By Hannah Woolley
Findings from the Rivaroxaban for the Prevention of Major Cardiovascular Events in Coronary or Peripheral Artery Disease (COMPASS) trial suggest that the combination of low-dose rivaroxaban and aspirin significantly lowers the incidence of both major adverse cardiovascular events and major adverse limb events in patients with lower extremity peripheral artery disease. The results were published in the Journal of the American College of Cardiology. Rivaroxaban is currently used for stroke prevention in atrial fibrillation.
The study analysed outcomes in 6,391 patients with lower extremity peripheral artery disease who were randomised to receive either a low-dose rivaroxaban (2.5 mg/twice daily) and aspirin combination, rivaroxaban alone, or aspirin alone. Researchers looked to see if hospitalisations, major adverse cardiovascular events, amputations and deaths were higher after the first episode of major adverse limb events compared with peripheral artery disease patients who did not experience major adverse limb events. They also studied the impact of treatment with low-dose rivaroxaban and aspirin compared with aspirin alone on the incidence of major adverse limb events, peripheral vascular interventions, and all peripheral vascular outcomes over a median follow-up of 21 months.
Researchers found the independent predictors of major adverse limb events included “severe ischaemia symptoms at baseline, prior limb or foot amputation at baseline, prior history of peripheral revascularisation surgery or angioplasty, and randomisation to the aspirin arm of trial.” They noted that diabetes, smoking, female sex and history of peripheral artery disease were not independently predictive of major adverse limb events. Overall, the incidence of major adverse limb events was highest (3.8%) in peripheral artery disease patients with a prior history of intervention (i.e., peripheral revascularisation or amputation) and lowest (0.5%) in patients with asymptomatic peripheral artery disease (Ankle-brachial index<0.90).
According to researchers, 128 patients experienced major adverse limb events, putting them at significantly increased one-year cumulative risk of subsequent hospitalisations (95.4%), amputations (22.9%) and death (8.7%). However, compared with aspirin alone, the combination of rivaroxaban and aspirin lowered the incidence of major adverse limb events by 43% (p=0.01), total vascular amputations by 58 % (p=0.01), peripheral vascular interventions by 24% (p=0.03) and all peripheral vascular outcomes by 24% (p=0.02).
Of note, researchers said that “While the risk of death did not change after a major adverse limb event in participants randomised to receive rivaroxaban and aspirin combination, there was a sixfold risk of death after a major adverse limb event for participants randomised to receive aspirin alone.” Similarly, the risk of composite major adverse cardiovascular events or total vascular amputation in participants randomised to receive aspirin alone was 10-fold following a major adverse limb event.
“Among individuals with stable lower extremity peripheral artery disease, the development of major adverse limb events is associated with a dire prognosis, making its prevention of utmost importance,” researchers say. As such, they urge consideration of low-dose rivaroxaban and aspirin “As an important therapy for patients with peripheral artery disease.”
The dosage of 2.5 mg twice-daily rivaroxaban used together with aspirin, lower than the one currently approved for stroke prevention in atrial fibrillation, may have hit the sweet spot. It balances efficacy and safety by favourably affecting the residual risk in patients with established stable cardiovascular disease on an appropriate background medical regimen.