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 experience MALE.
OBJECTIVES Among participants with lower extremity PAD, this study investigated: 1) if hospitalizations, MACE,
amputations, and deaths are higher after the first episode of MALE compared with patients with PAD who do not
experience MALE; and 2) the impact of treatment with low-dose rivaroxaban and aspirin compared with 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
(Cardiovascular Outcomes for People Using Anticoagulation Strategies) trial. COMPASS was a randomized, double-blind
placebo-controlled study of low-dose rivaroxaban and aspirin combination or rivaroxaban alone compared with aspirin
alone. MALE was defined as severe limb ischemia leading to an intervention or major vascular amputation.
RESULTS A total of 128 patients experienced an incident of MALE. After MALE, the 1-year cumulative risk of a subsequent
hospitalization was 61.5%; for vascular amputations, it was 20.5%; for death, it was 8.3%; and for MACE, it was
3.7%. The MALE index event significantly increased the risk of experiencing subsequent hospitalizations (hazard ratio
[HR]: 7.21; p < 0.0001), subsequent amputations (HR: 197.5; p < 0.0001), and death (HR: 3.23; p < 0.001). Compared
with aspirin alone, the combination of rivaroxaban 2.5 mg twice daily and aspirin lowered the incidence of MALE by 43%
(p ¼ 0.01), total vascular amputations by 58% (p ¼ 0.01), peripheral vascular interventions by 24% (p ¼ 0.03), and all
peripheral vascular outcomes by 24% (p ¼ 0.02).
CONCLUSIONS Among individuals with lower extremity PAD, the development of MALE is associated with a poor
prognosis, making prevention of this condition of utmost importance. The combination of rivaroxaban 2.5 mg twice daily
and aspirin significantly lowered the incidence of MALE and the related complications, and this combination should be
considered as an important therapy for patients with PAD. (Cardiovascular Outcomes for People Using Anticoagulation
Strategies [COMPASS]; NCT01776424) (J Am Coll Cardiol 2018;71:2306–15) © 2018 by the American College of