Personalizing Post Surgical Thromboprophylaxis for Elderly Patients with Peripheral Artery Disease

Peripheral artery disease (PAD) is increasingly prevalent with advancing age and often necessitates revascularization with endovascular surgery to improve limb perfusion. However, thrombosis of endovascular interventions occurs in approximately one in five patients within 6 months post-surgery and is the leading cause of amputation in older adults (≥65 years). Prognosis after amputation is poor, with up to 50% of older patients dying within a year. Post-menopausal women face double the risk of arterial thrombosis compared to men and are more likely to die post amputation. Therefore, preventing arterial thrombosis is a critical surgical need in older patients after endovascular revascularization, especially for postmenopausal women. The current thromboprophylaxis standard of care (SOC) for preventing arterial thrombosis is 1) dual antiplatelet therapy (DAPT) with aspirin and clopidogrel or 2) low-dose rivaroxaban (an anticoagulant) with aspirin. While this “one size fits all” approach is intended to reduce the risk of major lower extremity thrombosis, 20% of patients still experience post-surgical thrombosis and this high failure rate of the current SOC underscores the urgency of developing novel strategies to prevent arterial thrombosis, thereby reducing amputations in older patients. To address this critical gap, our team has developed and piloted the Thromboprophylaxis for Arterial Revascularization to Guide Elderly Therapy (TARGET) protocol, which personalizes thromboprophylaxis based on individualized coagulation profiles. An individual’s coagulation profile is evaluated through a widely available point of care (POC) assay called thromboelastography with platelet mapping (TEG-PM). TARGET is a novel approach that allows clinicians to use objective coagulation data to personalize the administration of commonly used thromboprophylaxis medications thereby mitigating thrombosis without increasing bleeding. The goal of this R01 proposal is to conduct a multicenter, randomized controlled trial (RCT) to evaluate efficacy of the TARGET protocol in reducing thrombosis post lower extremity revascularization. Our central hypothesis is that the TARGET protocol will significantly reduce thrombosis rates compared to the SOC, and that women will be less responsive to DAPT due to differences in their platelet P2Y12 signaling pathway. Our aims are to 1) Evaluate the effectiveness of the personalized TARGET protocol to thromboprophylaxis in reducing thrombosis rates compared to the SOC, and 2) Identify the mechanisms contributing to sex-specific differences in platelet response to antiplatelet medications. Project Number: 1R01AG094610-01A1 | Fiscal Year: 2026 | NIH Institute/Center: National Institute on Aging (NIA) | Principal Investigator: Anahita Dua | Institution: MASSACHUSETTS GENERAL HOSPITAL, BOSTON, MA | Award Amount: $802,936 | Activity Code: R01 | Study Section: Special Emphasis Panel[ZRG1 RCCS-Q (02)] View on NIH RePORTER: https://reporter.nih.gov/project-details/11364022