Patients with chronic lower extremity artery disease (LEAD) treated with a more vs less intensive antithrombotic therapeutic regimen were found to be at lower risk for limb amputation, stroke, and revascularization, according to a study published in the European Heart Journal-Cardiovascular Pharmacotherapy.

An estimated 202 million people worldwide are thought to have LEAD. In LEAD, atherosclerotic plaque rupture may occur and lead to arterial thrombosis, which requires revascularization (surgical or endovascular). In cases of unsuccessful revascularization, limb amputation may be necessary.

In this systematic review and meta-analysis, studies in which the safety and efficacy of antithrombotic therapies of different intensities were examined in patients with LEAD, were included for review if: ≥200 patients were enrolled; participants were randomly allocated to receive more vs less intensive antithrombotic therapy (ie, more vs less intense single-antiplatelet therapy [SAPT]; or dual-antiplatelet therapy vs SAPT; or dual antithrombotic therapy vs SAPT or oral anticoagulant); and if the patients reported  limb amputation and/or revascularization. In total, 7 randomized studies with a total of 30,447 patients were evaluated. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) protocol was used to summarize the results and score the overall quality of evidence.

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More vs less intense antithrombotic therapy was found to reduce the risk for by 11% (relative risk [RR], 0.89; 95% CI, 0.83 – 0.94) and that of limb amputation by 37% (RR, 0.63, 95% CI, 0.46-0.86; median follow-up, 24 months), and that of stroke by 18% (RR, 0.82; 95% CI, 0.70-0.97). The risks for myocardial infarction, cardiovascular, and all-cause death were comparable in patients treated with a more vs less intensive therapy. Lastly, although the more intense therapies were more effective, they also increased the risk for major bleeding (RR, 1.23; 95% CI, 1.04-1.44).

Limitations of the study include the fact that the analyses were based on aggregate trial- and not patient-level data, and a lack of time-to-event analyses.

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“These findings may foster changes in clinical practice, while encouraging future randomized trials powered specifically on [major adverse limb events] outcomes in [patients with] chronic LEAD,” concluded the study authors.


Savarese G, Reiner MF, Uijl A, D’Amario D, Agewall S, Atar D. Antithrombotic therapy and major adverse limb events in patients with chronic lower extremity arterial disease: systematic review and meta-analysis from the European Society of Cardiology Working Group on Cardiovascular Pharmacotherapy in Collaboration with the European Society of Cardiology Working Group on Aorta and Peripheral Vascular Diseases. Eur Heart J Cardiovasc Pharmacother. 2020 Apr 1;6(2):86-93.