After patients with peripheral artery disease undergo lower-extremity revascularization, they are at high risk for major adverse limb events, and new findings from a prespecified analysis of data from the VOYAGER-PAD trial show that treatment with the direct-acting oral anticoagulant rivaroxaban along with aspirin significantly cut the rate of total major adverse limb events in these patients.
These findings confirm the drop in first major adverse limb events linked to rivaroxaban treatment that was VOYAGER-PAD’s primary result, reported just over a year ago.
The new total-event analysis also provides important insight into the huge magnitude of total major adverse limb events that patients with PAD can develop following lower-extremity revascularization (LER).
The 6,564 patients who all received aspirin and were randomized to either rivaroxaban (Xarelto) or placebo had 4,714 total events during a median follow-up of 2.5 years following their revascularization procedure. This included 1,092 first primary events (a composite of acute limb ischemia, major amputation for vascular causes, MI, ischemic stroke, or cardiovascular death), 522 primary events that occurred as second or subsequent events among patients after a first primary event (a nearly 50% increase from first events only), and 3,100 additional vascular events that did not fit into the primary-event category, most often a peripheral revascularization procedure, Rupert M. Bauersachs, MD, said at the annual scientific sessions of the American College of Cardiology.
“We were all astonished by this high event rate,” Dr. Bauersachs said during his report.
The total-event analysis that he reported showed that treatment with rivaroxaban resulted in a significant 14% relative reduction, compared with placebo in the incidence of total primary events, which closely tracks the significant 15% relative reduction in first primary events reported from the VOYAGER-PAD trial in 2020. Treatment with rivaroxaban also significantly linked with a 14% cut in total vascular events, compared with placebo, including the many events not included in the primary endpoint, said Dr. Bauersachs, who until his retirement in May 2021 was director of the Clinic for Vascular Medicine at the Darmstadt (Germany) Clinic. Concurrently with the report, the results appeared online.
“If one focuses only on first events, you miss the totality of disease burden. There is even greater benefit by reducing total events,” Dr. Bauersachs said during a press briefing. Adding rivaroxaban prevented roughly 2.6 first primary events for every 100 patients treated, but it also prevented 4.4 total primary events and 12.5 total vascular events for every 100 treated patients.
An ‘incredibly high’ event rate
“I don’t think any of us imagined the level of morbidity in this population. The event rate is incredibly high,” commented Joshua A. Beckman, MD, professor and director of vascular medicine at Vanderbilt University Medical Center, Nashville, Tenn.
Because treatment with rivaroxaban showed clear efficacy for also preventing subsequent events it should not be considered to have failed in patients who have a vascular event while on rivaroxaban treatment, he added as designated discussant for the report. Treatment with rivaroxaban “should be continued indefinitely,” he concluded.
“It’s quite astonishing to see the magnitude of [total] events in these patients,” commented Sahil A. Parikh, MD, a cardiologist and director of endovascular services at Columbia University Medical Center in New York. “We’ve always known that these are high-risk patients, but exactly how high their risk is was not well understood until these data came to light.”
Dr. Parikh also noted that, despite the clear evidence reported from VOYAGER-PAD more than a year ago proving the efficacy and safety of adding rivaroxaban to aspirin for long-term treatment of patients with PAD following LER, this regimen has not yet become standard U.S. practice.