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Decreasing Risk of Lower Extremity Amputation

What should you add to prevent a loss of limb?

Amputations can be a major potential complication of diabetes. Only a small percentage of people diagnosed with diabetes require amputations, diabetic patients still account for approximately 60% of non-traumatic lower-limb amputations performed in people over the age of 20. Since diabetes is a major risk factor for peripheral arterial disease (PAD), it is important to properly manage PAD in order to reduce complications down the rode in diabetes patients. Although statins are recommended for PAD patients, there is little research as to whether statins are an effective option to aid the prevention of amputations in type 2 diabetes patients.

Researchers used data from Taiwan’s National Health Insurance Research Database (NHIRD) to “investigate whether the use of statins is associated with a lower extremity amputation rate in a high risk population with known PAD as compared to two propensity score-matched cohorts without statin use while taking into consideration the competing risk of death.” The study population included patients who were age 20 or older with a diagnosis of both diabetes mellitus and peripheral arterial disease during the search period and had 5 years of data before inclusion in the study.  Patients were then divided into three groups based on current PAD treatment: statin-user, non-statin lipid-lowering agent, or non-user. Patients who were excluded from the study were those who were on a combination of statins and other lipid-lowering agents. A propensity score was calculated for patients to determine the probability of a patient receiving a lipid-lowering agent and control patients were matched to both statin and non-statin users with a similar propensity. The primary outcome of the study was new lower extremity amputation and secondary outcomes were in-hospital cardiovascular death and all-cause mortality.

The study included a total of 69,332 diabetes patients with a mean age of 62.6 years who were diagnosed with PAD during the study period.  The majority of the patients, approximately 77%, were non-users of lipid-lowering agents, 17% of the patients were statin users, and 6% used non-statin lipid-lowering agents. Over approximately 5.7 years of follow up, patients in the statin user group had less incidence of any lower extremity amputation, less total lower extremity amputation, and less in-hospital cardiovascular death and all-cause mortality compared to non-users. After adjusting for relevant factors, statin users had significantly lower risk of lower extremity amputation events (adjusted HR [aHR] 0.75, 95% CI 0.62-0.90) and significantly lower risk of total lower extremity amputations (aHR 0.58, 95% CU 0.36-0.93) when compared to non-users. In comparison, non-statin lipid-lowering agents were not associated with any significant decrease in lower extremity amputation events (aHR 0.95, 95% CI 0.73-1.23) and both the statin user group and non-statin lipid-lowering agent group. For the propensity score-matched analysis, 11,373 patients from both the statin user group and non-user group were matched and 4,428 patients from both the non-statin lipid-lowering agent group and the non-user group were matched. In the propensity score-match analysis, the statin user group had a 25% lower risk of any lower extremity amputation (HR 0.75, 95% CI 0.60-0.94), 52% lower total extremity amputation (HR 0.48, 95% CI 0.28-0.83), lower in-hospital cardiovascular death (HR 0.75, 95% CI 0.66-0.87), and lower all-cause mortality (HR 0.72, 95% CI 0.67-0.77) when compared to matched non-users, while non-statin lipid-lowering agents had a neutral effect on all outcomes compared to matched non-users. Other factors, such as gender, age> 65, hypertension, heart failure, CAD, use of antiplatelet drugs, and use of a high potency statin showed no significant effects on the outcome of the study.

Statins have known pleiotropic effects that aid in its protective effects for lowering risk of amputations in diabetes mellitus patients. While this study had a very large sample size, further studies may be needed in varying populations to determine relative effect and real world practice application.

Practice Pearls:

  • Statins can decrease the risk of lower limb amputation in diabetes mellitus patients with peripheral arterial disease.
  • Non-statin lipid lowering agents are not as beneficial as statins in decreasing the risk for lower limb amputations.
  • Statins should be combined with diet, exercise, and regular foot checks for the best outcome.



“Statistics About Diabetes.” American Diabetes Association. Web.

Hsu, Chien-Yi, Yung-Tai Chen, Yu-Wen Su, Chun-Chin Chang, Po-Hsun Huang, and Shing-Jong Lin. “Statin therapy reduces future risk of lower limb amputation in patient with diabetes and peripheral artery disease.” The Journal of Clinical Endocrinology & Metabolism (2017). Web.

Priscilla Rettman, BS, PharmD Candidate 2017, Philadelphia College of Osteopathic Medicine – GA Campus