PCSK9 INHIBITORS IN PERIPHERAL ARTERY DISEASE: REVIEW OF EFFICACY, SAFETY, AND OUTCOMES

Abstract

Therapeutic Area

Peripheral Artery Disease

Background

Peripheral artery disease (PAD) is a debilitating condition characterized by atherosclerosis in the peripheral arteries, affecting approximately 200 million people worldwide. Current treatment options for PAD, such as statins, have limitations in terms of efficacy and tolerability. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have shown promise in reducing cardiovascular events in hypercholesterolemic patients. This review focuses on the efficacy, safety, and clinical outcomes of PCSK9 inhibitors in PAD based on recent trials and literature.

Methods

A comprehensive literature search was conducted using PubMed to identify relevant trials and studies evaluating PCSK9 inhibitors in PAD patients. Key trials including FOURIER and ODYSSEY were analyzed for efficacy in reducing LDL cholesterol levels and cardiovascular events, including myocardial infarction, stroke, coronary revascularization, and major adverse limb events. Safety data was compiled from multiple trials. Cost-effectiveness studies were also reviewed.

Results

The FOURIER trial demonstrated that evolocumab significantly reduced LDL cholesterol by 59% (p<0.001) and the risk of cardiovascular events (HR 0.85; 95% CI, 0.79 to 0.92; p<0.001) in PAD patients at 48 weeks. The ODYSSEY trial showed similar LDL reductions of 55% at 4 months and 63% at 48 months with alirocumab. Injection site reactions were the most common adverse event in safety evaluations (evolocumab 2.1% vs placebo 1.6%). Despite high costs (incremental cost-effectiveness ratios >$500,000 per QALY in some analyses), PCSK9 inhibitors may be cost-effective in specific high-risk populations.

Conclusions

PCSK9 inhibitors demonstrate significant efficacy in lowering LDL cholesterol and reducing cardiovascular events in PAD patients, with a favorable safety profile. However, cost remains a barrier to widespread utilization. Current PAD treatment guidelines do not yet incorporate PCSK9 inhibitors. Further research is needed on long-term outcomes, cost-effectiveness, and the role of PCSK9 inhibitors in the context of current PAD management. PCSK9 inhibitors represent a promising therapeutic option for select high-risk PAD patients not at goal with statins alone.