Clinical Edge

Summaries of Must-Read Clinical Literature, Guidelines, and FDA Actions

Rivaroxaban in Patients with Stable PAD

Lancet; 2018 Jan 20; Anand, Bosch, et al

In patients with stable peripheral or carotid artery disease, low-dose rivaboxaban taken twice a day plus aspirin once a day reduced major adverse cardiovascular (CV) and limb events when compared to aspirin alone, a recent study found. The double-blind, randomized, placebo-controlled international trial included patients from 602 hospitals. After a 30-day run-in period, patients were randomly assigned (1:1:1) to receive oral rivaroxaban twice daily plus aspirin once daily, rivaroxaban twice a day, or aspirin once a day. Among the details:

  • Between March 12, 2013, and May 10, 2016, 7,470 patients with PAD from 558 centers were enrolled.
  • The combination of rivaroxaban plus aspirin compared with aspirin alone reduced the composite endpoint of CV death, myocardial infarction (MI), or stroke (5% vs 7%, HR 0.72 (p=0.0047), and major adverse limb events including major amputation (1% vs 2%, HR 0.54, p=0.037).
  • Rivaroxaban 5 mg twice a day compared with aspirin alone did not significantly reduce the composite endpoint.
  • Rivaroxaban plus aspirin increased major bleeding vs aspirin alone group, primarily GI bleeding (3% vs 2%, HR 1.61, p=0.0089).


Anand SS, Bosch J, Eikelboom JW, et al. Rivaroxaban with or without aspirin in patients with stable peripheral or carotid artery disease: An international, randomized, double-blind, placebo-controlled trial. Lancet. doi:10.1016/S0140-6736(17)32409-1.


Patients with PAD and carotid disease usually have widespread atherosclerosis and are at high risk for developing additional vascular disease manifestations including MI and stroke. The current standard treatment for patients with stable non-surgical peripheral artery disease and carotid disease is antiplatelet therapy, smoking cessation, statins, lifestyle modification with exercise and diet, and control of hypertension and diabetes. The prespecified net clinical benefit—cardiovascular death, myocardial infarction, stroke, and fatal or critical organ bleeding—occurred in 6% of patients with low-dose rivaroxaban plus aspirin and in 7% of patients with aspirin alone (HR 0.75, p=0.011). The net clinical benefit outcome—major adverse cardiovascular events or major adverse limb events including major amputation, or fatal or critical organ bleeding—occurred in 7% of patients on rivaroxaban plus aspirin vs 9% in patients on aspirin alone (HR 0.72, p=0.0008). In a separate study, rivaroxaban (2.5 mg orally twice a day) plus aspirin (100 mg once a day) decreased recurrent MI and death, while increasing major bleeding, and reduced total mortality (HR 0.77, p=0.0012).1 This is an area to keep close watch of, and see how this data are integrated into major guidelines for the treatment of PAD and coronary disease. — Neil Skolnik, MD

  1. Connolly SJ, et al. Rivaroxaban with or without aspirin in patients with stable coronary artery disease: an international, randomised, double-blind, placebo-controlled trial. [Published online ahead of print November 10, 2017]. Lancet. doi:10.1016/ S0140-6736(17)32458-3.