Efficacy and safety of dabigatran versus warfarin from the RE-LY trial

Abstract

BackgroundCurrent data for atrial fibrillation (AF) and stroke are predominantly derived from North American and European patients. Although the burden of AF is high in Latin America (LA), little is known about current management of AF in the region.MethodsWe aimed to assess the consistency of efficacy and safety outcomes associated with dabigatran etexilate (DE) versus warfarin in patients with AF in LA from the RE-LY (Randomised Evaluation of Long-Term Anticoagulant Therapy) trial. Data from 956 LA patients and 17 157 non-LA patients were included in this analysis. χ2 test and Cox proportional regression analysis were performed. The primary efficacy outcome included all strokes or systemic embolism (SE). Main safety outcome was major bleeding.ResultsLA patients were more often female, had higher proportion of permanent AF and lower creatinine clearance, among other characteristics. Vitamin K antagonist use at randomisation and time in therapeutic range were lower in LA than in non-LA patients (44% vs 63%, p<0.001; and 61.3±22.6% vs 64.6±19.6%, p=0.015, respectively). Efficacy endpoints were 0.91% versus 1.68% for DE 150 mg twice daily versus warfarin, respectively. Stroke/SE risk was lower in LA patients treated with DE 150 mg twice daily compared with warfarin, although not significant (HR 0.54; 95% CI 0.18 to 1.62). The annual stroke/SE rates for DE 110 mg twice daily versus warfarin were 1.82 versus 1.68, also not significantly different (HR 1.09; CI 0.44 to 2.67). There were no treatment-by-region interactions for either dose of DE on efficacy and safety outcomes.ConclusionDespite differences in the clinical profile and AF management, the efficacy and safety benefits of dabigatran over warfarin in LA patients relative to non-LA patients are consistent with those observed in the main RE-LY trial.

Meta-analysis of the efficacy and safety of non-vitamin K antagonist oral anticoagulants with warfarin in Latin American patients with atrial fibrillation

“…[ 32 ] Our meta-analysis could add contemporary data on clinical characteristics, management and outcomes of LatAm patients, suggesting the consistency of effects regardless of geographical regions, and more favorable efficacy and safety profiles in patients treated with NOACs. Consistent with the previous data, [ 4 , 5 , 18 , 19 ] we indicated that the use of NOACs were at least non-inferior to warfarin for stroke prevention in LatAm patients with AF. Our current meta-analysis provided an important contemporary picture of the response to anticoagulation therapy for LatAm patients; and might provide encouragement to select the use of NOACs for reducing AF-related stroke and death in LatAm patients.…”

“…Based on the title-/abstract- screenings, 10 studies were excluded because they were review articles or observational studies. And subsequently, 6 full-text studies [ 3 – 6 , 18 , 19 ] were reviewed in more detail, 2 of which were excluded because participants had a substantial overlap. [ 3 , 6 ] Finally, a total of 4 trials (2 phase III RCTs including ROCKET AF [rivaroxaban] and apixaban for reduction in stroke and other thromboembolic events in atrial fibrillation [ARISTOTLE] [apixaban], 2 sub-analyses of RCTs including randomized evaluation of long-term anticoagulation therapy [RE-LY] [dabigatran], and effective anticoagulation with factor Xa next generation in atrial fibrillation-thrombolysis in myocardial infarction 48 [ENGAGE AF-TIMI 48] [edoxaban]) [ 4 , 5 , 18 , 19 ] were included in this meta-analysis.…”

Evaluation of the anticoagulant effect of vitamin K antagonists in patients with non-valvular atrial fibrilation

“…In ROCKET-AF study the mean TTR was 55.2%, but the values in Western Europe and North America were significantly higher, 63% and 64%, respectively 20 . In ARISTOTLE study the mean TTR was 66% 21 , in RE-LY study 67.2%, with the highest values of 77% in Sweden and 74% in Finland and Australia 10,11 . On the other hand, Gateman D et al calculated the mean TTR in St. Paul Family Health Network in Ontario of 58.05% 8 , while the mean TTR in the study of Ciurus T et al is 76% that is considered to represent excellent anticoagulation control 1 .…”

“…But although TTR is routinely assessed, there is no consensus on acceptable target for TTR in practice. Active-W study suggested a minimum TTR of 58% in order to show a benefit of oral anticoagulant therapy over antiplatelet therapy in terms of preventing vascular events 9 , RE-LY study on Portuguese patients showed mean TTR of 61% 10,11 , Thrombosis Canada states that good INR control is when TTR is more than 60% 12 , but there are studies that report elevated level of TTR on 74% as a measure of effective anticoagulation 8,13 . It is known that many factors correlate with TTR, and the most important are age, sex, smoking, concomitant drugs, alcohol, comorbid medical and psychiatric conditions 14 .…”

Atrial Fibrillation and Diabetes Mellitus: the Control of Thromboembolic Risk

“…Исторически первыми препаратами для профилактики инсульта при ФП являются антагонисты витамина К (варфарин). Мета-анализ исследований показал, ОБЗОРЫ § что применение препаратов этой группы у больных с ФП снижает риск развития инсультов по сравнению с отсутствием антикоагулянтной терапии [42].…”