Lead Investigator: Daniel Caldeira, University of Lisbon/CCUL
Title of Proposal Research: The clinical impact of dabigratran in patients with non-valvular atrial fibrillation who had a fall or head injury: a retrospective analysis of RE-LY
Vivli Data Request: 5294
Funding Source: None.
Potential Conflicts of Interest: Participated in educational meetings and/or attended a conferences or symposia (including travel, accommodation and/or hospitality) with Bristol-Myers Squibb, Bayer, Boehringer Ingelheim, Daiichi Sankyo, Merck Serono, Ferrer, Pfizer, Novartis and Roche.
Summary of the Proposed Research:
Atrial fibrillation is the most prevalent persistent arrhythmia and it is estimated that this condition is present in 33.5 million individuals worldwide. In this arrhythmia, some of heart chamber lose the contractility (atrial chambers) which leads to an increased risk of clot formation and migration to other places, such as the brain leading to stroke. Anticoagulants are essential to prevent clot formation and stroke in patients with atrial fibrillation. All these drugs increase the risk of bleeding and one of the barriers to prescribe these drugs was the risk of bleeding in the cranius. To overcome these hypothetical barriers, some studies claimed that it would be needed 295 falls to have 1 intracranial hemorrhage. Recently, novel anticoagulants showed to have a better safety profile than the older anticoagulants (warfarin) which includes a lower risk of intracranial hemorrhage. Dabigatran is one of these novel drugs but it is not known whether it improve In this study we aim to evaluate the outcomes of patients with atrial fibrillation (AF) that had a fall or head injury, assessing the data reported in the clinical trial RE-LY to evaluate whether dabigatran treatment leads to lower risk of complications in this setting. Briefly, we will explore the potential protective role of dabigatran in traumatic events.
Statistical Analysis Plan:
OBJECTIVES AND OUTCOMES
In this study we aimed to:
1. evaluate the frequency of falls and/or head injury in patients with atrial fibrillation treated with oral anticoagulants and characterize clinical characteristics and outcomes of these patients.
2. Evaluate the clinical impact of dabigatran vs. warfarin in patients that had a falls and/or head injury.
– Major bleeding
– Intracranial haemorrhage
– All bleeding events
– All cause mortality
Rationale for Study Selection and Selection of Populations/Participants
We intend to apply for data from phase III trial of dabigatran vs. warfarin.
Patients with atrial fibrillation with increased thromboembolic risk candidates for oral anticoagulation according to the inclusion criteria of the trials
Data regarding demographic (age, gender, weight, height, body-mass index) and clinical characteristics (previous history of hypertension, heart failure, New York Heart Association class, diabetes, stroke/TIA, coronary disease, myocardial infarction, peripheral artery disease, smoking, history of bleeding, haemoglobin, chronic kidney disease (eGFR<60 mL/min), prior medication, type of atrial fibrillation).
Frequency of falls and/or head injury as an adverse event (AE) and evaluate the risk any of the defined outcomes 30 days after the AE, and the risk of outcomes throughout the trial.
Compare the characteristics and outcomes of patients that had falls/head injury throughout the trials and compare with those without falls/head injury.
DAbigatran vs Warfarin in patients with falls/head injury
Statistical Analysis Plan
The sample will be characterized through proportions, means or medians with their variability measures (SD or IQR).
The number of events will be estimated using a percentage but also through the incidence using the metric persons-years.
Among patients with falls/head injury we intend to evaluate NOACs vs. Warfarin:
Outcomes 30 days after the event, namely: Major bleeding, Intracranial haemorrhage, All bleeding events, All-cause mortality.
The measure of effect will be the ratio of time to events among the different comparison, using the adjusted hazard ratios to express the estimate.
Kaplan-meyer curves and log-rank tests will be derived as well as survival curves and Cox-regression.
The Cox-regressions were applied in 2 phases: 1) univariable model regression to evaluate the unadjusted characteristics among the different groups and different outcomes separately. 2) a baseline-adjusted Cox model, including the adjustment to covariates found to be significantly different in the first phase and prespecified covariates deemed to be relevant for the different analyses.
If other datasets from Non-vitamin K antagonist oral anticoagulants (NOACs) trials are available we will perform an individual patient data meta-analysis to evaluate NOACs vs. VKA in patients with fall/head injury. This method would have more power to capture the possible risk reduction of intracranial hemorrhage in these patients, evaluating the same outcomes.
Randomized Evaluation of Long Term Anticoagulant Therapy (RE-LY) Comparing the Efficacy and Safety of Two Blinded Doses of Dabigatran Etexilate With Open Label Warfarin for the Prevention of Stroke and Systemic Embolism in Patients With Non-valvular Atrial Fibrillation: Prospective, Multi-centre, Parallel-group, Non-inferiority Trial (RE-LY Study)
Sponsor: Boehringer Ingelheim
Study ID: NCT00262600
Sponsor ID: 1160.26
Caldeira, D., Alves da Silva, P. and Pinto, F.J., 2023. Clinical outcomes of anticoagulated patients with atrial fibrillation after falls or head injury: insights from RE-LY. Stroke. 2023;54:1656–1659. doi: 10.1161/STROKEAHA.122.041628