Statin therapy for reduction of cardiovascular and limb-related events in critical limb ischemia: A systematic review and meta-analysis

Abstract

High-intensity statins are recommended for patients with peripheral artery disease (PAD). Critical limb ischemia (CLI) is the most advanced presentation of PAD. The benefit of statins in the CLI population is unclear based on the existent studies. Our objective was to perform a systematic review and meta-analysis regarding the efficacy of statin therapy in patients with CLI. PRISMA guidelines were followed. PubMed, EMBASE, and Cochrane CENTRAL databases were reviewed up to April 30, 2019. The primary outcomes included amputation rates and all-cause mortality. Secondary outcomes included primary patency rates, amputation-free survival and major adverse cardiac or cerebrovascular events (MACCE). Risk of bias was assessed with the Robins-I tool for observational studies. A random-effects model meta-analysis was performed. Heterogeneity was assessed with I2. Funnel plots and Egger’s test were used to assess publication bias. Nineteen studies including 26,985 patients with CLI were included in this systematic review. Among patients with known data on statin status, 12,292 (49.6%) were on statins versus 12,513 (50.4%) not on statins. Patients treated with statins were 25% less likely to undergo amputation (HR 0.75; 95% CI: 0.59–0.95; I2 = 79%) and 38% less likely to have a fatal event (HR 0.62; 95% CI: 0.52–0.75; I2 = 41.2%). Statin therapy was also associated with increased overall patency rates and lower incidence of MACCE. There was substantial heterogeneity in the analysis for amputation and amputation-free survival (I2 > 70%). In conclusion, statins are associated with decreased risk for amputation, mortality, and MACCE, as well as increased overall patency rates among patients with CLI. Future studies should assess whether other lipid-lowering medications in addition to high-intensity statins can further improve outcomes among patients with CLI. (PROSPERO registration number: CRD42019134160)