Statin use and lower extremity amputation risk in nonelderly diabetic patients

Abstract

Objective To examine the association between use of statin and non-statin cholesterol-lowering medications and risk of nontraumatic major lower-extremity amputations (LEA) and treatment failure (LEA or death). Design of Study A retrospective cohort of patients with Type I and Type 2 diabetes mellitus (diabetes) was followed for five years between 2004 and 2008. The follow-up exposure duration was divided into 90-day periods. Use of cholesterol-lowering agents, diabetic medications, hemoglobin A1c, body mass index, and systolic and diastolic blood pressures were observed in each period. Demographic factors were observed at baseline. Major risk factors of LEA including peripheral neuropathy, PAD, and foot ulcers were observed at baseline and were updated for each period. LEA and deaths were assessed in each period and their hazard ratios were estimated. Setting US Department of Veterans Affairs Healthcare system (VA) Subjects Cholesterol drug-naïve patients with Type I or II diabetes who were treated in the VA in 2003 and were <65 years old at the end of follow-up. Results Of 83,593 patients in the study cohort, 217 (0.3%) patients experienced a major LEA and 11,716 (14.0%) patients experienced an LEA or death (treatment failure) after a mean follow-up of 4.6 years. Compared to patients who did not use cholesterol-lowering agents, statin users were 35% - 43% less likely to experience an LEA (HR = 0.65; 95% CI, 0.42–0.99) and a treatment failure (HR = 0.57; 95% CI, 0.54–0.60). Users of other cholesterol-lowering medications were not significantly different in LEA risk (HR = 0.95; 95% CI, 0.35–2.60) but had a 41% lower risk of treatment failure (HR = 0.59; 95% CI, 0.51–0.68). Conclusions This is the first study to report a significant association between statin use and diminished amputation risk among patients with diabetes. In this non-randomized cohort, beneficial effects of statin therapy were similar to that seen in large-scale clinical trial experience. For LEA risk, those given non-statins did not have a statistically significant benefit and its effect on LEA risk was much smaller compared to statins.. Unanswered questions to be explored in future studies include a comparison of statins of moderate versus high potency in those with high risk of coronary heart disease and an exploration of whether the effects seen in this study are simply effects of cholesterol-lowering or possibly pleiotropic effects.

Statin use and other factors associated with mortality after major lower extremity amputation

“…[8][9][10] Multiple studies have shown that statin use is associated with lower rates of LEA. 11,12 No association between statin therapy and mortality has been shown in LEA patients. In 2013 the American College of Cardiology (ACC) and the American Heart Association (AHA) released guidelines on the "Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults."…”

Atherosclerosis risk factors in male patients qualified for percutaneous stenting of lower extremity arteries. A retrospective cohort study

“…In addition, several studies in recent years have shown that statins improved pain-free walking distance, anklebrachial index values and treadmill exercise time [8,36]. Although Dosluoglu et al [37] did not find a favorable statins effect on long-term stent or bypass patency and limb salvage, Sohn et al [38] reported that compared with patients who did not use cholesterollowering agents statin users were 35-43% less likely to experience lower extremity amputation. In this study, users of other cholesterol-lowering medications were not significantly different in terms of leg amputation risk [38].…”

“…Although Dosluoglu et al [37] did not find a favorable statins effect on long-term stent or bypass patency and limb salvage, Sohn et al [38] reported that compared with patients who did not use cholesterollowering agents statin users were 35-43% less likely to experience lower extremity amputation. In this study, users of other cholesterol-lowering medications were not significantly different in terms of leg amputation risk [38]. Moreover, in another study, statin-treated patients with PAD after endovascular intervention had significantly higher rates of primary patency at 24 months (43% vs 33%), secondary patency (66% vs 51%), limb salvage (83% vs 62%), and overall survival (77% vs 62%) [39].…”

An Update On Rodent Model Studies In Diabetic Neuropathy: A Brief Communication

“…These murine data support that this network of metabolic impairments activates detrimental feed-forward cycles of local and systemic oxidative stress and dysregulated energy homeostasis with local mitochondrial dysfunction and inflammation, thus resulting in neural injury and DPN. Corroborating this idea, there are some clinical studies showing that dyslipidemiais strongly correlated with DPN [2,87] and that lowering cholesterol, not glycemia, is significantly associated with decreasing lower-extremity amputations among patients with diabetes [2,88].…”