The goal of this clinical trial is to determine whether a personalised blood clot prevention plan is more effective than standard treatment in adults with peripheral artery disease (PAD) who have undergone a procedure to restore blood flow to their legs.

The main questions it aims to answer are:

• Does the personalized plan lower the rate of blood clots in the treated leg one year after the procedure?
• Does the personalized plan lower rates of amputation, repeat procedures, bleeding, and death compared to standard treatment?

Researchers will compare the personalized TARGET plan which uses a blood test to tailor each person's blood clot prevention medication to the standard treatment to see if the personalized approach works better.

Participants will:

• Be randomly assigned to either the personalized TARGET plan or standard treatment after their procedure
• Have blood tests at 1 week and at 1, 3, 6, 9, and 12 months after their procedure
• Have medications adjusted based on blood test results if assigned to the TARGET group

SCIENTIFIC RATIONALE Graft and stent thrombosis occurs in approximately 17% of PAD patients within 6 months of lower extremity revascularization and is the leading driver of amputation and death in this population. Current standard-of-care (SOC) thromboprophylaxis applies a uniform antiplatelet regimen despite well-documented inter-patient variability in platelet reactivity and drug response - up to 60-65% of PAD patients demonstrate resistance to aspirin or clopidogrel. The absence of personalized, objective thromboprophylaxis strategies represents a critical gap in PAD management.

TECHNOLOGY: THROMBOELASTOGRAPHY WITH PLATELET MAPPING (TEG-PM)

TEG-PM is a whole-blood, point-of-care assay providing real-time assessment of a patient's complete coagulation profile. TEG characterizes clot initiation (R time), kinetics (K time, α angle), maximum clot strength (mA), and fibrinolysis (Lysis 30), enabling discrimination between hypo- and hypercoagulable states. Platelet Mapping quantifies platelet inhibition via arachidonic acid (AA) and adenosine diphosphate (ADP) agonist assays, yielding a platelet inhibition percentage that reflects each patient's real-time pharmacodynamic response to antiplatelet therapy. All samples are analyzed on a TEG 6s (Haemonetics®) Hemostasis Analyzer within validated processing windows using citrated and sodium heparin tubes.

PRELIMINARY DATA A prospective observational study of 162 PAD patients identified platelet inhibition as the sole independent predictor of post-revascularization thrombosis. A threshold of 29% identified high thrombotic risk (87% sensitivity, 71% specificity; AUC 0.756), while an upper threshold of 86% identified elevated bleeding risk (71% sensitivity, 87% specificity; AUC 0.84), defining a therapeutic window of 29-86%. A separate analysis of 521 TEG-PM samples from 143 PAD patients confirmed extensive inter-patient variability in platelet inhibition response, supporting the case against uniform treatment strategies.

Pilot implementation in 34 patients produced a thrombosis rate of 3.8% vs. 20% under SOC (p<0.05) with no increase in bleeding. A subsequent prospective comparison of 70 protocol-guided patients against 267 SOC patients demonstrated thrombosis rates of 4.3% vs. 20.6%, with fewer bleeding events in the protocol-guided arm.

THE TARGET PROTOCOL The Thromboprophylaxis for Arterial Revascularization to Guide Elderly Therapy (TARGET) protocol integrates serial TEG-PM assessments into clinical decision-making to maintain platelet inhibition within the 29-86% therapeutic window throughout 12 months. TEG-PM is first performed at 7 days postoperatively. If platelet inhibition falls outside the therapeutic range, the antiplatelet regimen is adjusted per a prespecified escalation/de-escalation algorithm, with repeat testing 7 days after each change. Once the target range is achieved, monitoring continues at 1, 3, 6, 9, and 12 months with adjustments made as needed. Patients refractory to stepwise adjustments are referred to hematology once for further evaluation and remain enrolled on their last recommended regimen. All patients who receive clopidogrel for at least 7 days undergo VerifyNow P2Y12 resistance testing at a single timepoint to inform agent selection. Control arm patients receive SOC therapy throughout; TEG-PM is collected for data purposes only with no medication adjustments made.

COAGULATION TESTING SCHEDULE TEG-PM samples are collected at: preoperative baseline, 1 week (7-20 days post-op), 1 month (27-47 days), 3 months (85-105 days), 6 months (180-210 days), 9 months (270-295 days), and 12 months (365-390 days). Unscheduled samples may be collected at the PI's discretion in response to clinical events such as thrombosis, bleeding, or inconclusive results.

Inclusion Criteria:

• Patients with a named arterial extremity injury or named vessel revascularization for atherosclerosis requiring open and/or closed revascularization.
• Patients at the age of 18 or older

Exclusion Criteria:

• Patients who are younger than 18 years old
• Known pregnancy (females of childbearing potential will have a pregnancy test prior to surgery as per standard of care)
• Prisoners, defined as those who have been directly admitted from a correctional facility.
• No atherosclerosis
• Subject has active stomach ulcers
• Subject has severe hepatic impairment
• Subject has a recent history of intracranial hemorrhage. If the patient has a history of cerebral hemorrhage with no new central nervous system disease of >1 year, the study team will consult with the