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Evidence summaries

Lipid-Lowering Pharmacotherapy for Lower Limb Ischaemia

Lipid-lowering therapy reduces cardiovascular morbidity and may reduce mortality in people with peripheral arterial disease. Level of evidence: "A"

Summary

A Cochrane review [Abstract] 1 included 18 studies with a total of 10 049 subjects. The pooled results from all eligible trials indicated that lipid-lowering therapy had no statistically significant effect on overall mortality (OR 0.86, 95% 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 the only study showing a detrimental effect of active treatment on blood lipid/lipoprotein levels, showed that lipid-lowering therapy significantly reduced the risk of total cardiovascular events (OR 0.74, CI 0.55 to 0.98); 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 HASH(0x2fcaf98) 3.5 mmol/litre. Pooling of the results from several small trials on a range of different lipid-lowering agents indicated an improvement in total walking distance (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).

The Heart Protection Study (HPS) 2, included in the Cochrane review 1, randomized 6 748 subjects with PAD and 13 788 other high-risk subjects to receive 40 mg simvastatin daily or matching placebo, yielding an average LDL cholesterol difference of 1.0 mmol/L during a mean of 5 years.In subjects with PAD at study entry, simvastatin reduced the rate of first major vascular event (defined as major coronary events, strokes of any type, and coronary or non-coronary revascularizations) by 22% (95% CI 15 to 29%; p<0.0001), which was similar to that seen among the other high-risk participants (25%, 95% CI 20 to 31%, p<0.0001).

A systematic review 3 included 12 observational cohort studies and 2 randomized trials with a total of 19 368 subjects with PAD. Statin therapy was associated with reduced all-cause mortality (OR 0.60, 95% CI 0.46 to 0.78) and incidence of stroke (OR 0.77, 95% CI 0.67 to 0.89). A trend towards improved cardiovascular mortality (OR 0.62, 95% CI 0.35 to 1.11), myocardial infarction (OR 0.62, 95% CI 0.38 to 1.01), and the composite of death/myocardial infarction/stroke (OR 0.91, 95% CI 0.81 to 1.03), was identified.

    References

    • Aung PP, Maxwell HG, Jepson RG, Price JF, Leng GC. Lipid-lowering for peripheral arterial disease of the lower limb. Cochrane Database Syst Rev 2007 Oct 17;(4):CD000123. [PubMed]
    • Heart Protection Study Collaborative Group. 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 conditions. J Vasc Surg 2007;45(4):645-654; discussion 653-4. [PubMed]
    • Antoniou GA, Fisher RK, Georgiadis GS et al. Statin therapy in lower limb peripheral arterial disease: Systematic review and meta-analysis. Vascul Pharmacol 2014;63(2):79-87. [PubMed]

Primary/Secondary Keywords