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 registration https://www.

Clinicaltrials: gov . NCT01468701, NCT01671007.

Keywords: Anticoagulation; Atrial fibrillation; Dabigatran; Stroke prevention; Vitamin K antagonist.

Fig. 1

Design of GLORIA-AF. m, months; NOAC non-vitamin K antagonist oral anticoagulant; VKA vitamin K antagonist; y, years

Fig. 2

Patient flow. Data are from the patient set determined by the first of the 20 imputed datasets. ASA acetylsalicylic acid; OAC oral anticoagulant; PS propensity score; VKA vitamin K antagonist. ^aEligible patient set includes patients who were prescribed but did not take the antithrombotic therapies. This includes dabigatran (n = 32) and VKA (n = 52). These patients are excluded from the subsequent outcome analyses. ^bNs from individual treatment groups do not add up to the total treated N as we do not show all treatments and treatment combinations. ^cIn the dabigatran and VKA groups, patients with a PS less than the 1.5th percentile of the PS distribution for the dabigatran-exposed group and those with PS larger than the 98.5th percentile of the PS distribution for the VKA-exposed group were excluded. ^dLoss to follow-up is defined as not completed planned observation time and no information on vital status available

Fig. 3

Comparison of outcomes in patients treated with dabigatran or VKA at year 3: (a) in the PS-trimmed patient set (primary analysis); (b) in the PS-matched patient set with adjustment for unbalanced variables. CI confidence interval; CrCl creatinine clearance; HR hazard ratio; PS propensity score; VKA vitamin K antagonist. ^aAs the PS was calculated using baseline covariates with missing baseline covariates handled by multiple imputation, every patient had 20 estimated PSs, so there were 20 different PS-trimmed patient sets. Results presented are based on the average of the results from those sets. ^bCensoring patients after permanent discontinuation of initial treatment or study termination. ^cMultivariable Cox regression models were used to analyze comparative outcomes of dabigatran versus VKAs, along with a covariate selection procedure (see statistical methods section). ^dComposite outcome: stroke, systemic embolism, myocardial infarction, vascular death, and life-threatening bleeding, ^eTreatment, along with unbalanced parameters, are considered in the Cox regression model with a shared frailty factor. CrCl, previous oral anticoagulant use, and type of atrial fibrillation were adjusted in the model, as their standardized difference was > 10% in the matched datasets

Fig. 4

Kaplan–Meier plots of outcomes with dabigatran and VKAs in the PS-matched patient set. VKA vitamin K antagonist