Etiology and Outcomes of Amputation in Patients with Peripheral Artery Disease: Insights from the EUCLID Trial.

Abstract Objective Amputation remains a frequent and feared outcome in patients with peripheral artery disease (PAD). While typically characterized as major or minor on the extent of tissue loss, the etiologies and outcomes after amputation by extent are not well understood. In addition, emerging data suggest that the drivers and outcomes of amputation in PAD may differ in those with and without diabetes mellitus (DM). Methods The EUCLID trial randomized 13,885 patients with symptomatic PAD, including 5,345 with concomitant diabetes, to ticagrelor or clopidogrel and followed for long-term outcomes. Amputations were prospectively reported by trial investigators. Their primary and contributing drivers were adjudicated using safety data including infection, ischemia, or multifactorial etiologies. Outcomes following major and minor amputations were analyzed including recurrent amputation, major adverse limb events (MALE), adverse cardiovascular events and mortality. Multivariable logistic regression models were used to identify independent predictors of minor amputations. Analyses were performed overall and stratified by the presence or absence of diabetes mellitus (DM) at baseline. Results Of the patients randomized, 398 (2.9%) underwent at least one lower extremity non-traumatic amputation for a total of 511 amputations (255 major and 256 minor) over a median of 30 months. A history of minor amputation was the strongest independent predictor for a subsequent minor amputation (OR 7.29, 95% CI 5.17-10.30; p Conclusions Outcomes after amputation remain poor regardless of whether categorized as major or minor. The pattern of amputation drivers in PAD differs by history of DM with infection being the dominant etiology in those with DM and ischemia in those without DM. Greater focus is needed on the prognostic importance of minor amputation and of the multifactorial etiologies of amputation in PAD. Nomenclature with anatomical description of amputations and eliminating terms “major” or “minor” would seem appropriate.