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
Presented at the Sixtieth Annual Meeting of the Society for Vascular Surgery, Philadelphia, Pa, June 1-4, 2006.
Received 30 May 2006; accepted 18 December 2006.
Objectives
The 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.
Methods
6748 UK adults with PAD and 13,788 other high-risk participants were randomly allocated to receive 40 mg simvastatin daily or matching placebo, yielding an average LDL cholesterol difference of 1.0 mmol/L (39 mg/dL) during a mean of 5 years.
Results
For participants with PAD, allocation to simvastatin was associated with a highly significant 22% (95% CI 15-29) relative reduction in the rate of first major vascular event following randomisation (895 [26.4%] simvastatin-allocated vs 1101 [32.7%] placebo-allocated; P < .0001), which was similar to that seen among the other high-risk participants. The absolute reduction in first major vascular event was 63 (SE 11) per 1000 patients with PAD and 50 (SE 7) per 1000 without pre-existing PAD. Overall, among all participants, there was a 16% (5-25) relative reduction in the rate of first peripheral vascular event following randomisation (479 [4.7%] simvastatin vs 561 [5.5%] placebo), largely irrespective of baseline LDL cholesterol and other factors. This effect chiefly reflects a 20% (8-31) relative reduction in non-coronary revascularization procedures (334 [3.3%] vs 415 [4.0%]; P = .002).
Conclusion
HPS demonstrates the benefits of cholesterol-lowering statin therapy in patients with PAD, regardless of their presenting cholesterol levels and other presenting features. Allocation to 40 mg simvastatin daily reduces the rate of first major vascular events by about one-quarter, and that of peripheral vascular events by about one-sixth, with large absolute benefits seen in participants with PAD because of their high vascular risk. Consequently, statin therapy should be considered routinely for all patients with PAD.
Correspondence to: Heart Protection Study, Clinical Trial Service Unit and Epidemiological Studies Unit, Richard Doll Building, University of Oxford, Old Road Campus, Roosevelt Dr, Oxford OX3 7LF, UK.
The study was funded by the UK Medical Research Council (MRC), the British Heart Foundation (BHF), Merck & Co (manufacturers of simvastatin), and Roche Vitamins Ltd (manufacturers of the vitamins).
Competition of interest: The Clinical Trial Service Unit has a staff policy of not accepting honoraria or other payments from the pharmaceutical industry, except for the reimbursement of costs to participate in scientific meetings. Members of the writing committee have, therefore, only had such costs reimbursed.
CME article
1 Writing and other Committees are listed in the Appendix, and collaborators and participating hospitals are listed in reference 17.
ABSTRACT