Effectiveness and safety of dabigatran therapy in daily-care patients with atrial fibrillation

Abstract

The effectiveness and safety of dabigatran for stroke prevention in atrial fibrillation (SPAF) demonstrated in RE-LY needs to be confirmed in daily care. To evaluate treatment persistence, effectiveness and safety of dabigatran therapy in SPAF patients in daily care, we used data from an ongoing, prospective, non-interventional registry of more than 2,500 patients on novel oral anticoagulants in daily care. Between October 1, 2011 and February 28, 2013, a total of 341 SPAF patients receiving dabigatran were enrolled. The combined endpoint of stroke/transient ischaemic attack/systemic embolism occurred at a rate of 2.93/100 patient-years in the intention-to-treat analysis (95%-CI 1.6-4.9) and at 1.9/100 patient-years in the on treatment analysis (events within three days after last intake). On-treatment rates were higher in patients selected for 110 mg dabigatran (n=183) BID compared to the 158 patients selected for 150 mg BID (2.88 [95% CI 1.16- 5.93] vs 0.86/100 patient-years [95% CI 0.10, 3.12]). On treatment, major bleeding occurred at a rate of 2.3/100 patient-years and numerically more often in patients receiving the 110 mg BID dose compared to the 150 mg BID dose (2.9 vs 1.7/100 patient-years). Dabigatran treatment discontinuation occurred in a total of 124 patients during follow-up (25.8 per 100 patient-years in Kaplan Meier analysis). Main reasons for treatment discontinuation were non-bleeding side effects. Our data contribute to the confirmation of effectiveness and relative safety of dabigatran in unselected patients in daily care. However, discontinuation rates are not lower than those reported for patients treated with vitamin K antagonists.

Vitamin K antagonists: relative strengths and weaknesses vs. direct oral anticoagulants for stroke prevention in patients with atrial fibrillation

“…Data from the Dresden NOAC Registry suggest that rates of major bleeding may be lower with rivaroxaban, apixaban and dabigatran therapy compared with VKA therapy [13, 16, 18, 90]. Moreover, these data show that real-life rates of major bleeding with rivaroxaban were similar (Dresden NOAC Registry [16, 102]) or lower (XANTUS [26]) compared with findings from ROCKET AF [16, 102].…”

“…DOACs were at least as good as, if not superior to, warfarin in terms of efficacy for the prevention of stroke in patients with non-valvular AF and also offered a better safety profile (all four major trials consistently indicated reduced rates of intracranial and fatal or life-threatening bleeding compared with the respective warfarin arm) [32, 52, 58, 102, 109]. Real-world evidence of DOACs is accumulating, and available data support the findings of the phase III clinical studies (for example [13, 15, 16, 18, 26, 117, 121]). In general, current guidelines recommend DOACs in preference to VKAs [27, 114] or as an alternative to VKAs [74, 94] for prevention of stroke or systemic embolism in patients with non-valvular AF.…”

Thromboembolic events, bleeding, and drug discontinuation in patients with atrial fibrillation on anticoagulation: a prospective hospital-based registry

“…We also observed a rate of myocardial infarction of 0.5 per 100 patients-years and a rate of VTE of 2.8 per 100 patient-years. Firstly, it is interesting that a cohort reported by Beyer-Westendorf et al from a population of primary-care AF patients with similar baseline stroke risk factors and similar stroke rate had no VTE events at all [2]. Thus, the risk of VTE in AF patients, especially when medically ill or frail, should not be neglected.…”

“…Direct oral anticoagulants (DOACs), including the direct thrombin inhibitor dabigatran and the direct factor Xa inhibitors rivaroxaban, apixaban, and edoxaban, have shifted the paradigm of anticoagulation treatment from routine drug monitoring and dose adjustment to a one-size-fits-all strategy, and changed clinical practice of oral anticoagulation. Real-world data have confirmed the efficacy and safety of DOACs for stroke prevention [2, 3]. However, in a hospital-based patient population with AF, comorbid conditions, comedications and surgical interventions may complicate treatment with anticoagulant drugs, which has not been specifically addressed in previous real-world investigation.…”

How to REVISIT the increasing “real world” evidence for stroke prevention in non-valvular atrial fibrillation?

“…The paper by Coleman et al 3 is one of a deluge of papers on real world observational data on the comparative effectiveness of the various non-Vitamin K antagonist oral anticoagulants (NOACs) against warfarin [8][9][10][11] , or against each other [12][13][14] . Many cohorts have had substantially larger sample sizes and, importantly, the present analysis provides no data on dabigatran despite the extensive real world data published for this drug 15 .…”