Invited commentary

Abstract

Current guidelines give a class I recommendation to lower low-density lipoprotein (LDL) cholesterol levels below 100 mg/dL in all patients with peripheral artery disease (PAD) and a class IIa recommendation to lower the LDL cholesterol level below 70 mg/dL in patients who are at “very high risk of ischemic events.”1Hirsch A.T. Haskal Z.J. Hertzer N.R. et al.ACC/AHA 2005 guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic).J Am Coll Cardiol. 2006; 47: 1239-1312Abstract Full Text Full Text PDF PubMed Scopus (1068) Google Scholar High-risk PAD would be defined as more than one vascular bed involved—eg, a clinical history of concomitant coronary or cerebral vascular disease. The primary evidence for these recommendations comes from the original publication of the Heart Protection Study that evaluated the benefits of simvastatin in over 20,000 high-risk patients.2MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial.Lancet. 2002; 360: 7-22Abstract Full Text Full Text PDF PubMed Scopus (7641) Google Scholar There were 6748 patients with PAD reported in the original publication, and these patients had a reduction in fatal and nonfatal cardiovascular events with simvastatin similar to that in patients with other forms of atherosclerosis. A recent meta-analysis of statin therapy in a broad population of high-risk patients demonstrated that there was a consistent benefit in reduction of risk of cardiovascular events across a wide population of patients and a wide range of baseline LDL cholesterol levels.3Baigent C. Keech A. Kearney P.M. et al.Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins.Lancet. 2005; 366: 1267-1278Abstract Full Text Full Text PDF PubMed Scopus (5745) Google Scholar Thus there is a broad consensus to treat all patients at risk with statin drugs, regardless of their baseline cholesterol level. The publication of the Heart Protection Study Collaborative Group in the Journal of Vascular Surgery focuses on the benefits of statin therapy specifically in the PAD population. The major new finding was a significant reduction in noncoronary revascularizations. Confirmatory findings were the consistency of the benefit across all populations studied (including patients with PAD who had no pre-existing coronary artery disease) and benefit regardless of baseline LDL cholesterol level. There was no benefit of the statin in preventing amputations, perhaps reflecting the end-stage pathophysiology of patients who suffer limb loss. The message is clear. All patients with PAD are at high risk and meet criteria for statin therapy. The benefit of statin therapy is primarily systemic (prevention of major cardiovascular events) but also local (reduction of the need for revascularization). Randomized trial of the effects of cholesterol-lowering with simvastatin on peripheral vascular and other major vascular outcomes in 20,536 people with peripheral arterial disease and other high-risk conditionsJournal of Vascular SurgeryVol. 45Issue 4PreviewThe Heart Protection Study (HPS) provides an opportunity to assess directly the effects of cholesterol-lowering therapy on major vascular events (defined as myocardial infarction, coronary death, stroke, or revascularization) in patients with peripheral arterial disease (PAD). In addition, the effects on peripheral vascular events (ie, non-coronary revascularization, aneurysm repairs, major amputations or PAD deaths) can be assessed. Full-Text PDF Open Archive