In adults with type 2 diabetes and peripheral artery disease, statin use was associated with a 25% lower rate of lower-extremity amputations and a 22% risk reduction in cardiovascular mortality when compared with no statin use, according to findings from a population-based study.
“Although there is evidence supporting its beneficial effects on functional reserve and major [CV] events, few studies address the protective effect of statins in terms of the risk for amputation,” Chien-Yi Hsu, MD, of the Institute of Clinical Medicine at National Yang-Ming University in Taipei, Taiwan, and colleagues wrote in the study background. “[A] limited amount of clinical data support the advantage of statins over other lipid-lowering agents on [peripheral artery disease] outcome. … Because many [diabetes] patients with [peripheral artery disease] will die before the initial amputation, this issue has not been fully clarified.”
In an observational cohort study, Hsu and colleagues analyzed data from 69,332 adults with diabetes and peripheral artery disease (PAD) between 2000 and 2011 with 5 years of available data, identified from the National Health Insurance Research Database and the Longitudinal Cohort of Diabetes Patients (mean age, 63 years; 49% men). Patients were stratified by three categories: statin users (n = 11,409); nonstatin lipid-lowering agent users (n = 4,430) and nonusers (n = 53,493). Patients using a combination of statin therapy and other lipid-lowering agents were excluded. Primary outcome was lower-extremity amputation; secondary outcomes included in-hospital CV death and all-cause mortality. Researchers used Cox regression models to calculate HRs for the risk outcomes of the three groups, as well as competing-risk regression using Fine and Gray’s proportional hazards model due to the high mortality rate among patients with diabetes and PAD.
Within the cohort, 73.6% of patients had hypertension; 44.9% had coronary artery disease; 30.8% had cerebrovascular disease; 19% has chronic kidney disease; and 14.6% had heart failure.
During a mean 5.7 years of follow-up, rates of lower-extremity amputation and total lower-extremity amputation were lower in the statin-user group vs. nonusers (2.29 vs. 3.57 per 1,000 person-years; 6.24 vs. 8.72 per 1,000 person-years, respectively), as were combined rates of in-hospital CV death and all-cause mortality (24.38 vs. 38.63 per 1,000 person-years). Compared with nonusers, statin use was associated with a lower risk for lower-extremity amputation (adjusted HR = 0.75; 95% CI, 0.62-0.9). The reduction in risk was even greater for total lower-extremity amputation when comparing statin users with nonusers (adjusted HR = 0.58; 95% CI, 0.36-0.93), according to the researchers. The reduction in risk persisted for lower-extremity amputation when calculating death as a competing risk, but risk was attenuated for total lower-extremity amputation.
Researchers observed no reduction in amputation risk for patients using nonstatin lipid-lowering agents, although these patients, as well as statin users, experienced lower risk for in-hospital CV death and all-cause mortality.
“The salutary property of statin might be partially derived from its pleiotropic effects, such as anti-inflammatory and anti-atherogenic activities, beyond its influence on cholesterol lowering,” the researchers wrote. “Since a randomized, placebo-controlled clinical trial would be unethical given the known beneficial effects of statins on [CV] outcomes, using data from a large, real-world, longitudinal cohort with properly conducted statistical analyses could provide valuable epidemiologic evidence to clarify the potential protective effects of statins on limb outcomes.” – by Regina Schaffer