Major Adverse Limb Events in Lower Extremity Peripheral Artery Disease: COMPASS Trial

Abstract Background Patients with lower extremity peripheral artery disease (PAD) are at increased risk of major adverse cardiovascular events (MACE) and major adverse limb events (MALE). There is limited information on the prognosis of patients who suffer MALE. Objectives Among participants with lower extremity PAD, we investigated: 1) if hospitalizations, MACE, amputations, and deaths are higher after first episode of MALE compared with PAD patients who do not experience MALE and 2) the impact of treatment with low dose rivaroxaban and aspirin compared to aspirin alone on the incidence of MALE, peripheral vascular interventions, and all peripheral vascular outcomes over a median follow-up of 21 months. Methods We analyzed outcomes in 6,391 patients with lower extremity PAD who were enrolled in the COMPASS trial - a randomized double blind placebo controlled trial of low dose rivaroxaban and aspirin combination, rivaroxaban alone, as compared to aspirin alone. MALE was defined as severe limb ischemia leading to an intervention or major vascular amputation. Results A total of 128 patients suffered an incident MALE. After MALE, the one year cumulative risk of a subsequent hospitalization was 95.4%, for vascular amputations it was 22.9%, for death it was 8.7%, and for MACE it was 3.8%. The MALE index event significantly increased the risk to experience subsequent hospitalizations (HR 7.21; P Summary Among individuals with lower extremity PAD, the development of MALE is associated with a poor prognosis, making its prevention of utmost importance. The combination of rivaroxaban 2.5 mg bid and aspirin significantly lowers the incidence of MALE and its related complications and should be considered as an important therapy for patients with PAD. Clinical trial This is a subgroup analysis of a clinical trial called COMPASS registered on clinical trials.gov.