MALE is associated with substantial increase in MACE and amputations in PAD patients

Introduction and methods

Peripheral artery disease (PAD) patients have a high risk of major adverse cardiovascular events (MACE) and major adverse limb events (MALE) due to widespread atherosclerosis. Results of the COMPASS trial showed that a combination of rivaroxaban 2.5 mg twice daily and aspirin lowered MACE and MALE in PAD patients compared to aspirin alone. MALE is not common and prognosis after MALE is not well documented and may be severe. Therefore, predictors of MALE, prognosis of PAD patients after a MALE event and impact of low dose rivaroxaban and aspirin compared to aspirin alone in the prevention of MALE, vascular interventions, and total peripheral vascular outcomes were analyzed.

COMPASS was a randomized double blind placebo controlled trial in which rivaroxaban 2.5 mg bid plus aspirin, rivaroxaban 5 mg bid, were each compared to aspirin alone in 27395 patients with coronary artery disease or PAD. In this sub-analysis of the COMPASS trial, 6391 patients with PAD of the lower extremity were included and followed for 23 months. MALE was defined as severe limb ischemia leading to an intervention or major amputation of a vascular cause. Outcomes evaluated after MALE included MACE, total amputation, and mortality.

Main results

• After a MALE event, MACE or total vascular amputations (HR 7.56, P<0.0001), all-cause mortality (HR 3.23, P<0.0001), hospitalization (HR 7.21, P<0.0001) and amputation (HR 197.5, P<0.0001) were increased compared to PAD patients who did not suffer a MALE event.
• The combination rivaroxaban plus aspirin reduced peripheral vascular outcomes compared to aspirin alone: MALE (HR 0.57; 95%CI:0.37-0.88, P=0.01), total vascular amputations (HR 0.42; 95%CI:0.21-0.85, P=0.01), major vascular amputations (HR 0.33; 95%CI:0.12-0.92, P=0.03), vascular interventions (HR 0.76; 95%CI:0.60-0.97, P=0.03) and total peripheral vascular outcomes (HR 0.76; 95%CI:0.61-0.96, P=0.02).
• Outcomes after MALE were worse in aspirin-treated patients compared to rivaroxaban plus aspirin-treated patients (for death: HR 5.97, P<0.0001 in aspirin only vs. HR 0.89, P=0.89 in rivaroxaban plus aspirin and for MACE and total amputations: HR 10.2, P<0.0001 in aspirin only vs. HR 2.05, P=0.32 in rivaroxaban plus aspirin).

Conclusion

Disclosures

Our coverage of ACC.18 is based on the information provided during the congress.