Lipid-lowering for peripheral arterial disease of the lower limb

Background Lipid-lowering therapy is recommended for secondary prevention in people with coronary artery disease. It may also reduce cardiovascular events and/or local disease progression in people with lower limb peripheral arterial disease ( PAD). Objectives To assess the effects of lipid-lowering therapy on all-cause mortality, cardiovascular events and local disease progression in patients with PAD of the lower limb. Search strategy The authors searched The Cochrane Peripheral Vascular Diseases Group's Specialised Register ( last searched February 2007) and the Cochrane Central Register of Controlled Trials ( CENTRAL) ( last searched Issue 2, 2007) for publications describing randomised controlled trials of lipid-lowering therapy in peripheral arterial disease of the lower limb. Selection criteria Randomised controlled trials of lipid-lowering therapy in patients with PAD of the lower limb. Data collection and analysis Three authors independently assessed trial quality and extracted data. Main results Eighteen trials were included, involving a total of 10,049 participants. Trials differed considerably in their inclusion criteria, outcomes measured, and type of lipid- lowering therapy used. Only one trial ( PQRST) reported a detrimental effect of active treatment on blood lipid/lipoprotein levels. The pooled results from all eligible trials indicated that lipid-lowering therapy had no statistically significant effect on overall mortality ( Odds Ratio ( OR) 0.86; 95% Confidence Interval ( CI) 0.49 to 1.50) or on total cardiovascular events ( OR 0.8; 95% CI 0.59 to 1.09). However, subgroup analysis which excluded PQRST showed that lipid- lowering therapy significantly reduced the risk of total cardiovascular events ( OR 0.74; CI 0.55 to 0.98). This was primarily due to a positive effect on total coronary events ( OR 0.76; 95% CI 0.67 to 0.87). Greatest evidence of effectiveness came from the use of simvastatin in people with a blood cholesterol >= 3.5 mmol/litre ( HPS). Pooling of the results from several small trials on a range of different lipid- lowering agents indicated an improvement in total walking distance ( Weighted Mean Difference ( WMD) 152 m; 95% CI 32.11 to 271.88) and pain-free walking distance ( WMD 89.76 m; 95% CI 30.05 to 149.47) but no significant impact on ankle brachial index ( WMD 0.04; 95% CI -0.01 to 0.09). Authors' conclusions Lipid-lowering therapy is effective in reducing cardiovascular mortality and morbidity in people with PAD. It may also improve local symptoms. Until further evidence on the relative effectiveness of different lipid-lowering agents is available, use of a statin in people with PAD and a blood cholesterol level >= 3.5 mmol/litre is most indicated.