Registry-based endpoints without adjudication yielded comparable treatment effect estimates to adjudicated endpoints for beta-blocker therapy post-MI (HR 0.88 vs HR 0.85).
RCT (n=5,574)
randomised
Yes
Does registry-based endpoint assessment without adjudication provide comparable treatment effect estimates to adjudicated endpoints in patients with MI and LVEF ≥40%?
Registry-derived endpoints without adjudication provided comparable treatment effect estimates to adjudicated endpoints in a large cardiovascular trial, despite a higher incidence rate of unconfirmed events.
Hazard Ratio: 0.85 (95% CI 0.75–0.98)
Abstract Background Registry-based randomised clinical trials are increasingly dependent on registry-derived outcomes, providing advantages in feasibility and data capture. However, registry data may introduce bias through misclassification or incomplete information. In the BETAMI-DANBLOCK trial, we compared registry-based cardiovascular events with and without adjudication, using information from national registries, electronic health records, and patient reports. Purpose To investigate whether registry-based endpoints can substitute adjudicated endpoints without materially altering trial results. Methods BETAMI-DANBLOCK enrolled 5,574 patients with myocardial infarction (MI) and a left ventricular ejection fraction ≥40% from 2018 through 2024. Patients were randomised to beta-blocker therapy or no beta-blocker therapy. The primary endpoint events (death, MI, ischemic stroke, heart failure, unplanned coronary revascularisation, and ventricular arrhythmias) were identified from the Danish and Norwegian national patient registries, self-reported questionnaires, and medical records. All registry-identified events, except death, underwent blinded adjudication. We compared events with and without adjudication by calculating incidence rates and hazard ratios (HRs) for beta-blocker treatment versus controls. Results National registries had almost complete capture of events when compared to site-reporting. In total, 75% of the primary endpoint events identified through the registries were confirmed by adjudication. The confirmation rate was lower during the first six months and varied by event type (from 92% for ischemic stroke to 45% for unplanned coronary revascularisations). The incidence rate of the primary endpoint was 6.23 per 100 person-years using registry data without adjudication and 4.43 with adjudication. Estimated treatment effects were consistent for the primary endpoint (0.88, 95% confidence interval (CI): 0.78-0.98 without adjudication and 0.85, 95% CI: 0.75-0.98 with adjudication), with no apparent differences across event types. Conclusion Registry data provide treatment effect estimates comparable to those obtained from adjudicated data in BETAMI-DANBLOCK. However, adjudication substantially reduced the total number of endpoint events and event-specific misclassification was a limitation, particularly during the first months after the index event.Cumulative incidence of primary endpointFor image description, please refer to the figure legend and surrounding text. Forest plot of hazard ratiosFor image description, please refer to the figure legend and surrounding text.
Holmager et al. (Mon,) conducted a rct in Myocardial infarction with LVEF ≥40% (n=5,574). Beta-blocker therapy vs. No beta-blocker therapy was evaluated on Death, MI, ischemic stroke, heart failure, unplanned coronary revascularisation, and ventricular arrhythmias (HR 0.85, 95% CI 0.75-0.98). Registry-based endpoints without adjudication yielded comparable treatment effect estimates to adjudicated endpoints for beta-blocker therapy post-MI (HR 0.88 vs HR 0.85).