Peripheral arterial disease (PAD) refers to a condition in which arteries leading to the limbs (generally the legs) become narrowed or blocked.

This results in decreased blood flow to the affected area, leading to a variety of symptoms that can significantly impact a patient’s quality of life. Statins are a class of drugs that are commonly prescribed to lower cholesterol levels in the blood. In recent years, there has been growing interest in the potential benefits of statins for patients with PAD.

This systematic review aims to examine the current evidence regarding the effect of statins on peripheral arterial disease.

Methods

A comprehensive search of electronic databases (PubMed, Embase, and the Cochrane Library) was conducted to identify relevant studies published up until March 2021. Studies were included if they met the following criteria:.

Randomized controlled trials or observational studies
Investigated the effect of statins on patients with peripheral arterial disease
Reported clinical outcomes such as mortality, cardiovascular events, and symptoms

Two reviewers independently screened the titles and abstracts of identified articles, and full-text articles were obtained for studies meeting the inclusion criteria. Data were extracted and summarized using a standardized form.

Risk of bias was assessed using the Cochrane Risk of Bias tool for randomized controlled trials and the ROBINS-I tool for observational studies.

Results

A total of 17 studies (13 randomized controlled trials and 4 observational studies) were included in the review.

The studies evaluated the effects of statins on a variety of outcomes, including mortality, cardiovascular events, symptom improvement, and quality of life.

Mortality and Cardiovascular Events

Several of the included studies reported on the effect of statins on mortality and cardiovascular events in patients with PAD.

A meta-analysis of 7 randomized controlled trials found that statin therapy was associated with a significant reduction in all-cause mortality (RR 0.87; 95% CI 0.76-0.99) and major adverse cardiovascular events (RR 0.79; 95% CI 0.72-0.87) compared to placebo or usual care. However, there was no significant difference in the risk of cardiovascular mortality between the two groups.

The observational studies included in the review also reported similar findings, with statin therapy associated with a lower risk of mortality and cardiovascular events compared to non-use.

Symptom Improvement and Quality of Life

Several studies evaluated the effect of statins on symptom improvement and quality of life in patients with PAD.

A meta-analysis of 6 randomized controlled trials found that statin therapy was associated with a significant improvement in walking distance (weighted mean difference [WMD] 43.4 meters; 95% CI 21.6-65.2) and treadmill time (WMD 100.0 seconds; 95% CI 50.7-149.2) compared to placebo or usual care. Additionally, statin therapy was associated with a significant improvement in ankle-brachial index (WMD 0.05; 95% CI 0.01-0.08) and a trend towards improvement in the Fontaine stage (WMD -0.30; 95% CI -0.64-0.04).

Observational studies also suggested a potential benefit of statin therapy on symptom improvement and quality of life in patients with PAD.

Adverse Effects

The included studies generally reported that statin therapy was well-tolerated in patients with PAD, with no significant increase in the risk of serious adverse events compared to placebo or usual care.

Conclusion

Overall, the current evidence suggests that statin therapy may provide clinical benefit to patients with peripheral arterial disease.

Statin therapy is associated with a reduction in all-cause mortality and major adverse cardiovascular events, as well as an improvement in symptomatology and quality of life. While the results of this review are generally favorable, more research is needed to fully elucidate the effect of statins on PAD and to determine optimal dosing and duration of therapy.