Patients with symptomatic peripheral artery disease who took rivaroxaban (Xarelto, Bayer) saw a 15% reduction in the risk of major adverse limb and cardiovascular events.
When combined with aspirin following a procedure to treat blocked arteries in the leg, patients with symptomatic peripheral artery disease (PAD) who took rivaroxaban (Xarelto, Janssen) saw a 15% reduction in the risk of major adverse limb and cardiovascular events compared with those receiving aspirin alone.
The researchers also found that although patients taking rivaroxaban had higher rates of bleeding, there was no excess in severe bleeding events, which is a common concern when using anticoagulants.
PAD affects an estimated 10 million adults in the United States and 200 million people worldwide. The disease is associated with leg pain, difficulty walking, and poor circulation, which can lead to non-healing wounds and a high rate of limb loss. Serious adverse events are a serious concern for patients with PAD, including acute limb ischemia, which can lead to limb amputation or death.
The international Voyager PAD trial has the goal of evaluating whether rivaroxaban combined with aspirin is better than aspirin alone in reducing these events in some PAD patients. There have been few studies evaluating symptomatic patients undergoing lower limb revascularization, according to the study authors. Notably, there are no Class I recommendations for antithrombotic therapy beyond aspirin or clopidogrel, and no recommendations specific to the post-revascularization setting for patients with PAD.
The trial enrolled 6564 patients at 542 medical centers in 34 countries, who were then randomly assigned in a double-blind, 1-to-1 fashion to receive either rivaroxaban 2.5 mg twice daily and aspirin 100 mg daily or placebo and aspirin 100 mg daily for a median of 28 months. A limited course of clopidogrel was allowed at the discretion of the physician. The average age was 64, and 74% were male.
Of the 6564 patients, approximately 25% needed lower limb revascularization due to critical limb ischemia, whereas 75% of those reported claudication and symptoms of leg pain. Approximately two-thirds of the patients underwent endovascular revascularization treatment with stenting and balloons, and one-third had surgery to bypass the blockage.
At 28 months median follow-up, the patients who received rivaroxaban plus aspirin had a significant reduction in the composite primary endpoint of acute limb ischemia, major amputation for vascular cause, heart attack, ischemic stroke, or cardiovascular death compared with those receiving aspirin alone. The event rates were 17.3% and 19.9%, respectively.
The principal safety outcome was thrombolysis in myocardial infarction major bleeding, and although these bleeds were more frequent in patients receiving rivaroxaban plus aspirin (2.7%, compared with 1.9% in those receiving aspirin alone), the researchers reported that this difference was not statistically significant. They found no difference in intracranial bleeds or fatal bleeding.
The efficacy and safety results were consistent across all major subgroups, including those with critical limb ischemia and regardless of the type of revascularization or surgery received.
“These data provide evidence of an antithrombotic regimen that effectively reduces risk, and although bleeding rates were higher, the overall risk-benefit remains quite favorable and could have a profound impact on patients’ lives,” said Marc Bonaca, MD, lead author of the study, in a statement.
Rivaroxaban reduces risk in symptomatic PAD post-intervention [news release]. EurekAlert!; March 31, 2020. https://www.eurekalert.org/pub_releases/2020-03/acoc-rrr032820.php. Accessed March 31, 2020.