New analyses from the VOYAGER PAD clinical trial in both high-risk and fragile patients and those with and without comorbid coronary artery diseases (CAD) were presented at the American Heart Association (AHA) 2023 Scientific Sessions (11–13 November, Philadelphia, USA).
The randomised, double blind VOYAGER PAD trial enrolled more than 6,500 patients in 34 countries who had peripheral arterial disease (PAD) and had undergone lower extremity revascularisation.
Patients were randomly assigned to receive either rivaroxaban (Xarelto, Janssen) or a placebo in addition to daily aspirin. The research team reported in a late-breaking clinical trial presented at ACC.20/WCC that VOYAGER PAD met its primary endpoint, with a 15% statistically significant reduction in the risk of a first major adverse limb or cardiovascular event (MALE or MACE) seen in patients who received rivaroxaban compared with those who received the placebo.
Fragile patients with PAD can be at a heightened risk for MALE, defined as a composite of acute limb ischemia (ALI) and major amputation. In the first of the two analyses presented by Mario Enrico Canonico (University of Colorado Anschutz Medical Campus, Aurora, USA) fragile patients were defined as being older than 75 years, weighing less than 50kg, or having a baseline estimated glomerular filtration rate (eGFR) less than 50 mL/min/1.732.
Rivaroxaban plus aspirin (2.5mg twice daily plus aspirin 100 mg once daily) was shown to be effective in reducing the occurrence of MALE in both fragile and non-fragile patients, compared to aspirin alone. In fragile patients treated with rivaroxaban plus aspirin, 6.2% of patients experienced a MALE compared to 10.3% of patients treated with placebo. In non-fragile patients, 7.9% of patients treated with rivaroxaban plus aspirin experienced a MALE compared to 9.7% of patients treated with placebo.
The second analysis examined the role of rivaroxaban plus aspirin on myocardial infarction (MI) in patients with PAD with and without concomitant coronary artery disease following lower extremity revascularisation (LER).
Following LER, patients with PAD are four times more likely to experience acute limb ischaemia, or a rapid decrease in lower limb blood flow, which is often associated with long hospitalisations and high incidences of amputation, disability, and death unless appropriate treatment is given.
Patients with PAD are also at a heightened risk of MACE, defined as MI, ischaemic stroke, or cardiovascular death. In this analysis, 14.1% of patients with PAD and coronary artery disease treated with rivaroxaban plus aspirin experienced a MACE versus 17.6% of patients treated with placebo (aspirin alone). In patients with PAD only, 11% of patients treated with rivaroxaban plus aspirin experienced a MACE versus 9.8% of patients treated with placebo. Overall, rivaroxaban plus aspirin showed a consistent benefit in reducing MACE in patients with and without coronary artery disease.
“These analyses reinforce the consistency of the favourable benefit-risk profile of Xarelto plus aspirin for patients with vascular disease, regardless of comorbidity. For example, patients categorised as ‘fragile’ are often undertreated due to concerns about benefit-risk, particularly with antithrombotic treatments,” said Marc Bonaca (University of Colorado Anschutz Medical Campus, Aurora, USA). “We hope the ongoing wealth of data coming from VOYAGER PAD presented at AHA offers clinicians the information they need to support shared decision-making in prescribing Xarelto plus aspirin as the standard of care for their PAD patients, including those who are high-risk or complex.”
In August 2021, the US Food and Drug Administration (FDA) approved an expanded PAD indication for Xarelto to include patients following a recent LER due to symptomatic PAD. Xarelto acts on a dual pathway inhibition (DPI) approach to target both clotting mechanisms, thrombin and platelet activation.