Variations in Antithrombotic Prescriptions and Evaluation of Extended Clopidogrel Therapy After Lower Extremity Revascularization for Peripheral Artery Disease.

Abstract

Objectives: The optimal antithrombotic combination and duration after open surgical or endovascular lower extremity revascularization (LER) in patients with peripheral arterial disease (PAD) lacks consensus. This study examines the variability of antithrombotic prescriptions in a tertiary care center, highlighting challenges in related research. The duration of the various prescriptions was captured and this study focused on studying the impact of duration of clopidogrel therapy on patient outcomes.

Methods: The electronic medical records of patients with PAD undergoing LER were reviewed. All antithrombotic prescriptions after initial LER were abstracted by pharmacists. Demographics and clinical characteristics of patients who received clopidogrel after initial LER were evaluated. Comparison of patients who received extended clopidogrel therapy (> 12 months) compared to limited clopidogrel therapy (≤ 12 months) was performed. Perioperative and long-term outcomes were compared and analysis focused on Major Adverse Limb Events (MALE), Major Adverse Cardiac Events (MACE), and mortality.

Results: A total of 1,954 patients received 17 different perioperative antithrombotic combinations and 101 combinations over long-term follow up. Clopidogrel was the most commonly used medication in 69.8% (N=1,363). Among patients treated with clopidogrel after LER, 69.5% (N=947) received extended therapy (>12 months). Patients who received extended clopidogrel therapy were more likely to have had a prior endovascular procedure (21.8% vs 15.2%, P=0.005), while those who received limited therapy (≤12 months) were older (72 vs 69, P<0.001) and more likely to have congestive heart failure (21% vs 14%, P=0.001) and chronic renal insufficiency (22.2% vs 15.6%, P<0.004). Patients in the extended therapy group were more likely to be treated for claudication (57.5% vs 46.1%, P<0.001) compared to patients with limited therapy but there was no difference in revascularization strategies. Kaplan-Meier curves showed significantly higher overall survival, MALE-free survival, and MACE-free survival in patients with extended clopidogrel therapy without difference in freedom from MALE or MACE. Cox regression demonstrated independent association of limited clopidogrel therapy with mortality (HR=1.93[1.6-2.31]), mortality or MALE (HR=1.32[1.14-1.53]), and mortality or MACE (HR=1.39[1.2-1.62]). The duration of clopidogrel therapy was not associated with bleeding.

Conclusion: The number of unique prescription combinations found in this study highlights real-world variations in antithrombotic therapy after revascularization for patients with PAD. Extended clopidogrel therapy was associated with improved survival compared to limited therapy in this analysis without increase in bleeding. Observational studies on antithrombotic therapy are limited by extensive variations and factors affecting prescription patterns that can only be reconciled with prospective randomized trials.