An effective antithrombotic treatment strategy for patients who have undergone lower-extremity revascularization due to PAD is under investigation to reduce the risk of major vascular ischemic events.
On March 28, 2020 in the "NEJM" was published the results of the VOYAGER PAD trial, which purpose was to study the efficacy and safety of rivaroxaban 2.5 mg twice daily added to standard of care treatment in patients with symptomatic PAD, who recently undergone (within the last 10 days prior to randomization) technically successful lower-extremity revascularization.
After a median 3-year follow up (n=6564, median age 67 years, 26% women, CHD – 30%, DM - 40%, eGFR<60 ml/min/1.73m2 - 20%, aspirin – 99.1%, clopidogrel up to 6 months at the discretion of the investigator – 50.5%, endovascular or hybrid revascularization – 65%, surgical revascularization – 35%) in the rivaroxaban/aspirin group the incidence of the primary composite efficacy outcome (acute limb ischemia, major amputation for vascular causes, myocardial infarction, ischemic stroke or death from cardiovascular causes) was significantly lower compared with placebo/aspirin group (17.3% vs. 19.9%, respectively) with a reduce in relative risk by approximately 15% (HR 0.85; 95%CI, 0.76-0.96; p=0.009) mainly by reducing acute limb ischemia rates. In the rivaroxaban/aspirin group there was a tendency to increase in the incidence of TIMI major bleeding (2.65% vs. 1.87% in the placebo/aspirin group) with an increase in relative risk by 43% (HR 1.43; 95%CI, 0.97-2.10; p=0.07). In the secondary analysis using ISTH scale, the incidence of major bleeding between groups was statistically significant (5.94% vs. 4.06%, respectively) with a similar increase risk by 42% (HR 1.42; 95% CI, 1.10-1.84; p=0.007). Estimate that for every 10,000 patients who were treated with rivaroxaban for 1 year at a dose of 2.5 mg twice daily in addition to aspirin were prevented 6 times more ischemic events relative to bleeding events. It should be noted that the incidence of intracranial or fatal bleeding did not differ between groups. Secondary analysis did not confirm the effect of additional clopidogrel treatment on the studied primary end points.
Thus, in the VOYAGER PAD study the combination of rivaroxaban with aspirin was effective and safe in reducing the risk of major ischemic events in patients with symptomatic peripheral artery disease who had recently undergone lower-extremity revascularization.
References:
1) Bonaca MP, Bauersachs RM, Anand SS, et al. Rivaroxaban in Peripheral Artery Disease After Revascularization. N Engl J Med 2020;Mar 28
2) VOYAGER-PAD: Rivaroxaban Associated With Reduced Adverse Limb, CV Events in PAD Patients. https://www.acc.org/latest-in-cardiology/articles/2020/03/24/16/41/sat-9am-voyager-pad-rivaroxaban-prevention-cv-acc-2020
