Statin Therapy and Long-term Adverse Limb Outcomes in Patients With Peripheral Artery Disease

Insights From the REACH Registry

Dharam J. Kumbhani; Ph. Gabriel Steg; Christopher P. Cannon; Kim A. Eagle; Sidney C. Smith Jr; Shinya Goto; E. Magnus Ohman; Yedid Elbez; Piyamitr Sritara; Iris Baumgartner; Subhash Banerjee; Mark A. Creager; Deepak L. Bhatt


Eur Heart J. 2014;35(41):2864-2872. 

In This Article

Abstract and Introduction


Aims Due to a high burden of systemic cardiovascular events, current guidelines recommend the use of statins in all patients with peripheral artery disease (PAD). We sought to study the impact of statin use on limb prognosis in patients with symptomatic PAD enrolled in the international REACH registry.

Methods Statin use was assessed at study enrolment, as well as a time-varying covariate. Rates of the primary adverse limb outcome (worsening claudication/new episode of critical limb ischaemia, new percutaneous/surgical revascularization, or amputation) at 4 years and the composite of cardiovascular death/myocardial infarction/stroke were compared among statin users vs. non-users.

Results A total of 5861 patients with symptomatic PAD were included. Statin use at baseline was 62.2%. Patients who were on statins had a significantly lower risk of the primary adverse limb outcome at 4 years when compared with those who were not taking statins [22.0 vs. 26.2%; hazard ratio (HR), 0.82; 95% confidence interval (CI), 0.72–0.92; P = 0.0013]. Results were similar when statin use was considered as a time-dependent variable (P = 0.018) and on propensity analysis (P < 0.0001). The composite of cardiovascular death/myocardial infarction/stroke was similarly reduced (HR, 0.83; 95% CI, 0.73–0.96; P = 0.01).

Conclusion Among patients with PAD in the REACH registry, statin use was associated with an ~18% lower rate of adverse limb outcomes, including worsening symptoms, peripheral revascularization, and ischaemic amputations. These findings suggest that statin therapy not only reduces the risk of adverse cardiovascular events, but also favourably affects limb prognosis in patients with PAD.


Lower extremity peripheral artery disease (PAD) affects nearly one-fifth of all adults older than 55 years of age, with increased prevalence in high-risk subgroups such as those with diabetes, renal insufficiency, and smoking.[1–4] Patients with PAD have high rates of systemic event rates such as myocardial infarction, stroke, and death, with higher rates in symptomatic patients.[5–12] These can be as high as five-fold for cardiovascular mortality and three-fold for all-cause mortality after adjustment for known Framingham risk factors.[5] In a pre-specified subgroup analysis of the Heart Protection Study (HPS) in patients with known PAD, simvastatin use was associated with a 20–25% reduction in major adverse cardiovascular events when compared with placebo.[8] Accordingly, current guidelines for secondary prevention and risk reduction in patients with PAD strongly recommend lipid-lowering therapy with a statin to achieve a goal low-density lipoprotein (LDL) level of ≤100 mg/dL in low-risk patients and ≤70 mg/dL in high-risk patients.[13,14] However, patients with PAD also have a high incidence of adverse limb outcomes. This can be as a high as a 25% annual risk of limb amputation in patients with advanced disease.[15] The association between statin use and limb outcomes in patients with PAD is unclear.

Since a randomized controlled trial would be unethical given the known salutary effects of statins on cardiovascular outcomes, we decided to investigate this hypothesis further in the large international Reduction of Atherothrombosis for Continued Health (REACH) Registry.