began in 2015 and is ongoing.
“This trial is going after a truly unmet need,” Mustapha said. “PAD remains a frequent and serious disorder with a high rate of severe thrombotic complications. VOYAGER PAD is the largest antithrombotic trial performed in patients with PAD undergoing revascularization and will provide important long-term and large-scale outcome data in patients undergoing revascularization for PAD.” – by Melissa Foster
Mustapha JA. Session 1: CLI in 2017.
Rogers RK. Session 1: CLI in 2017. Both presented at: AMP: The Amputation Symposium; Aug. 9-12, 2017; Chicago.
Disclosures: Mustapha reports consulting for Abbott Vascular, Bard Peripheral Vascular, Boston Scientific, Cardiovascular Systems Inc., Medtronic, Spectranetics and Terumo Medical. Rogers reports no relevant financial disclosures.