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For Jim*, peripheral revascularization helped to ease claudication stemming from peripheral artery disease (PAD). However, this was his second revascularization procedure, and Jim fears that he may need another, or even face amputation in the future.
Is there anything that can be done to protect Jim from these feared consequences of PAD?
Even after revascularization, patients with PAD remain at high risk of cardiovascular and limb events , with the risk rising from approximately 1 in 6 patients after 1 year to approximately 1 in 3 patients after 4.5 years.1 For patients who experience major adverse limb events (MALE) after revascularization, the consequences are especially concerning, because these patients are approximately 8 times more likely to need another revascularization or a limb amputation, highlighting the need to prevent post-revascularization MALE.2
To reduce the risk of cardiovascular and limb events after revascularization, patients are often prescribed intensified antithrombotic therapy, such as dual antiplatelet therapy (DAPT). 3,4 However, the guideline recommendations are largely extrapolated from data in the coronary revascularization setting, and evidence on the benefit of intensified antithrombotic therapy after peripheral revascularization is scarce.3,5-7 Previous trials in patients with symptomatic PAD following peripheral revascularization treated with either a vitamin K antagonist or DAPT showed no clinical benefit in graft occlusion, revascularization, above-ankle amputation, death or severe bleeding compared with antiplatelet therapy alone.8,9 However, adjudicated major bleeding complications were increased in those treated with a vitamin K antagonist compared with aspirin.9 These findings highlighted the need for adequately powered randomized trials of antithrombotic treatment in a primary PAD population following revascularization with adjudicated major adverse cardiovascular events, MALE and bleeding endpoints.3
The first trial to demonstrate significant protection from major adverse vascular events in patients with PAD following recent revascularization was VOYAGER PAD (N=6564).10 In this trial, dual pathway inhibition (DPI) with rivaroxaban vascular dose 2.5 mg twice daily (bid) plus aspirin 100 mg once daily (od) versus aspirin 100 mg od showed a 15% reduction (HR 0.85; 95% CI 0.76–0.96; p=0.009) in the composite primary efficacy endpoint of acute limb ischaemia, major amputation of vascular aetiology, myocardial infarction, ischaemic stroke or cardiovascular death.10 Furthermore, the primary safety outcome of TIMI (Thrombolysis In Myocardial Infarction) major bleeding was not significantly different with DPI versus aspirin (HR 1.43; 95% CI 0.97–2.10; p=0.07).10 These results suggest protection with DPI against thrombotic events in multiple vascular beds, with manageable bleeding events.
Reassuringly, there were also reductions in secondary limb outcomes with DPI versus aspirin, including a 12% reduction in unplanned revascularization of the index leg for recurrent ischaemia (hazard ratio [HR]=0.88; 95% confidence interval [CI] 0.79–0.99; p=0.03).10 Furthermore, hospitalization for coronary or peripheral event of a thrombotic nature was reduced by 28% (HR=0.72; 95% CI 0.62–0.85; p<0.001) with DPI compared with aspirin.10 Therefore, DPI shows promise not only in reducing major adverse vascular events, but also in protecting patients from the burden of repeat procedures and return to hospital.
DPI reduced the risks of repeat revascularization and hospitalization10
bid, twice daily; CI, confidence interval; DPI, dual pathway inhibition; HR, hazard ratio; od, once daily
As vascular surgeon Professor Sebastian Debus explains in this video, ‘[Rivaroxaban 2.5 mg bid plus aspirin 100 mg od] now has a severe benefit for all our PAD patients since the risk of redo surgery, rehospitalization, reduced overall lifetime and the risk of acute limb events and cardiac events is markedly reduced.’
The results of VOYAGER PAD led to specific recommendation updates to the European label of rivaroxaban 2.5 mg bid plus low-dose aspirin for the prevention of atherothrombotic events in patients with symptomatic PAD at high risk of ischaemic events, including those with a recent lower-extremity revascularization.11
Recent European label update builds confidence in DPI for patients with symptomatic PAD at high risk of ischemic events following a recent lower-extremity revascularization11
DAPT, dual antiplatelet therapy; DPI, dual pathway inhibition; PAD, peripheral artery disease; TIA, transient ischaemic attack
The updated European label adds to the recommendations from the 2019 European Society of Vascular Medicine (ESVM) guidelines, the 2019 Global Vascular Guidelines (GVG) and the 2019 European Society of Cardiology (ESC) guidelines on PAD that DPI with rivaroxaban 2.5 mg bid plus low-dose aspirin should be considered in all patients with symptomatic PAD without high risk of bleeding or other contraindications.5-7 The guideline recommendations are based on the results of the COMPASS trial, which investigated DPI in patients with chronic coronary artery disease and/or PAD.12-14 The approval by regulatory authorities and the clinical guidelines build confidence in protecting patients with PAD from major adverse vascular events both in the short- and long-term. As vascular physician Professor Rupert Bauersachs summarizes in this video, ‘Dual pathway inhibition provides a simple and effective management to the vascular physician, of course, to the patient also, covering the immediate and long-term phase, starting right after the revascularization and continuing long term.’
The broadening of the European label for rivaroxaban provides guidance on the use of DPI in patients with symptomatic PAD following peripheral revascularization, and provides reassurance that you have an effective treatment option to reduce the risk of major adverse vascular events, including repeat revascularizations and hospitalizations, in patients like Jim.