Recently, increased risk of amputation has been debated under SGLT2 inhibitors. These drugs have diuretic properties and one can suggest whether other “traditional” diuretics could have similar concerns. The goal of this review was to collect all available data on any potential risk of amputation associated to diuretics in patients with lower-extremity artery disease (LEAD). Additionally, we looked for other limb or cardiovascular events.

We searched in PubMed, Embase and Scopus databases up to February 2021 for references using peripheral or lower-extremity artery disease, diuretics, and amputation keywords, excluding case reports as well as experimental animal studies and non-English reports.

Among the 1376 hits found in the databases, six publications were finally included in this review, including one cross-sectional and five longitudinal studies (total of 47,612 participants). In the univariate analysis of 3 studies, diuretic use was associated with amputations. In multivariate analysis, 5 studies reported a higher rate of amputation in diuretic users than in non-users. Some have shown an increased amputation risk according to thiazide diuretics and loop diuretics, while the remaining ones mixed all diuretics. All reported a significant association between diuretic use and amputation risk; the most recent shows a HR=1.89 (95% CI: 1.34–2.68). Beyond amputation, patients with LEAD under diuretics appeared as being at increased risk of other lower limb events or cardiovascular events, mostly with comorbidities including diabetes mellitus.

All studies identified in this first systematic review are consistent in favor of an increased risk of amputation in patients with (or at risk of) LEAD under diuretics. Further studies must be conducted to provide a better understanding of the mechanisms.