Defining Optimal Medical Therapy for CLTI in 2026
Beth Israel Deaconess Medical Center, Boston, Massachusetts
On Friday morning at the Amputation Prevention Symposium, Eric A. Secemsky, MD, MSc, RPVI, FACC, FAHA, FSCAI, FSVM, presented a review of the evidence supporting contemporary medical management for patients with peripheral artery disease (PAD) and chronic limb-threatening ischemia (CLTI), emphasizing that pharmacologic therapy remains an essential pillar of reducing cardiovascular events, preserving limbs, and improving long-term survival.
Dr Secemsky opened by highlighting a persistent challenge in vascular medicine: despite the growing prevalence of PAD worldwide, patients continue to receive less aggressive medical therapy than those with coronary artery disease. Although awareness of PAD has improved, treatment gaps remain in hypertension management, lipid-lowering therapy, and antiplatelet use, contributing to preventable cardiovascular morbidity and mortality. He noted that more than 230 million people worldwide are living with PAD, with prevalence continuing to rise alongside an aging population and increasing healthcare costs.
Drawing from the latest evidence and the 2024 Circulation scientific statement, Dr Secemsky outlined a comprehensive treatment strategy that includes antiplatelet therapy with aspirin or clopidogrel, low-dose rivaroxaban for appropriate patients, high-intensity statin therapy, ACE inhibitor or ARB therapy for hypertension, smoking cessation, and cilostazol for eligible symptomatic patients without heart failure. This multidimensional approach reflects the evolution of PAD management from isolated symptom control to comprehensive vascular risk reduction.
The session reviewed decades of evidence supporting antiplatelet therapy while acknowledging its limitations. Historical trials established aspirin as a foundation of treatment, but Dr Secemsky emphasized that subsequent studies demonstrated meaningful advantages with clopidogrel in patients with symptomatic PAD. Findings from the CAPRIE trial showed improved protection against ischemic stroke, myocardial infarction, and vascular death, along with lower rates of major bleeding compared with higher-dose aspirin, reinforcing clopidogrel's important role in contemporary practice.
One portion of the presentation focused on dual pathway inhibition with low-dose rivaroxaban. Reviewing data from the COMPASS and VOYAGER PAD trials, Dr Secemsky demonstrated how combining rivaroxaban 2.5 mg twice daily with aspirin reduces major adverse cardiovascular events and major adverse limb events while providing an overall net clinical benefit despite an increase in major bleeding. He also highlighted newer subgroup analyses showing substantial reductions in repeat limb revascularization among patients with CLTI, particularly those undergoing endovascular intervention, underscoring the growing role of intensified antithrombotic therapy in high-risk limb salvage patients.
Beyond antithrombotic therapy, the presentation reinforced the importance of aggressive cardiovascular risk factor modification. High-potency statins were associated with reductions in mortality, major cardiovascular events, and lower extremity amputations, while ACE inhibitor and ARB therapy demonstrated favorable outcomes in patients with CLTI. Smoking cessation remained one of the most powerful modifiable interventions discussed, with evidence linking continued tobacco use to impaired wound healing and worse limb outcomes. Together, these therapies illustrate that successful limb preservation depends as much on medical optimization as on technical procedural success.
Dr Secemsky concluded by addressing the evolving role of PAD screening. Emerging evidence from large screening initiatives and population-based studies suggests that identifying PAD earlier may improve opportunities for cardiovascular risk reduction and timely intervention before patients progress to CLTI. As screening strategies continue to mature, earlier diagnosis combined with aggressive implementation of evidence-based medical therapy may help reduce the substantial burden of amputations and cardiovascular complications associated with advanced PAD.
