Findings reported in the Journal of Clinical Endocrinology and Metabolism linked statin therapy with reduced risk for lower limb amputation, in-hospital cardiovascular death, and all-cause mortality in patients with diabetes and peripheral artery disease (PAD).1
Associated with an increased prevalence of PAD — a marker of systemic atherosclerosis2 — diabetes is also linked with an elevated risk for critical ischemia and contralateral leg disease.3,4“When not managed properly, PAD may lead to amputation resulting in disability, hospitalization, and death,” Po-Hsun Huang, MD, PhD, of the Division of Cardiology at Taipei Veterans General Hospital in Taiwan, and colleagues wrote.
Previous results demonstrated benefits of statins on both functional reserve and cardiovascular events in patients with PAD, and guidelines by the American College of Cardiology/American Heart Association and the European Society of Cardiology recommend statin therapy for such individuals.5-8 However, there is limited research investigating whether or not statins reduce the risk of amputation.
“[D]eath is a potential competing risk for amputation. Because many [patients with diabetes] with PAD may die before the initial amputation, this issue has not been fully clarified,” Dr Huang and colleagues noted.
In the present study, the researchers conducted an observational cohort study, analyzing information from a nationwide diabetes database to determine the association between statin use and the rate of lower extremity amputation in high-risk patients with PAD. They examined sociodemographic data and a wide range of clinical variables, including comorbidities and concomitant use of other drugs.
In both treatment groups, the regimen had been initiated in the 90 days following PAD diagnosis. Lower extremity amputation was the main outcome, and in-hospital cardiovascular death and all-cause mortality were the secondary outcomes. Patients receiving a combination of the 2 medications were excluded from the study.
A total of 69,332 adult patients with diabetes and PAD (mean age, 62.6±13 years; 49% men) were divided into 3 groups: 11,409 patients were prescribed statins, 4430 were prescribed non-statin lipid-lowering agents, and 53,493 patients did not take either drug. Hypertension was the most commonly observed comorbid condition, affecting 73.6% of patients. Other comorbidities included coronary artery disease (44.9%), cerebrovascular disease (30.8%), heart failure (14.6%), chronic kidney disease (19%), atrial fibrillation (3.5%), and cancer (11%). Comorbidities were more common in the statin group.
Over a mean follow-up of 5.7 years, statin users demonstrated a reduced risk for amputation(adjusted hazard ratio [aHR] 0.75; 95% CI, 0.62-0.90), in-hospital cardiovascular death (aHR 0.78; 95% CI, 0.69-0.87), and all-cause mortality (aHR 0.73; 95% CI, 0.69-0.77), compared with patients never treated with lipid-lowering agents. Propensity-score matching analysis further supported these results, showing a decreased risk for amputation (HR 0.77; 95% CI, 0.61-0.97) and cardiovascular death (HR 0.78; 95% CI, 0.68-0.89).
The group taking non-statin lipid-lowering agents did not show a significant decrease in amputation risk (aHR 0.95; 95% CI, 0.73-1.23), although they did have a reduced risk for cardiovascular death and mortality.
“These findings suggest that statin therapy not only reduces the risk of adverse cardiovascular events, but also has favorable[ly] effects of limb prognosis in [patients with diabetes] with PAD,” the researchers concluded.