{"id":"838d5faab644","type":"article","url":"https://hartvaat.nl/2022/01/25/doac-s-versus-warfarine-bij-af-patient-niveau-netwerkmeta-analyse-van-gerandomis/","title":"DOAC's versus warfarine bij AF: patiënt-niveau netwerkmeta-analyse van gerandomiseerde trials","title_en":"Direct Oral Anticoagulants Versus Warfarin in Patients With Atrial Fibrillation: Patient-Level Network Meta-Analyses of Randomized Clinical Trials With Interaction Testing by Age and Sex.","category":"atriumfibrilleren","category_label":"Atriumfibrilleren","professions":["apotheker","cardioloog"],"tags":["anticoagulatie-kwetsbare-ouderen","doacs"],"journal":"Circulation","doi":"10.1161/CIRCULATIONAHA.121.056355","source_url":"https://doi.org/10.1161/CIRCULATIONAHA.121.056355","authors":["Anthony P Carnicelli","Hwanhee Hong","Stuart J Connolly","John Eikelboom","Robert P Giugliano","David A Morrow","Manesh R Patel","Lars Wallentin","John H Alexander","M Cecilia Bahit","Alexander P Benz","Erin A Bohula","Tze-Fan Chao","Leanne Dyal","Michael Ezekowitz","Keith A A Fox","Baris Gencer","Jonathan L Halperin","Ziad Hijazi","Stefan H Hohnloser","Kaiyuan Hua","Elaine Hylek","Eri Toda Kato","Julia Kuder","Renato D Lopes","Kenneth W Mahaffey","Jonas Oldgren","Jonathan P Piccini","Christian T Ruff","Jan Steffel","Daniel Wojdyla","Christopher B Granger"],"significance":9,"published":"2022-01-25","source_date":"2022-01-25","image":"","kennis":["https://hartvaat.nl/kennis/antistolling/doac-versus-vka-keuze/","https://hartvaat.nl/kennis/atriumfibrilleren/af-bij-ouderen/"],"congress":"","summary_en":"This patient-level network meta-analysis of all four DOACs versus warfarin in atrial fibrillation confirmed the class-wide superiority of DOACs for stroke prevention with less intracranial hemorrhage. The analysis also provided the first robust head-to-head indirect comparisons between individual DOACs.","created":"2026-07-03T10:29:36Z","updated":"2026-07-03T13:28:43Z","licence":"Citeer vrij, met bronvermelding en een link naar hartvaat.nl (de url van het record). Samenvattingen zijn redactioneel werk van HartVaat; de oorspronkelijke publicaties blijven van hun uitgevers (doi). Geen medisch advies.","body_markdown":"Patiënt-niveau netwerkmeta-analyse die alle vier DOAC's vergeleek met warfarine en onderling bij AF. Definitieve vergelijkende analyse.","abstract_original":"BACKGROUND: Direct oral anticoagulants (DOACs) are preferred over warfarin for stroke prevention in atrial fibrillation. Meta-analyses using individual patient data offer substantial advantages over study-level data. METHODS: We used individual patient data from the COMBINE AF (A Collaboration Between Multiple Institutions to Better Investigate Non-Vitamin K Antagonist Oral Anticoagulant Use in Atrial Fibrillation) database, which includes all patients randomized in the 4 pivotal trials of DOACs versus warfarin in atrial fibrillation (RE-LY [Randomized Evaluation of Long-Term Anticoagulation Therapy], ROCKET AF [Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation], ARISTOTLE [Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation], and ENGAGE AF-TIMI 48 [Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48]), to perform network meta-analyses using a stratified Cox model with random effects comparing standard-dose DOAC, lower-dose DOAC, and warfarin. Hazard ratios (HRs [95% CIs]) were calculated for efficacy and safety outcomes. Covariate-by-treatment interaction was estimated for categorical covariates and for age as a continuous covariate, stratified by sex. RESULTS: A total of 71 683 patients were included (29 362 on standard-dose DOAC, 13 049 on lower-dose DOAC, and 29 272 on warfarin). Compared with warfarin, standard-dose DOACs were associated with a significantly lower hazard of stroke or systemic embolism (883/29 312 [3.01%] versus 1080/29 229 [3.69%]; HR, 0.81 [95% CI, 0.74-0.89]), death (2276/29 312 [7.76%] versus 2460/29 229 [8.42%]; HR, 0.92 [95% CI, 0.87-0.97]), and intracranial bleeding (184/29 270 [0.63%] versus 409/29 187 [1.40%]; HR, 0.45 [95% CI, 0.37-0.56]), but no statistically different hazard of major bleeding (1479/29 270 [5.05%] versus 1733/29 187 [5.94%]; HR, 0.86 [95% CI, 0.74-1.01]), whereas lower-dose DOACs were associated with no statistically different hazard of stroke or systemic embolism (531/13 049 [3.96%] versus 1080/29 229 [3.69%]; HR, 1.06 [95% CI, 0.95-1.19]) but a lower hazard of intracranial bleeding (55/12 985 [0.42%] versus 409/29 187 [1.40%]; HR, 0.28 [95% CI, 0.21-0.37]), death (1082/13 049 [8.29%] versus 2460/29 229 [8.42%]; HR, 0.90 [95% CI, 0.83-0.97]), and major bleeding (564/12 985 [4.34%] versus 1733/29 187 [5.94%]; HR, 0.63 [95% CI, 0.45-0.88]). Treatment effects for standard- and lower-dose DOACs versus warfarin were consistent across age and sex for stroke or systemic embolism and death, whereas standard-dose DOACs were favored in patients with no history of vitamin K antagonist use (P=0.01) and lower creatinine clearance (P=0.09). For major bleeding, standard-dose DOACs were favored in patients with lower body weight (P=0.02). In the continuous covariate analysis, younger patients derived greater benefits from standard-dose (interaction P=0.02) and lower-dose DOACs (interaction P=0.01) versus warfarin. CONCLUSIONS: Compared with warfarin, DOACs have more favorable efficacy and safety profiles among patients with atrial fibrillation."}