Association of Statin Dose With Amputation and Survival in Patients With Peripheral Artery Disease
Open accessAbstract
Background: Statin dose guidelines for patients with peripheral artery disease (PAD) are largely based on coronary artery disease and stroke data. The aim of this study is to determine the effect of statin intensity on PAD outcomes of amputation and mortality. Methods: Using an observational cohort study design and a validated algorithm, we identified patients with incident PAD (2003–2014) in the national Veterans Affairs data. Highest statin intensity exposure (high-intensity versus low-to-moderate–intensity versus antiplatelet therapy but no statin use) was determined within 1 year of diagnosis of PAD. Outcomes of interest were lower extremity amputations and death. The association of statin intensity with incident amputation and mortality was assessed with Kaplan-Meier plots, Cox proportional hazards modeling, propensity score–matched analysis, and sensitivity and subgroup analyses, as well, to reduce confounding. Results: In 155 647 patients with incident PAD, more than a quarter (28%) were not on statins. Use of high-intensity statins was lowest in patients with PAD only (6.4%) in comparison with comorbid coronary/carotid disease (18.4%). Incident amputation and mortality risk declined significantly with any statin use in comparison with the antiplatelet therapy–only group. In adjusted Cox models, the high-intensity statin users were associated with lower amputation risk and mortality in comparison with antiplatelet therapy–only users (hazard ratio, 0.67; 95% confidence interval, 0.61–0.74 and hazard ratio, 0.74; 95% confidence interval, 0.70–0.77, respectively). Low-to-moderate–intensity statins also had significant reductions in the risk of amputation and mortality (hazard ratio amputation, 0.81; 95% confidence interval, 0.75– 0.86; hazard ratio death, 0.83; 95% confidence interval, 0.81–0.86) in comparison with no statins (antiplatelet therapy only), but effect size was significantly weaker than the high-intensity statins ( P <0.001). The association of high-intensity statins with lower amputation and death risk remained significant and robust in propensity score–matched, sensitivity, and subgroup analyses. Conclusions: Statins, especially high-intensity formulations, are underused in patients with PAD. This is the first population-based study to show that high-intensity statin use at the time of PAD diagnosis is associated with a significant reduction in limb loss and mortality in comparison with low-to-moderate–intensity statin users, and patients treated only with antiplatelet medications but not with statins, as well.
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In a study using a large administrative dataset from the VA, including >24,000 Black Americans, there was a similar 33% reduction in amputation with high-intensity statin in Black compared with NHW patients.
“In a study using a large administrative dataset from the VA, which included >24 000 Black Americans, there was a similar 33% reduction in amputation with high-intensity statin in Black compared with NHW patients.69”
From Racial and Ethnic Disparities in Peripheral Artery Disease (2021) · cites this paper as [69]
Methods (Sample and Database) identifies a national VA cohort of 155,647 patients. Results (Adjusted associations) reports a 33% lower amputation risk with high-intensity statins for the overall cohort, and Results (Subgroup Analysis) says Black and white patients had similar reductions. Our copy does not establish that the cohort included more than 24,000 Black patients or report an exact 33% reduction specifically for Black patients. (LLM, conf=0.86)
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- [22]Arya S Binney Z Khakharia A Brewster LP Wilson PWF Goodney PP Peripheral arterial disease (PAD) variability in diagnosis: The Veterans Affairs (VA) population experience (abstract) Association of VA Surgeons 40th Annual Surgical Symposium 2016
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- Authors
- Arya, S., Khakharia, A., Binney, Z. O., DeMartino, R. R., Brewster, L. P., Goodney, P. P., & Wilson, P. W. F.
- Affiliations
- Emory University (US)
- Division of Vascular Surgery and Endovascular Therapy, Department of Surgery (S.A., A.K., L.P.B.)
- Mayo Clinic (US)
- Dartmouth–Hitchcock Medical Center (US)
- Atlanta VA Medical Center (US)
- ORCID
- Venue
- Circulation
- Published
- 2018-04-03
- Volume
- 137
- Issue
- 14
- Pages
- 1435-1446
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- PMC
- PMC5882502
- OpenAlex
- W2783484560
- Semantic Scholar
- ec30992a826a86e73e1e2cb01f9dc93ab9faea2d
- Cited by
- 257
- References
- 44
- Citations by year
- 2026: 20 · 2025: 25 · 2024: 32 · 2023: 24 · 2022: 43 · 2021: 38 · 2020: 32 · 2019: 32 · 2018: 11
- FWCI
- 29.37
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Department of Veterans Affairs (I01 CX001025)
- National Institute on Aging (R03AG050930)
- National Heart, Lung, and Blood Institute (K08HL119592)
- Topics
- Health Sciences › Medicine › Surgery › Peripheral Artery Disease Management
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Antiplatelet Therapy and Cardiovascular Diseases
- Keywords
- statin dose, statin intensity, peripheral arterial disease, lower limb amputation, mortality, antiplatelet therapy, veterans, cardiovascular risk reduction
- MeSH terms
- Aged, Amputation, Surgical, Dose-Response Relationship, Drug, Female, Humans, Male, Middle Aged, Platelet Aggregation Inhibitors, Risk Factors, Comorbidity, Proportional Hazards Models, Treatment Outcome, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Kaplan-Meier Estimate, Propensity Score, Peripheral Arterial Disease
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