PROJECT SUMMARY Current care patterns for the 7 million patients visiting Emergency Departments (EDs) in the United States with chest pain are heterogenous and not sustainable from a healthcare quality or economic perspective. Chest pain is the second most common cause of ED visits and most common reason for short-stay hospitalizations. During these hospitalizations patients undergo in-depth evaluations (stress testing, computed tomography coronary angiography, or invasive angiography), but ultimately <10% are diagnosed with acute coronary syndrome (ACS). These evaluations cost $3 billion annually and strain health system resources without clear evidence of improved health outcomes or patient experience. Our preliminary data suggest that moderate risk patients (35% of patients with chest pain) can be safely managed as outpatients using a cardiovascular ambulatory rapid evaluation (CARE) strategy as an alternative to hospitalization. In the CARE strategy, patients are discharged from the ED and receive outpatient clinic follow-up within 72 hours focused on medical management for cardiovascular risk factors (e.g., hypertension, diabetes) and determining whether further cardiac testing is needed. This strategy aims to enhance patient-centered outcomes while safely and equitably decreasing hospital resource utilization. However, equipoise exists between outpatient and hospitalization strategies for moderate risk patients. There is a paucity of prospective data evaluating the efficacy and patient-centeredness of outpatient chest pain evaluation strategies in moderate risk patients. Thus, it is unclear whether use of an outpatient chest pain management strategy (CARE) will safely reduce healthcare utilization and be preferred by patients compared to a traditional hospitalization strategy. To address this key evidence gap, we propose the first prospective multisite randomized trial testing outpatient vs hospitalization strategies in moderate risk patients. Our experienced research team will randomize 502 patients 1:1 to the CARE or hospitalization management arms at three ED sites with a history of high recruitment rates and productive collaborations in cardiovascular clinical trials. The primary outcome will be hospital-free days (HFD) over a 30-day period. Patient-centered outcomes, such as patient satisfaction and experience and out-of-pocket cost will be assessed at 30-days. Additional endpoints include HFD over 1-year, 30-day and 1-year cardiovascular HFD, rates of noninvasive and invasive cardiac testing, cardiovascular rehospitalizations, and cardiovascular repeat ED visits. Patients will be monitored for safety: the composite of cardiovascular death, myocardial infarction, and unplanned coronary revascularization at 30-days. This novel trial addresses a key evidence gap by providing guidance on how best to evaluate moderate risk ED patients with acute chest pain. Without this guidance care patterns are likely to remain heterogeneous, inefficient, non- patient-centered, and unguided by the highest level of evidence. We hypothesize that data from this trial will support widespread implementation of a CARE strategy, which could improve the quality and value of care for millions of patients in the U.S. and beyond.

PROJECT NARRATIVE Each year 7 million patients seek care in U.S. Emergency Departments for chest pain. Most moderate-risk patients undergo hospitalization for expensive testing aimed at identifying a heart attack, which costs the healthcare system more than $3 billion annually without a clear improvement in patient outcomes. Our study will compare rapid outpatient vs hospitalization management to determine the best strategy (based on patient- centered measures and safe, equitable, and efficient resource use) for evaluating these patients.