Background Chronic kidney disease (CKD) is an independent risk factor for atrial fibrillation (AF), which is more prevalent among CKD patients than the general population. AF causes stroke or systemic embolism, leading to increased mortality. The conventional antithrombotic prophylaxis agent warfarin is often prescribed for the prevention of stroke, but risk of bleeding necessitates regular therapeutic monitoring. Recently developed direct oral anticoagulants (DOAC) are expected to be useful as alternatives to warfarin. Objectives To assess the efficacy and safety of DOAC including apixaban, dabigatran, edoxaban, and rivaroxaban versus warfarin among AF patients with CKD. Search methods We searched the Cochrane Kidney and Transplant Specialised Register (up to 1 August 2017) through contact with the Information Specialist using search terms relevant to this review. Studies in the Specialised Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal, and ClinicalTrials.gov. Selection criteria We included all randomised controlled trials (RCTs) which directly compared the efficacy and safety of direct oral anticoagulants (direct thrombin inhibitors or factor Xa inhibitors) with dose-adjusted warfarin for preventing stroke and systemic embolic events in non-valvular AF patients with CKD, defined as creatinine clearance (CrCl) or eGFR between 15 and 60 mL/min (CKD stage G3 and G4). Data collection and analysis Two review authors independently selected studies, assessed quality, and extracted data. We calculated the risk ratio (RR) and 95% confidence intervals (95% CI) for the association between anticoagulant therapy and all strokes and systemic embolic events as the primary efficacy outcome and major bleeding events as the primary safety outcome. Confidence in the evidence was assessing using GRADE. Main results Our review included 12,545 AF participants with CKD from five studies. All participants were randomised to either DOAC (apixaban, dabigatran, edoxaban, and rivaroxaban) or dose-adjusted warfarin. Four studies used a central, interactive, automated response system for allocation concealment while the other did not specify concealment methods. Four studies were blinded while the other was partially open-label. However, given that all studies involved blinded evaluation of outcome events, we considered the risk of bias to be low. We were unable to create funnel plots due to the small number of studies, thwarting assessment of publication bias. Study duration ranged from 1.8 to 2.8 years. The large majority of participants included in this study were CKD stage G3 (12,155), and a small number were stage G4 (390). Of 12,545 participants from five studies, a total of 321 cases (2.56%) of the primary efficacy outcome occurred per year. Further, of 12,521 participants from five studies, a total of 617 cases (4.93%) of the primary safety outcome occurred per year. DOAC appeared to probably reduce the incidence of stroke and systemic embolism events (5 studies, 12,545 participants: RR 0.81, 95% CI 0.65 to 1.00; moderate certainty evidence) and to slightly reduce the incidence of major bleeding events (5 studies, 12,521 participants: RR 0.79, 95% CI 0.59 to 1.04; low certainty evidence) in comparison with warfarin. Authors' conclusions Our findings indicate that DOAC are as likely as warfarin to prevent all strokes and systemic embolic events without increasing risk of major bleeding events among AF patients with kidney impairment. These findings should encourage physicians to prescribe DOAC in AF patients with CKD without fear of bleeding. The major limitation is that the results of this study chiefly reflect CKD stage G3. Application of the results to CKD stage G4 patients requires additional investigation. Furthermore, we could not assess CKD stage G5 patients. Future reviews should assess participants at more advanced CKD stages. Additionally, we could not conduct detailed analyses of subgroups and sensitivity analyses due to lack of data.

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Direct oral anticoagulants versus warfarin for preventing stroke and systemic embolic events among atrial fibrillation patients with chronic kidney disease

Long term prognosis of atrial fibrillation in ST-elevation myocardial infarction patients undergoing percutaneous coronary intervention

Disclosure: Prof Gregory Lip has acted as a consultant for Bayer, Astellas, Merck, Sanofi, BMS/Pfizer, Biotronik, Medtronic, Portola, Boehringer Ingelheim, Microlife Medtronic, and Daiichi Sankyo. He has also been on the speakers’ bureau for Bayer, BMS/Pfizer, Medtronic, Boehringer Ingelheim, Microlife, and Daiichi Sankyo. Prof Raffaele De Caterina has received fees, honoraria, and research funding from Sanofi-Aventis, Boehringer Ingelheim, Bayer, BMS/Pfizer, Daiichi Sankyo, and Novartis. Prof Robert Giugliano has received research grant support from Daiichi Sankyo and Merck, and honoraria for lectures/consulting from Daiichi Sankyo, Merck, Janssen, Pfizer, and Sanofi. Acknowledgements: Writing assistance provided by Dr Saroshi Amirthalingam, apothecom scopemedical Ltd. Support: The publication of this article was funded by Daiichi Sankyo Europe GmbH. The views and opinions expressed are those of the authors and not necessarily of Daiichi Sankyo. Citation: EMJ Cardiol. 2014;2:38-45.

Meeting the challenges in atrial fibrillation management: the role of new anticoagulants

Relationship between dose, anti-factor xa activity, and outcomes in patients randomized to edoxaban in the engage af-timi 48 trial

Cardiac structure and function and chads2 risk score in patients with atrial fibrillation: the effects anticoagulation with factor xa next generation in afthrombolysis in myocardial infarction 48 (engage af -timi 48) echocardiographic study

Indravadan Patel

Papers

Relationship between dose, anti-factor xa activity, and outcomes in patients randomized to edoxaban in the engage af-timi 48 trial

Cardiac structure and function and chads2 risk score in patients with atrial fibrillation: the effects anticoagulation with factor xa next generation in afthrombolysis in myocardial infarction 48 (engage af -timi 48) echocardiographic study