Tailored Treatment Strategies for Patients with Chronic Limb Threatening Ischemia - PROJECT SUMMARY Consistent with the research priorities of the National Heart, Lung, Blood Institute, this proposed study will investigate optimal treatment algorithms for patients with chronic limb threatening ischemia (CLTI). CLTI is the most severe, debilitating, and progressive form of peripheral artery disease. Successful treatment requires ongoing combinations medical, wound/podiatric, and endovascular or surgical vascular care. Despite the availability of multiple life- and limb-preserving treatments, success in improving health outcomes of patients afflicted with CLTI has been limited. Several patient factors influence the effectiveness of treatments over time: socioeconomic conditions, adherence to best medical therapy, degree of success with revascularization, and ability to attend postoperative vascular surveillance appointments. A lack of understanding of how these clinical and social factors affect CLTI treatment sequences and impact CLTI-free survival is a critical barrier to saving lives and limbs. The recently completed NHLBI-sponsored BEST-CLI randomized controlled trial with 1830 adult participants determined that surgical vein bypass is the most effective initial revascularization approach for patients with CLTI, but almost 10% required major vascular re- intervention, 10% underwent major limb amputation, and 33% died within two years. Our proposed research will use advanced analytics and machine learning to leverage the BEST-CLI trial data to identify the patient characteristics that associate with different disease trajectories and treatment patterns after the initial revascularization (Aim 1). Aim 2 will measure the effect of partial adherence to clinical follow-up visits on these clinical trajectories and CLTI-free survival. The identified patterns will define treatment tailoring opportunities- key decision points at which treatment decisions can be customized to individuals based on their unique clinical features. To address the non-clinical factors that influence treatment adherence and CLTI outcomes, Aim 3 is a prospective qualitative study, including semi-structured interviews and a user- centered design approach called journey mapping, that will identify facilitators, gaps and unmet needs that impact patients’ ability to adhere. This will inform where additional support should be integrated to make individualized, optimal treatment plans accessible to all patients. Our final output will include individually tailored, socially supportive treatment plans that improve the health of patients with CLTI. In the future, these candidate treatment algorithms will be tested with sequential multiple assignment randomized trials (SMARTs) to realize the goal of bringing precision medicine (“right treatment, right person, right time”) to CLTI care.
