Editor's Choice – External Applicability of the COMPASS and VOYAGER-PAD Trials on Patients with Symptomatic Lower Extremity Artery Disease in France: The COPART Registry

Abstract

WHAT THIS PAPER ADDS Only 30.1% of patients hospitalised for symptomatic lower extremity artery disease are eligible for rivaroxaban 2.5 mg twice daily plus aspirin, based on the COMPASS or VOYAGER-PAD criteria. These patients have higher rates of ischaemic events than those in these trials. The one year cumulative incidences were 6.0% (95% confidence interval [CI] 4.3 e 8.1) in the COMPASS eligible subset vs. 3.5% (95% CI 2.9 e 4.3) in the COMPASS control arm for major adverse cardiovascular events, and 27.9% (95% CI 19.9 e 38.3) in the VOYAGER-PAD eligible subset vs. 6.0% (95% CI 5.3 e 6.9) in the VOYAGER-PAD control arm for major adverse limb events. This regimen may have greater benefits in the real world population.Objective: The aim of this study was to examine the external applicability of the COMPASS and the VOYAGER-PAD trials in patients with lower extremity artery disease (LEAD) in the real world. Methods: This was a multicentre retrospective analysis of prospectively collected COPART data, a French multicentre registry of patients hospitalised for symptomatic LEAD. The proportion of patients eligible for the combination of rivaroxaban 2.5 mg twice daily plus aspirin based on either COMPASS or VOYAGER-PAD criteria is reported. The one year cumulative incidence of outcomes between eligible and non-eligible patients, as well as eligible patients vs. control arms of the COMPASS (LEAD patient subgroup) and the VOYAGER-PAD trials were compared. Analyses were performed using Cox models. Results: Of 2 259 evaluable patients, only 679 (30.1%) were eligible for a low dose rivaroxaban plus aspirin regimen. Others were not eligible because of the need for anticoagulant (48.5% and 38.9% of patients meeting COMPASS and VOYAGER-PAD exclusion criteria, respectively) or dual antiplatelet therapy use (15.7% and 16.5%, respectively), high bleeding risk (14.4% and 11.6%, respectively), malignancy (26.1% and 21.0%, respectively), history of ischaemic/haemorrhagic stroke (21.1% and 19.8%, respectively), and severe renal failure (13.2% and 10.5%, respectively). COMPASS and VOYAGER-PAD eligible and ineligible patients were at higher risk of ischaemic events than participants in these trials. The one year cumulative incidences were 6.0% (95% CI 4.3 e 8.1) in the COMPASS eligible subset vs. 3.5% (95% CI 2.9 e 4.3) in the COMPASS control arm for major adverse cardiovascular events, and 27.9% (95% CI 19.9 e 38.3) in the VOYAGER-PAD eligible subset vs. 6.0% (95% CI 5.3 e 6.9) in the VOYAGER-PAD control arm for major adverse limb events.

New Horizons in Peripheral Artery Disease

“…Network meta-analysis of individuals with PAD from CAPRIE and COMPASS demonstrated no superiority of rivaroxaban and aspirin over clopidogrel [ 39 ]. Furthermore, both COMPASS and VOYAGER excluded patients with significant multi-morbidity and those considered at high risk of bleeding and, based on registry data, only 30% of patients hospitalised with symptomatic PAD would have been eligible for inclusion [ 40 ].…”

“…Furthermore, many patients with symptomatic PAD also have indications for long-term anticoagulation (e.g. those with atrial fibrillation) in whom the added benefit of antiplatelet therapy is unknown and is likely to significantly increase bleeding risk [ 40 ].…”

Applying Randomised Trials to the Real World: A VOYAGER of Discovery

“…Lapébie et al reported on the external applicability of both COMPASS and VOYAGER to patients in the French COPART registry, finding that only 30.1% of patients would have been eligible for inclusion in either trial. 4 In this issue of the Journal, Søgaard et al present a similar analysis of patients in the Danish Vascular Registry, finding 27.1% of patients would have been eligible. 5 Both studies found that patients in the registries (both eligible and ineligible for the trials) were at higher risk of major ischaemic events than those in the control arms of the trials, making it conceivable that dual pathway inhibition might be even more beneficial than the results of the trials would suggest.…”

“…Trial subgroup analysis and 'real world' application of trial results shine a harsh spotlight on these issues. 4,5 The allimportant risk balance is then debated extensively by clinicians trying to do the right thing for an individual patient.…”

Navigating the Passage for Better Understanding and Prognosis for Acute Limb Ischemia After Lower-Extremity Revascularization

“…Recently, 2 studies based on French and Danish registry data have provided data on the external applicability of VOYAGER-PAD to patients encountered in routine clinical practice. 9,10 In both studies, fewer than one-third of patients who underwent revascularization in routine practice would have been eligible in the VOYAGER-PAD trial. Compared with participants enrolled in VOYAGER-PAD, patients in routine care were older and had more severe PAD, higher bleeding risk, and generally poorer prognosis.…”