Statin Therapy Reduces Future Risk of Lower-Limb Amputation in Patients With Diabetes and Peripheral Artery Disease
Open accessAbstract
Context: Although there is evidence to support the beneficial effects of statins on major cardiovascular events, few studies address the protective effect of statins on limb outcome. Objective: To investigate whether the use of statin is associated with a risk reduction in lower-extremity amputation in type 2 diabetes mellitus (DM) patients with peripheral arterial disease (PAD). Design: Observational cohort study. Setting: A nationwide DM database in Taiwan from 2000 to 2011. Patients: A total of 69,332 patients aged ≥20 years with DM and PAD were identified. Intervention: Patients were divided into three groups: 11,409 patients were statin users, 4430 patients used nonstatin lipid-lowering agents, and 53,493 patients were nonusers. Main Outcome Measures: The primary outcome was lower-extremity amputation. Secondary outcomes were in-hospital cardiovascular death and all-cause mortality. Results: Compared with nonusers, statin users were associated with lower risks of lower-extremity amputation [adjusted hazard ration (aHR), 0.75; 95% confidence interval (CI), 0.62 to 0.90], in-hospital cardiovascular death (aHR, 0.78; 95% CI, 0.69 to 0.87), and all-cause mortality (aHR, 0.73; 95% CI, 0.69 to 0.77). In the propensity score matching analysis, the effect of statin on the risk of lower-extremity amputation was consistent. Only statin users were associated with the risk reduction of lower-extremities amputation (HR, 0.77; 95% CI, 0.61 to 0.97) and cardiovascular death (HR, 0.78; 95% CI, 0.68 to 0.89) when taking competing risk of death into consideration. Conclusions: Compared with statin nonusers who were never treated with lipid-lowering drugs, this study found that statin users had a lower risk of lower-extremity amputation and cardiovascular death in patients with DM and PAD.
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Several observational studies have shown that statins reduce the rate of amputation with relative risk reductions between 18% and 35% that are not seen with the use of nonstatin lipid-lowering therapies.
“Several observational studies have shown that statins reduce the rate of amputation with relative risk reductions between 18% and 35% that are not seen with the use of nonstatin lipid-lowering therapies such as fibrates, bile acid sequestrants, nicotinic acid, and cholesterol absorption inhibitors.67,68”
From Racial and Ethnic Disparities in Peripheral Artery Disease (2021) · cites this paper as [67]
The Results report a 25% lower risk of any lower-extremity amputation among statin users, without a significant reduction among nonstatin users. The Discussion reports a 35% reduction in another observational study, but its 18% figure is for a composite of limb outcomes, including revascularization and ischemic amputation—not amputation alone. The cited paper therefore does not establish the full 18%–35% range specifically for amputation. (LLM, conf=0.86)
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- Authors
- Hsu, C.-Y., Chen, Y.-T., Su, Y.-W., Chang, C.-C., Huang, P.-H., & Lin, S.-J.
- Affiliations
- Taipei Medical University Hospital (TW)
- Taipei Municipal YangMing Hospital (TW)
- Taipei Veterans General Hospital (TW)
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2017-04-07
- Volume
- 102
- Issue
- 7
- Pages
- 2373-2381
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2604850438
- Semantic Scholar
- 895592ff45da45ad117b8ffb0966e234a59e23f2
- Cited by
- 89
- References
- 32
- Citations by year
- 2026: 4 · 2025: 11 · 2024: 8 · 2023: 8 · 2022: 15 · 2021: 8 · 2020: 16 · 2019: 12 · 2018: 6 · 2017: 1
- FWCI
- 9.80
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Health and Welfare (MOHW104‐TDU‐B‐211‐113‐003)
- Taipei Veterans General Hospital
- Topics
- Health Sciences › Medicine › Surgery › Peripheral Artery Disease Management
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetic Foot Ulcer Assessment and Management
- Keywords
- statins, lower limb amputation, type 2 diabetes, peripheral arterial disease, cardiovascular mortality, all-cause mortality, lipid-lowering drugs, limb salvage, competing risk of death
- MeSH terms
- Aged, Amputation, Surgical, Diabetes Mellitus, Type 2, Diabetic Angiopathies, Female, Follow-Up Studies, Humans, Male, Middle Aged, Retrospective Studies, Taiwan, Cohort Studies, Comorbidity, Incidence, Confidence Intervals, Survival Analysis, Databases, Factual, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Lower Extremity, Risk Reduction Behavior, Propensity Score, Peripheral Arterial Disease
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