Higher-Dose Statins Reduced All-Cause Mortality, Amputation Risk in PAD

Higher doses of statins may more effectively prevent adverse clinical outcomes in PAD.

According to results of a systematic review and meta-analysis, published in the European Journal of Vascular and Endovascular Surgery, higher-dose statin therapy for patients with peripheral arterial disease (PAD) greatly reduced all-cause mortality and amputation risk.

Researchers from Colchester General Hospital and Addenbrooke’s Hospital in the United Kingdom searched publication databases through February 2020 for studies examining statin use in patients with PAD. Clinical outcomes based on the American College of Cardiology and American Heart Association classification scheme for low, moderate, and high intensity statin therapies were assessed.

A total of 24 studies of cohort (n=22), retrospective (n=13), and prospective (n=9) designs were included in this analysis.

Among all statin users, risk for all-cause mortality (n=87,917; odds ratio [OR], 0.68; 95% CI, 0.60-0.76; I2, 56%), major adverse cardiac events (n=20,748; OR, 0.84; 95% CI, 0.78-0.92; I2, 45%), amputation (n=72,325; OR, 0.59; 95% CI, 0.33-1.07; I2, 86%), and cardiovascular mortality (n=78,273; OR, 0.55; 95% CI, 0.38-0.78; I2, 90%) were reduced among the statin recipients compared with individuals who did not receive statins.

The studies reporting hazard ratios (HRs) showed similar reductions in mortality (n=10; HR, 0.74; 95% CI, 0.70-0.78; I2, 19%), major adverse cardiac events (n=2; HR, 0.78; 95% CI, 0.65-0.93), amputation (n=4; HR, 0.64; 95% CI, 0.53-0.78; I2, 81%), and cardiovascular mortality (n=5; HR, 0.70; 95% CI, 0.48-1.04; I2, 86%).

Stratified by statin dosage, higher doses were associated with further decreases in mortality (HR, 0.74; 95% CI, 0.62-0.89), amputation (HR, 0.78; 95% CI, 0.69-0.90), and cardiovascular mortality (HR, 0.71; 95% CI, 0.63-0.80),

This study was limited by the moderate homogeneity observed among the underlying studies. Additional large, registry-based studies are needed to confirm these findings.

These data indicated that higher-dose statin therapies for patients with PAD likely result in a greater reduction in risk for poor clinical outcomes compared with low-dose or non-statin therapies.


Sofat S, Chen X, Chowdhury MM, Coughlin PA. Effects of Statin Therapy and Dose on Cardiovascular and Limb Outcomes in Peripheral Arterial Disease: A Systematic Review and Meta-analysis. Eur J Vasc Endovasc Surg. 2021;62(3):450-461.