Apixaban for Patients With Atrial Fibrillation on Hemodialysis: A Multicenter Randomized Controlled Trial.

Autor: Pokorney SD; Duke Clinical Research Institute, Duke University Medical Center, Durham, NC (S.D.P., H.R.A.-K., D.G., P.D., R.D.L., J.P.M., J.A.R., K.L.T., J.B.W., C.B.G.)., Chertow GM; Stanford University, Palo Alto, CA (G.M.C., K.W.M., K.M.)., Al-Khalidi HR; Duke Clinical Research Institute, Duke University Medical Center, Durham, NC (S.D.P., H.R.A.-K., D.G., P.D., R.D.L., J.P.M., J.A.R., K.L.T., J.B.W., C.B.G.)., Gallup D; Duke Clinical Research Institute, Duke University Medical Center, Durham, NC (S.D.P., H.R.A.-K., D.G., P.D., R.D.L., J.P.M., J.A.R., K.L.T., J.B.W., C.B.G.)., Dignacco P; Duke Clinical Research Institute, Duke University Medical Center, Durham, NC (S.D.P., H.R.A.-K., D.G., P.D., R.D.L., J.P.M., J.A.R., K.L.T., J.B.W., C.B.G.)., Mussina K; Stanford University, Palo Alto, CA (G.M.C., K.W.M., K.M.)., Bansal N; University of Washington, Seattle (N.B., D.A.G.)., Gadegbeku CA; Temple University, Philadelphia, PA (C.A.G.)., Garcia DA; University of Washington, Seattle (N.B., D.A.G.)., Garonzik S; Bristol Myers-Squibb, Princeton, NJ (S.G.)., Lopes RD; Duke Clinical Research Institute, Duke University Medical Center, Durham, NC (S.D.P., H.R.A.-K., D.G., P.D., R.D.L., J.P.M., J.A.R., K.L.T., J.B.W., C.B.G.)., Mahaffey KW; Stanford University, Palo Alto, CA (G.M.C., K.W.M., K.M.)., Matsuda K; Stanford University, Palo Alto, CA (G.M.C., K.W.M., K.M.).; Frenova Renal Research, Waltham, MA (K.M.)., Middleton JP; Duke Clinical Research Institute, Duke University Medical Center, Durham, NC (S.D.P., H.R.A.-K., D.G., P.D., R.D.L., J.P.M., J.A.R., K.L.T., J.B.W., C.B.G.)., Rymer JA; Duke Clinical Research Institute, Duke University Medical Center, Durham, NC (S.D.P., H.R.A.-K., D.G., P.D., R.D.L., J.P.M., J.A.R., K.L.T., J.B.W., C.B.G.)., Sands GH; Pfizer, New York, NY (G.H.S.)., Thadhani R; Massachussetts General and Brigham and Women's Hospitals, Boston (R.T.)., Thomas KL; Duke Clinical Research Institute, Duke University Medical Center, Durham, NC (S.D.P., H.R.A.-K., D.G., P.D., R.D.L., J.P.M., J.A.R., K.L.T., J.B.W., C.B.G.)., Washam JB; Duke Clinical Research Institute, Duke University Medical Center, Durham, NC (S.D.P., H.R.A.-K., D.G., P.D., R.D.L., J.P.M., J.A.R., K.L.T., J.B.W., C.B.G.)., Winkelmayer WC; Baylor College of Medicine, Houston, TX (W.C.W.)., Granger CB; Duke Clinical Research Institute, Duke University Medical Center, Durham, NC (S.D.P., H.R.A.-K., D.G., P.D., R.D.L., J.P.M., J.A.R., K.L.T., J.B.W., C.B.G.).
Jazyk: angličtina
Zdroj: Circulation [Circulation] 2022 Dec 06; Vol. 146 (23), pp. 1735-1745. Date of Electronic Publication: 2022 Nov 06.
DOI: 10.1161/CIRCULATIONAHA.121.054990
Abstrakt: Background: There are no randomized data evaluating the safety or efficacy of apixaban for stroke prevention in patients with end-stage kidney disease on hemodialysis and with atrial fibrillation (AF).
Methods: The RENAL-AF trial (Renal Hemodialysis Patients Allocated Apixaban Versus Warfarin in Atrial Fibrillation) was a prospective, randomized, open-label, blinded-outcome evaluation (PROBE) of apixaban versus warfarin in patients receiving hemodialysis with AF and a CHA 2 DS 2 -VASc score ≥2. Patients were randomly assigned 1:1 to 5 mg of apixaban twice daily (2.5 mg twice daily for patients ≥80 years of age, weight ≤60 kg, or both) or dose-adjusted warfarin. The primary outcome was time to major or clinically relevant nonmajor bleeding. Secondary outcomes included stroke, mortality, and apixaban pharmacokinetics. Pharmacokinetic sampling was day 1, day 3, and month 1.
Results: From January 2017 through January 2019, 154 patients were randomly assigned to apixaban (n=82) or warfarin (n=72). The trial stopped prematurely because of enrollment challenges. Time in therapeutic range (international normalized ratio, 2.0-3.0) for warfarin-treated patients was 44% (interquartile range, 23%-59%). The 1-year rates for major or clinically relevant nonmajor bleeding were 32% and 26% in apixaban and warfarin groups, respectively (hazard ratio, 1.20 [95% CI, 0.63-2.30]), whereas 1-year rates for stroke or systemic embolism were 3.0% and 3.3% in apixaban and warfarin groups, respectively. Death was the most common major event in the apixaban (21 patients [26%]) and warfarin (13 patients [18%]) arms. The pharmacokinetic substudy enrolled the target 50 patients. Median steady-state 12-hour area under the curve was 2475 ng/mL×h (10th to 90th percentiles, 1342-3285) for 5 mg of apixaban twice daily and 1269 ng/mL×h (10th to 90th percentiles, 615-1946) for 2.5 mg of apixaban twice daily. There was substantial overlap between minimum apixaban blood concentration, 12-hour area under the curve, and maximum apixaban blood concentration for patients with and without a major or clinically relevant nonmajor bleeding event.
Conclusions: There was inadequate power to draw any conclusion regarding rates of major or clinically relevant nonmajor bleeding comparing apixaban and warfarin in patients with AF and end-stage kidney disease on hemodialysis. Clinically relevant bleeding events were ≈10-fold more frequent than stroke or systemic embolism among this population on anticoagulation, highlighting the need for future randomized studies evaluating the risks versus benefits of anticoagulation among patients with AF and end-stage kidney disease on hemodialysis.
Registration: URL: https://www.
Clinicaltrials: gov; Unique identifier: NCT02942407.
Databáze: MEDLINE
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