Vascular protection in peripheral artery disease: systematic review and modelling study

Aims: To ascertain the effectiveness of medical therapy for reducing risk in peripheral artery disease (PAD) and to model the potential impact of combining multiple efficacious approaches. Methods and results: 17 electronic databases, reference lists of primary studies, clinical practice guidelines, review articles, trial registries and conference proceedings from cardiology, vascular surgery and atherosclerosis meetings were screened. Eligible studies were randomized trials or meta-analyses of randomized trials of medical therapy for PAD which reported major cardiovascular events (myocardial infarction, stroke and cardiovascular death). Baseline event rates for modelling analyses were derived from published natural history cohorts. Overall, three strategies had persuasive evidence for reducing risk in PAD: antiplatelet agents (pooled RRR 26%, 95% CI 10 to 42), statins (pooled RRR 26%, 95% CI 18 to 33) and angiotensin-converting enzyme inhibitors (individual trial RRR 25%, 95% CI 8 to 39). The estimated cumulative relative risk reduction for all three strategies was 59% (CI 32 to 76). Given a 5-year major cardiovascular event rate of 25%, the corresponding absolute risk reduction and number needed to treat to prevent one event were 15% (CI 8 to 19) and 7 (CI 5 to 12), respectively. Population level analyses suggest that increased uptake of these modalities could prevent more than 200 000 events in patients with PAD each year. Conclusion: The use of multiple efficacious strategies has the potential to substantially reduce the cardiovascular burden of PAD. However, these data should be regarded as hypothetical, since they are based on mathematical modelling rather than factorial randomized trials.