Bleeding outcomes associated with rivaroxaban and dabigatran in patients treated for atrial fibrillation: a systematic review and meta-analysis

Abstract

BackgroundWarfarin is commonly used as a secondary prevention of stroke in patients with atrial fibrillation (AF). However, limitations have been observed even with the use of this medication. Recently, several newer direct oral anticoagulants (DOACs) have been approved for use by the food and drug administrations. Unfortunately, these newer drugs have seldom been compared directly with each other. Therefore, this study aimed to compare the bleeding events associated with rivaroxaban and dabigatran in patients treated for non-valvular AF.MethodsEMBASE, Medline (National Library of Medicine) and the Cochrane Central Registry of Controlled Trials were searched for studies comparing rivaroxaban with dabigatran using the terms ‘rivaroxaban, dabigatran and atrial fibrillation’. Primary endpoints were: any bleeding outcomes, intracranial bleeding and gastro-intestinal (GI) bleeding. Secondary outcomes included stroke/systemic embolism (SE)/transient ischemic attack (TIA), venous thromboembolism and mortality. Odds ratios (OR) with 95% confidence intervals (CIs) were calculated. The pooled analyses were carried out with RevMan 5.3 software. All the authors had full access to the data and approved the manuscript as written.ResultsA total number of 4895 patients were included. This analysis showed that rivaroxaban was not associated with a significantly higher bleeding event when compared to dabigatran (OR: 1.28, 95% CI: 0.95–1.72; P = 0.11). GI bleeding was similarly manifested between these two DOACs (OR: 0.98, 95% CI: 0.43–2.25; P = 0.97). Even if intracranial bleeding was higher with the use of rivaroxaban, (OR: 2.18, 95% CI: 0.51–9.25; P = 0.29), the result was not statistically significant. Moreover, stroke/SE/TIA and venous thromboembolism were also not significantly different (OR: 0.81, 95% CI: 0.53–1.23; P = 0.32) and (OR: 2.06, 95% CI: 0.73–5.82; P = 0.17) respectively. However, even if mortality favored dabigatran (OR: 1.42, 95% CI: 0.99–2.06; P = 0.06), this result only approached statistical significance.ConclusionHead to head comparison showed that rivaroxaban was not associated with significantly higher bleeding events compared to dabigatran. Intracranial bleeding, GI bleeding, stroke/SE/TIA, venous thromboembolism and mortality were also not significantly different between these two DOACs. However, due to the limited number of patients analyzed, and which were mainly obtained from observational studies, this hypothesis might only be confirmed in future randomized trials. Furthermore, the CHADS2-VASC and HAS-BLED score which might play an important role in predicting bleeding risks should also not be ignored.

Comparative Effectiveness and Safety of Direct Oral Anticoagulants in Patients with Atrial Fibrillation: A Systematic Review and Meta-Analysis of Observational Studies

“…Moreover, there is a need to assess the comparative effectiveness and safety of DOACs in real-world settings. While four publications to date have systematically reviewed and metaanalyzed available real-world data, [7][8][9][10] one used outdated tools for the assessment of the risk of bias, [7] while others omitted bias assessment altogether. [8,9] Moreover, numerous studies reporting head-to-head comparisons among DOACs that were recently published were not included in these earlier works.…”

“…While four publications to date have systematically reviewed and metaanalyzed available real-world data, [7][8][9][10] one used outdated tools for the assessment of the risk of bias, [7] while others omitted bias assessment altogether. [8,9] Moreover, numerous studies reporting head-to-head comparisons among DOACs that were recently published were not included in these earlier works. [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27] Thus, the objective of this systematic review and meta-analysis of observational studies was to provide an up-to-date synthesis of the available real-world evidence on DOAC comparative effectiveness and safety in patients with AF, while thoroughly assessing the risk of bias of the included studies.…”

Normas de orientação clínica dos pacientes hipocoagulados em medicina dentária

“…2,3,18,32,33 Quando se considera esta opção, interrompe-se a TAC com VKAs 4-6 dias antes, com substituição por heparina, e retoma-se a TAC habitual 48-72h após a intervenção (Nível Ib, Classe IIb). 21 2.3) Regime Terapêutico com DOACs: A TAC com DOACs 7 deve ser mantida durante procedimentos cirúrgicos, 2,8,23,32,[34][35][36][37][38][39][40][41] todavia o risco de hemorragia inerente à intervenção deve ser considerado. Isto é, deve aceder-se à função renal do doente para perceber a que nível a suspensão temporária da terapia pode ser considerada (Tabela 2).…”

Antithrombotic therapy in coronary artery disease patients with atrial fibrillation

“…Fourth, there are insufficient data about the exact dose of antiplatelet and anticoagulant drugs, which may affect the analysis of adverse outcomes [34]. In addition, we did not compare the effects of the same type of antithrombotic drugs on patients [16,35]. Finally, NOAC did not enter the market until 2013 in China, and these drugs cannot be…”