Providing Rapid Out of Hospital Acute Cardiovascular Treatment 4 (PROACT-4).

BACKGROUND: Whether prehospital point-of-care (POC) troponin further accelerates the time to diagnosis in patients with chest pain (CP) is unknown. We conducted a randomized trial of POC-Troponin testing in the ambulance. METHODS AND RESULTS: Patients with chest pain presenting by ambulance were randomized to usual care (UC) or POC-Troponin; ST-elevation myocardial infarction patients or those with noncardiovascular symptoms were excluded. Pre-hospital high-sensitivity troponin was analyzed on a POC device and available to the paramedic and emergency department (ED) staff. The final diagnosis was centrally adjudicated. The primary endpoint was time from first medical contact to discharge from ED or admission to hospital. We randomized 601 patients in 19 months; 296 to UC and 305 to POC-Troponin. After ambulance arrival, the first troponin was available in 38 minutes in POC-Troponin and 139 minutes in UC. In POC-Troponin, the troponin was >0.01 ng/mL in 17.4% and >0.03 ng/mL in 9.8%. Patients spent a median of 9.0 hours from first medical contact to final disposition, and 165 (27.4%) were admitted to the hospital. The primary endpoint was shorter in patients randomized to POC-Troponin (median 8.8 hours [6.2-10.8] compared to UC (median 9.1 hours [6.7-11.2]; P=0.05). There was no difference in the secondary endpoint of repeat ED visits, hospitalizations, or death in the next 30 days. CONCLUSIONS: In this broad population of patients with CP, ambulance POC-Troponin accelerated the time to final disposition. Enhanced and more cost-effective early ED discharge of the majority of patients with CP calling 911 is an unrealized opportunity. CLINICAL TRIAL REGISTRATION: URL: https://www.ClinicalTrials.gov/. Unique identifier: NCT01634425.

Providing Rapid Out of Hospital Acute Cardiovascular Treatment 3 (PROACT-3).

BACKGROUND: The outcomes of acute cardiovascular symptom presentations are potentially modifiable with the use of biomarkers to accelerate accurate diagnosis. This randomized trial tested troponin and B-type natriuretic peptide before hospital guidance in patients with acute cardiovascular symptoms. METHODS: Patients with either chest pain or shortness of breath were randomized to usual care or biomarkers analyzed using a point-of-care device in the ambulance. The primary end point was time to final disposition (discharge from the emergency department or admission to hospital). The trial was stopped prematurely because of less than expected enrollment of patients of interest and no difference in the primary end point. RESULTS: We randomized 491 patients; 480 formed the final cohort. Patients were 49% male; median age 70 years; 42% had previous acute coronary syndrome; and 28% diabetes. The B-type natriuretic peptide level before hospital arrival was ≥ 100 pg/mL in 36.4%. Troponin was > 0.03 ng/mL in 13.4%; 3.6% had troponin > 0.1 ng/mL. After adjudication, 16% had acute coronary syndrome, 6.5% acute heart failure, 3.3% angina, and 74.2% another diagnosis. The primary end point was 9.2 (interquartile range, 7.3-11.1) hours in the biomarker group and 8.8 (interquartile range, 6.3-12.1) hours in the usual care group (P = 0.6). None died in the ambulance or in the emergency department: all-cause 30-day mortality was 2.1% (usual care) and 1.7% (biomarker). CONCLUSIONS: To our knowledge, this is the first randomized trial of biomarkers before hospital arrival to guide emergency management of suspected acute cardiovascular disease which showed no benefit and was terminated early because of futility. The results have important implications for the use of biomarkers in emergency management of heart disease and for the design of future randomized trials on this important topic.