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)

On the rise but still underutilized – why statins are the Achilles’ heel of secondary prevention in peripheral arterial disease

“…Consequently, despite increasing prevalence efficient lipid management represents clearly the Achilles' heel of secondary prevention in symptomatic PAD. These findings for a German cohort are in line with striking results from an international meta-analysis on 19 studies and 26,985 patients, where only half of all patients with critical limb ischaemia received lipid-lowering drugs [2]. Interestingly, even among those treated with lipidlowering drugs the situation is far from satisfying.…”

Medical therapy for cardiovascular and limb-related risk reduction in critical limb ischemia

“…elderly), in an effort to optimize medical therapy for patients with CLI. 11 Contemporary studies investigating the outcomes of statin therapy in patients with CLI are presented in Table 1. 21–39…”

Nutrition, dietary habits, and weight management to prevent and treat patients with peripheral artery disease

“…Similarly, increased levels of vitamins K and E, with parallel administration of warfarin as anticoagulation therapy for PAD's comorbidities, have been associated with vascular calcification. Thus, patients on coumadin should be routinely monitored for these nutrient deficiencies and at the same time evaluated for candidacy for newer oral anticoagulants (Foley et al, 2017;Kokkinidis et al, 2020a;Siasos et al, 2020). Novel oral anticoagulants in combination with aspirin may provide an alternative treatment in PAD, however, it is deemed necessary to identify patient subgroups who will benefit the most (Koutsoumpelis et al, 2018).…”

“…The potential mechanism is explained by the fact that hyperparathyroidism increases the risk of osteomalacia and arterial calcification (Krishna, 2019). Folate and vitamin D deficiencies have been linked to an increased risk of PAD and worsening ambulatory sta-tus (Kokkinidis et al, 2020a). The Institute of Medicine's Food and Nutrition Board recommends consumption of 700 IU/day of vitamin D, 400 µg/day folate, 1.7 mg/day vitamin B6, 2.4 µg/day vitamin B12 and a daily maximum of 1250 mg sodium in patients with PAD (Nosova et al, 2015) (Table 1).…”