Registry-based randomised clinical trial: efficient evaluation of generic pharmacotherapies in the contemporary era

Randomised clinical trials are the gold standard for testing the effectiveness of clinical interventions. However, increasing complexity and associated costs may limit their application in the investigation of key cardiovascular knowledge gaps such as the re-evaluation of generic pharmacotherapies. The registry-based randomised clinical trial (RRCT) leverages data sampling from nationwide quality registries to facilitate high participant inclusion rates at comparably low costs and, therefore, may offer a mechanism by which such clinical questions may be answered. To date, a number of studies have been conducted using such trial designs, but uncritical use of the RRCT design may lead to erroneous conclusions. The current review provides insights into the strengths and weaknesses of the RRCT, as well as provides an exploratory example of how a trial may be designed to test the long-term effectiveness of beta blockers in patients with myocardial infarction who have preserved left ventricular systolic function

Galectin 3 is a powerful risk predictor for recurrent coronary events in acute coronary syndrome patients

Background: Galectin 3 and ST2 are mediators and biomarkers of myocardial fibrosis and remodeling that have recently entered the clinical practice guidelines as prognostic factors in heart failure patients. Elevated galectin 3 and ST2 levels in acute myocardial infarction patients have also been associated with increased incidence of adverse events during follow-up. Purpose: We aimed to assess the comparative ability of Galectin 3 and ST2 to offer additional prognostic information for risk stratification in acute coronary syndrome (ACS) patients, on top of traditional cardiovascular risk factors and other established prognostic biomarkers. Methods: We measured the levels of galectin 3, ST2, N-terminal pro-B type natriuretic peptide (NTproBNP), high-sensitivity C-reactive protein (hsCRP), highsensitivity troponin T (TnT), cystatin C, and lipids in plasma collected from 524 ACS patients (STEMI, non-STEMI and unstable angina) on day 1 following the acute event. Biomarker levels were correlated with the risk to develop recurrent coronary events, in linear regression models adjusted for age, sex and traditional risk factors (smoking, diabetes mellitus, hypertension, LDL, HDL and triglycerides). Results: During a mean follow-up period of 2.13 years, 63 (12%) of the patients suffered a new coronary event. Baseline galectin 3, ST2, hsCRP, NTproBNP and cystatin C were significantly higher in these patients compared to the event-free controls. In a Cox proportional hazards model with forward step selection that included all biomarkers alongside traditional risk factors, age (HR per year of age 1.06, 95% CI 1.03-1.09), galectin 3 (HR per SD log increase 1.88, 95% CI 1.41- 2.51) and cystatin C (HR per SD log increase 1.39, 95% CI 1.12-1.74) were selected as the only independent predictors of recurrent events in the population. In receiver operating curve (ROC) analyses, addition of galectin 3 significantly improved the c-statistic of the model based on traditional risk factors alone (0.81 vs. 0.76,

Routine Oxygen Therapy Does Not Improve Health-Related Quality of Life in Patients With Acute Myocardial Infarction—Insights From the Randomized DETO2X-AMI Trial

Background: After decades of ubiquitous oxygen therapy in all patients with acute myocardial infarction (MI), recent guidelines are more restrictive based on lack of efficacy in contemporary trials evaluating hard clinical outcomes in patients without hypoxemia at baseline. However, no evidence regarding treatment effects on health-related quality of life (HRQoL) exists. In this study, we investigated the impact of routine oxygen supplementation on HRQoL 6–8 weeks after hospitalization with acute MI. Secondary objectives included analyses of MI subtypes, further adjustment for infarct size, and oxygen saturation at baseline and 1-year follow-up. Methods: In the DETermination of the role of Oxygen in suspected Acute Myocardial Infarction (DETO2X-AMI) trial, 6,629 normoxemic patients with suspected MI were randomized to oxygen at 6 L/min for 6–12 h or ambient air. In this prespecified analysis, patients younger than 75 years of age with confirmed MI who had available HRQoL data by European Quality of Life Five Dimensions questionnaire (EQ-5D) in the national registry were included. Primary endpoint was the EQ-5D index assessed by multivariate linear regression at 6–10 weeks after MI occurrence. Results: A total of 3,086 patients (median age 64, 22% female) were eligible, 1,518 allocated to oxygen and 1,568 to ambient air. We found no statistically significant effect of oxygen therapy on EQ-5D index (−0.01; 95% CI: −0.03–0.01; p = 0.23) or EQ-VAS score (−0.57; 95% CI: −1.88–0.75; p = 0.40) compared to ambient air after 6–10 weeks. Furthermore, no significant difference was observed between the treatment groups in EQ-5D dimensions. Results remained consistent across MI subtypes and at 1-year follow-up, including further adjustment for infarct size or oxygen saturation at baseline. Conclusions: Routine oxygen therapy provided to normoxemic patients with acute MI did not improve HRQoL up to 1 year after MI occurrence. Clinical Trial Registration: ClinicalTrials.gov number, NCT01787110.

Poor long-term prognosis in patients admitted with strong suspicion of acute myocardial infarction but discharged with another diagnosis

Background: Characteristics and prognosis of patients admitted with strong suspicion of myocardial infarction (MI) but discharged without an MI diagnosis are not well-described. Objectives: To compare background characteristics and cardiovascular outcomes in patients discharged with or without MI diagnosis. Methods: The DETermination of the role of Oxygen in suspected Acute Myocardial Infarction (DETO2X-AMI) trial compared 6629 patients with strong suspicion of MI randomized to oxygen or ambient air. The main composite end-point of this subgroup analysis was the incidence of all-cause death, rehospitalization with MI, heart failure (HF) or stroke during a follow-up of 2.1 years (median; range: 1–3.7 years) irrespective of randomized treatment. Results: 1619 (24%) received a non-MI discharge diagnosis, and 5010 patients (76%) were diagnosed with MI. Groups were similar in age, but non-MI patients were more commonly female and had more comorbidities. At thirty days, the incidence of the composite end-point was 2.8% (45 of 1619) in non-MI patients, compared to 5.0% (250 of 5010) in MI patients with lower incidences in all individual end-points. However, for the long-term follow-up, the incidence of the composite end-point increased in the non-MI patients to 17.7% (286 of 1619) as compared to 16.0% (804 of 5010) in MI patients, mainly driven by a higher incidence of all-cause death, stroke and HF. Conclusions: Patients admitted with a strong suspicion of MI but discharged with another diagnosis had more favourable outcomes in the short-term perspective, but from one year onwards, cardiovascular outcomes and death deteriorated to a worse long-term prognosis. © 2021 The Authors. Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicin