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Tackling Elevated Risk in PAD: Focus on Antithrombotic and Lipid Therapy for PAD

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The PAD population is at increased risk of major adverse cardiovascular events (MACE) and major adverse limb events (MALE). Risk factor modification, symptom control, antithrombotic, and lipid therapies are the mainstays of PAD medical therapy. Recent data has challenged prior recommendations regarding the optimal secondary prevention strategies in PAD.

Purpose of Review

To review clinical evidence from large randomized controlled trials showing the benefit of antithrombotic and lipid therapy in the PAD population.

Recent Findings

The COMPASS trial challenged prior recommendations regarding anticoagulation in PAD. Among the PAD subgroup, rivaroxaban 2.5 mg plus aspirin reduced MACE (HR 0.72, 95% CI 0.57–0.90, p = 0.0047), MALE (HR 0.54, 95% CI 0.35–0.82, p = 0.0037), and major amputation (HR 0.30, 95% CI 0.11–0.80, p = 0.011) compared with aspirin monotherapy. The THEMIS trial showed a 55% risk reduction for MALE with ticagrelor DAPT compared with aspirin monotherapy (HR 0.45, 95% CI 0.23–0.86). The FOURIER trial revealed that lowering LDL cholesterol below current targets with a PCSK9 inhibitor reduced MACE (HR 0.73, 95% CI 0.59–0.91, p = 0.0040) and MALE (HR 0.43, 95% CI 0.19–0.99, p = 0.042) in subjects with symptomatic PAD.


Recent high-quality evidence shows the benefit of antiplatelet therapy, anticoagulation therapy, and lipid therapy in reducing MACE and MALE in PAD. Despite these findings, implementation remains a challenge and focus should now shift towards adopting evidence-based recommendations in clinical practice.

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Correspondence to Nicholas Govsyeyev.

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Conflict of Interest

Nicholas Govsyeyev has nothing to disclose.

Mark R. Nehler reports receiving salary support from CPC Clinical Research.

William R. Hiatt reports receiving clinical trial research grants to CPC Clinical Research from: NIH, Bayer, Janssen, and Amgen.

Marc P. Bonaca reports receiving research grants and personal fees from Amgen, AstraZeneca, Bayer, Merck, NovoNordisk, Pfizer, and Sanofi. He also reports receiving additional grants from Regeneron and personal fees from Janssen.

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Govsyeyev, N., Nehler, M.R., Hiatt, W.R. et al. Tackling Elevated Risk in PAD: Focus on Antithrombotic and Lipid Therapy for PAD. Curr Cardiol Rep 22, 13 (2020).

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  • Peripheral artery disease
  • Antithrombotic therapy
  • Antiplatelet therapy
  • Anticoagulation therapy
  • Lipid therapy
  • Implementation