In a significant study published in Circulation by our long-time SALSAmigos Shipra Arya (Stanford), Luke Brewster (Emory) and Phil Goodney (Dartmouth) data strongly suggest that high-intensity statins may reduce risk for amputation (33% reduction) and survival in PAD patients (26% reduction).
Background—Statin dose guidelines for Peripheral Artery Disease (PAD) patients 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 incident PAD patients (2003-2014) in the national Veterans Affairs data. Highest statin intensity exposure [high intensity vs low- moderate intensity vs antiplatelet therapy but no statin use (AP only)] was determined within one 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 (PS) matched analysis as well as sensitivity and subgroup analyses to reduce confounding.
Results—In 155,647 patients with incident PAD, more than a quarter (28%) were not on statin. Use of high intensity statins was lowest in patients with PAD only (6.4%) as compared to comorbid coronary/carotid disease (18.4%). Incident amputation and mortality risk declined significantly with any statin use compared to AP only group. In adjusted Cox models, the high intensity statin users were associated with lower amputation risk and mortality as compared to AP only users [HR 0.67; 95% CI (0.61, 0.74) and HR 0.74; 95% CI (0.70, 0.77), respectively]. Low-moderate intensity statins also had significant reductions in risk of amputation and mortality [HR amputation 0.81 (0.75, 0.86), HR death 0.83 (0.81, 0.86)] as compared to no statins (AP 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 PS matched, sensitivity and subgroup analyses.
Conclusions—Statins, especially high intensity formulations, are underutilized in PAD patients. This is the first population based study to show that high intensity statin use at time of PAD diagnosis is associated with a significant reduction in limb loss and mortality compared to low-moderate intensity statin users as well as patients treated only with antiplatelet medications but not with statins.