Post-Operative Biomarker-Guided Precision Medicine for Cardiovascular Risk Reduction

/Abstract Non-cardiac surgery (NCS) is a major iatrogenic stressor that can unmask subclinical cardiovascular (CV) disease. Biomarker surveillance in the perioperative period of NCS identifies patients with unrecognized or subclinical CV disease at risk of long-term adverse CV outcomes. Myocardial injury after NCS (MINS), defined by a post-operative elevated troponin, with or without ischemic symptoms, is associated with short and long- term CV complications and mortality. Unfortunately, treatment pathways to reduce long term CV risks after non-cardiac surgery have not been defined in patients with MINS, limiting enthusiasm for biomarker screening. The long-term goal of the proposed research is to carry out an international multisite randomized clinical trial to evaluate perioperative biomarker-based precision care with targeted long-term use of a low-dose direct oral anticoagulant and high-intensity statin therapy to improve CV outcomes in patients with MINS. The successful design and execution of the future clinical trial is dependent on identifying study sites that are high volume surgical centers with sufficient frequency of post-operative troponin surveillance, refinement of study entry criteria and study interventions that will promote robust recruitment and study retention based on both clinician and participant preferences, and demonstration of study feasibility through a pilot randomized controlled trial. The current application proposes three objectives; for Objective 1, site surveys will be designed and distributed to acquire data on the number of potential participants with MINS at potential study sites, approaches to perioperative biomarker surveillance, current post-operative management of MINS, and potential barriers to enrollment. For Objective 2, questionnaires based on clinical scenarios will be designed and distributed to characterize clinician equipoise for treatment based on post-operative cardiac biomarkers overall and according to demographics, biomarker thresholds, clinical risk factors, surgical subtypes, and bleeding risks. For Objective 3, a pilot randomized trial of low-dose direct oral anticoagulant and high-intensity statin versus usual care in 50 patients with MINS will be conducted to determine enrollment feasibility and adherence to therapy at 2 months. A mixed methods approach that integrates qualitative data collected from patient interviews and quantitative methods based on Best-Worst scaling surveys and discrete choice experiments will be implemented to determine patient preferences for therapy after non-cardiac surgery (based on attributes including CV benefit, bleeding risks, convenience and costs). The data obtained for each of the objectives will be used to assess feasibility and optimize study design (entry criteria, study endpoints, sample size calculation, site selection) and recruitment strategies for the future randomized clinical trial studying biomarker-based care in post-operative patients at elevated CV risk. Project Number: 1R34HL173301-01A1 | Fiscal Year: 2025 | NIH Institute/Center: National Heart Lung and Blood Institute (NHLBI) | Principal Investigator: Nathaniel Smilowitz | Institution: NEW YORK UNIVERSITY SCHOOL OF MEDICINE, NEW YORK, NY | Award Amount: $392,037 | Activity Code: R34 | Study Section: NHLBI Single-Site and Pilot Clinical Trials Study Section[SSPT (OA)] View on NIH RePORTER: https://reporter.nih.gov/project-details/1R34HL17330101A1