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Direct Oral Anticoa...
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Carnicelli, Anthony P.Duke Univ, Div Cardiol, Durham, NC USA.;Duke Univ, Duke Clin Res Inst, Durham, NC USA.
(author)
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
- Article/chapterEnglish2022
Publisher, publication year, extent ...
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Ovid Technologies (Wolters Kluwer Health),2022
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Numbers
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LIBRIS-ID:oai:DiVA.org:uu-481436
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-481436URI
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https://doi.org/10.1161/CIRCULATIONAHA.121.056355DOI
Supplementary language notes
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Language:English
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Summary in:English
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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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.
Subject headings and genre
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Hong, HwanheeDuke Univ, Duke Clin Res Inst, Durham, NC USA.;Duke Univ, Dept Biostat & Bioinformat, Durham, NC USA.
(author)
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Connolly, Stuart J.McMaster Univ, Dept Med, Hamilton, ON, Canada.;Populat Hlth Res Inst, Hamilton, ON, Canada.
(author)
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Eikelboom, JohnMcMaster Univ, Dept Med, Hamilton, ON, Canada.;Populat Hlth Res Inst, Hamilton, ON, Canada.
(author)
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Giugliano, Robert P.Harvard Med Sch, Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA.;Thrombolysis Myocardial Infarct Study Grp, Boston, MA USA.
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Morrow, David A.Harvard Med Sch, Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA.;Thrombolysis Myocardial Infarct Study Grp, Boston, MA USA.
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Patel, Manesh R.Duke Univ, Div Cardiol, Durham, NC USA.;Duke Univ, Duke Clin Res Inst, Durham, NC USA.
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Wallentin, Lars,1943-Uppsala universitet,Kardiologi,Uppsala kliniska forskningscentrum (UCR)(Swepub:uu)larswall
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Alexander, John H.Duke Univ, Div Cardiol, Durham, NC USA.;Duke Univ, Duke Clin Res Inst, Durham, NC USA.
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Cecilia Bahit, M.INECO Neurociencias Orono, Dept Cardiol, Santa Fe, Argentina.
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Benz, Alexander P.Populat Hlth Res Inst, Hamilton, ON, Canada.
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Bohula, Erin A.Harvard Med Sch, Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA.;Thrombolysis Myocardial Infarct Study Grp, Boston, MA USA.
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Chao, Tze-FanTaipei Vet Gen Hosp, Div Cardiol, Taipei, Taiwan.
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Dyal, LeannePopulat Hlth Res Inst, Hamilton, ON, Canada.
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Ezekowitz, MichaelLankenau Inst Med Res, Wynnewood, PA USA.
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A.a. Fox, KeithUniv Edinburgh, Ctr Cardiovasc Sci, Edinburgh, Midlothian, Scotland.
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Gencer, BarisGeneva Univ Hosp, Div Cardiol, Geneva, Switzerland.;Univ Bern, Inst Primary Hlth Care BIHAM, Bern, Switzerland.
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Halperin, Jonathan L.Mt Sinai Med Ctr, Cardiovasc Inst, New York, NY 10029 USA.
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Hijazi, ZiadUppsala universitet,Uppsala kliniska forskningscentrum (UCR),Kardiologi(Swepub:uu)ziahi940
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Hohnloser, Stefan H.Goethe Univ Frankfurt, Dept Cardiol, Frankfurt, Germany.
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Hua, KaiyuanDuke Univ, Duke Clin Res Inst, Durham, NC USA.;Duke Univ, Dept Biostat & Bioinformat, Durham, NC USA.
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Hylek, ElaineBoston Univ, Dept Med, Sch Med, Boston, MA 02215 USA.
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Toda Kato, EriKyoto Univ, Dept Cardiol, Kyoto, Japan.
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Kuder, JuliaHarvard Med Sch, Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA.
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Lopes, Renato D.Duke Univ, Div Cardiol, Durham, NC USA.;Duke Univ, Duke Clin Res Inst, Durham, NC USA.
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Mahaffey, Kenneth W.Stanford Univ, Sch Med, Dept Med, Stanford Ctr Clin Res, Stanford, CA 94305 USA.
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Oldgren, Jonas,1964-Uppsala universitet,Kardiologi,Uppsala kliniska forskningscentrum (UCR)(Swepub:uu)jonaoldg
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Piccini, Jonathan P.Duke Univ, Duke Clin Res Inst, Durham, NC USA.
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Ruff, Christian T.Harvard Med Sch, Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA.;Thrombolysis Myocardial Infarct Study Grp, Boston, MA USA.
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Steffel, JanUniv Zurich, Dept Cardiol, Zurich, Switzerland.
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Wojdyla, DanielDuke Univ, Duke Clin Res Inst, Durham, NC USA.
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Granger, Christopher B.Duke Univ, Div Cardiol, Durham, NC USA.;Duke Univ, Duke Clin Res Inst, Durham, NC USA.
(author)
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Duke Univ, Div Cardiol, Durham, NC USA.;Duke Univ, Duke Clin Res Inst, Durham, NC USA.Duke Univ, Duke Clin Res Inst, Durham, NC USA.;Duke Univ, Dept Biostat & Bioinformat, Durham, NC USA.
(creator_code:org_t)
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In:Circulation: Ovid Technologies (Wolters Kluwer Health)145:4, s. 242-2550009-73221524-4539
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Carnicelli, Anth ...
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Hong, Hwanhee
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Connolly, Stuart ...
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Eikelboom, John
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Giugliano, Rober ...
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Morrow, David A.
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Patel, Manesh R.
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Wallentin, Lars, ...
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Alexander, John ...
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Cecilia Bahit, M ...
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Benz, Alexander ...
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Bohula, Erin A.
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Chao, Tze-Fan
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Dyal, Leanne
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Ezekowitz, Micha ...
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A.a. Fox, Keith
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Gencer, Baris
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Halperin, Jonath ...
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Hijazi, Ziad
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Hohnloser, Stefa ...
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Hua, Kaiyuan
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Hylek, Elaine
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Toda Kato, Eri
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Kuder, Julia
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Lopes, Renato D.
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Mahaffey, Kennet ...
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Oldgren, Jonas, ...
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Piccini, Jonatha ...
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Ruff, Christian ...
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Steffel, Jan
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Wojdyla, Daniel
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Granger, Christo ...
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