Protective Effects of Statins on Limb and Cardiovascular Outcomes in Patients with Peripheral Artery Disease and End-Stage Renal Disease

Abstract

Background: Previous studies have reported that statins have inconsistent and marginal cardiovascular (CV) benefits in patients with end-stage renal disease (ESRD). However, whether statins play a secondary preventive role in patients with peripheral artery disease (PAD) and ESRD remains unclear.

Objectives: This study aimed to compare the long-term clinical outcomes between statin users and nonusers with PAD and ESRD.

Methods: This retrospective cohort study assessed the long-term protective effects of statins using data from the National Health Insurance Research Database in Taiwan. Propensity score matching was performed according to sex, age, index year, related comorbidities, and medications. The main outcomes were limb events and major adverse CV events (MACEs).

Results: The statin user group (n = 4,460) was compared with the propensity score-matched statin nonuser group (n = 4,460). The mean age of the matched patients was 64 years, and 40% of the patients were men. The baseline characteristics of the groups were well-balanced. The overall limb event and MACE rates were not different between the two groups. However, the statin user group had lower rates of limb amputation [adjusted hazard ratio (aHR): 0.85, 95% confidence interval (CI): 0.73-0.99], stroke (aHR: 0.71, 95% CI: 0.62-0.83), CV death (aHR: 0.46, 95% CI: 0.32-0.66), and all-cause death (aHR: 0.45, 95% CI: 0.42-0.48) despite having a higher rate of percutaneous transluminal angioplasty for PAD.

Conclusions: This population-based retrospective cohort study demonstrated that statin therapy was associated with a lower risk of limb amputation, nonfatal stroke, CV death, and all-cause death in patients with PAD and ESRD.

Keywords: Amputation; Cardiovascular event; ESRD; Limb event; PAD; Statin.

Figure 1

Flowchart of patient flow using propensity score matching by gender, age, related comorbidities, and related medications after applying exclusion criteria. ESRD, end-stage renal disease; NHIRD, National Health Insurance Research Database; PAD, peripheral artery disease.

Figure 2

Forest plot of the adjusted hazard ratio for limb events between statin users and nonusers in different subgroups. aHR, adjusted hazard ratio; CI, confidence interval; DM, diabetes mellitus; PTA, percutaneous transluminal angioplasty.

Figure 3

Forest plot of the adjusted hazard ratio for MACE between statin users and nonusers in different subgroups. aHR, adjusted hazard ratio; AMI, acute myocardial infarction; CI, confidence interval; CV, cardiovascular; DM, diabetes mellitus; MACE, major adverse cardiovascular events.

Figure 4

Forest plot of the adjusted hazard ratio for all-cause death between statin users and nonusers in different subgroups. aHR, adjusted hazard ratio; CI, confidence interval; DM, diabetes mellitus.

Central illustration

Schematic representation of the research design and findings exploring the influence of statins on limb events, MACE, and overall mortality among patients with ESRD and PAD. aHR, adjusted hazard ratio; AMI, acute myocardial infarction; CI, confidence interval; CV, cardiovascular; ESRD, end-stage renal disease; HF, heart failure; IHD, ischemic heart disease; MACE, three-points major adverse cardiovascular events; PAD, peripheral artery disease; PTA, percutaneous transluminal angioplasty.