Dabigatran versus vitamin K antagonists for atrial fibrillation in clinical practice: final outcomes from Phase III of the GLORIA-AF registry

Abstract

Background Prospectively collected, routine clinical practice-based data on antithrombotic therapy in non-valvular atrial fibrillation (AF) patients are important for assessing real-world comparative outcomes. The objective was to compare the safety and effectiveness of dabigatran versus vitamin K antagonists (VKAs) in patients with newly diagnosed AF. Methods and results GLORIA-AF is a large, prospective, global registry program. Consecutive patients with newly diagnosed AF and CHA2DS2-VASc scores ≥ 1 were included and followed for 3 years. To control for differences in patient characteristics, the comparative analysis for dabigatran versus VKA was performed on a propensity score (PS)-matched patient set. Missing data were multiply imputed. Proportional-hazards regression was used to estimate hazard ratios (HRs) for outcomes of interest. Between 2014 and 2016, 21,300 eligible patients were included worldwide: 3839 patients were prescribed dabigatran and 4836 VKA with a median age of 71.0 and 72.0 years, respectively; > 85% in each group had a CHA2DS2-VASc-score ≥ 2. The PS-matched comparative analysis for dabigatran and VKA included on average 3326 pairs of matched initiators. For dabigatran versus VKAs, adjusted HRs (95% confidence intervals) were: stroke 0.89 (0.59–1.34), major bleeding 0.61 (0.42–0.88), all-cause death 0.78 (0.63–0.97), and myocardial infarction 0.89 (0.53–1.48). Further analyses stratified by PS and region provided similar results. Conclusions Dabigatran was associated with a 39% reduced risk of major bleeding and 22% reduced risk for all-cause death compared with VKA. Stroke and myocardial infarction risks were similar, confirming a more favorable benefit-risk profile for dabigatran compared with VKA in clinical practice. Clinical trial registrationhttps://www.clinicaltrials.gov. NCT01468701, NCT01671007. Graphical abstract

Adherence to the Atrial Fibrillation Better Care (ABC) pathway and the risk of major outcomes in patients with atrial fibrillation: a post-hoc analysis from the prospective GLORIA-AF Registry

“…The primary papers from GLORIA-AF Phase III registry comparing the different anticoagulation strategies have recently been published. 21 , 22 …”

Clinical Complexity Domains, Anticoagulation, and Outcomes in Patients with Atrial Fibrillation: A Report from the GLORIA-AF Registry Phase II and III

“…Complete details on the design of the GLORIA-AF study have been previously reported, 20,21 as well as the primary papers comparing dabigatran versus VKA and other NOACs. 22,23 Briefly, patients with new-onset nonvalvular AF and CHA 2 DS 2 -VASc score !1 were consecutively enrolled between 2011 and 2016 (2011-2014 for phase II, and 2014-2016 for phase III). Patients enrolled in phase II who initiated dabigatran were prospectively followed up for 2 years, while all patients enrolled in phase III (irrespective of the antithrombotic treatment) were followed up for 3 years.…”

“…Details on follow-up and outcomes for phase II and phase III were reported elsewhere. 23,25 During follow-up, data regarding treatment discontinuation and major adverse outcomes were collected, until study withdrawal, death, or end of study. Nonpersistence was defined as either discontinuation or study termination.…”

“…In the final model 3, the risk of OAC discontinuation was significantly higher in frail elderly patients (HR: 1.30, 95% CI: 1.00-1.69), those with CKD (HR: 1.10, 95% CI: 1.02-1.20), and in those with two or more complexity criteria (HR: 1.39, 95% CI: 1. 23…”

“…Full details on inclusion and exclusion criteria were described elsewhere. 23 Patients aged 18 years or older, with a recent diagnosis of AF (<3 months, except in Latin America where <4.5 months cut-off was used) and a CHA 2 DS 2 -VASc score !1, who provided written informed consent were considered eligible for inclusion. The protocol of the study was approved by the European Medicines Agency, and the study was conducted in accordance with the principles of Good Clinical Practice and the Declaration of Helsinki.…”