Edoxaban versus Vitamin K Antagonist for Atrial Fibrillation after TAVR
Copyright © 2021 Massachusetts Medical Society..
BACKGROUND: The role of direct oral anticoagulants as compared with vitamin K antagonists for atrial fibrillation after successful transcatheter aortic-valve replacement (TAVR) has not been well studied.
METHODS: We conducted a multicenter, prospective, randomized, open-label, adjudicator-masked trial comparing edoxaban with vitamin K antagonists in patients with prevalent or incident atrial fibrillation as the indication for oral anticoagulation after successful TAVR. The primary efficacy outcome was a composite of adverse events consisting of death from any cause, myocardial infarction, ischemic stroke, systemic thromboembolism, valve thrombosis, or major bleeding. The primary safety outcome was major bleeding. On the basis of a hierarchical testing plan, the primary efficacy and safety outcomes were tested sequentially for noninferiority, with noninferiority of edoxaban established if the upper boundary of the 95% confidence interval for the hazard ratio did not exceed 1.38. Superiority testing of edoxaban for efficacy would follow if noninferiority and superiority were established for major bleeding.
RESULTS: A total of 1426 patients were enrolled (713 in each group). The mean age of the patients was 82.1 years, and 47.5% of the patients were women. Almost all the patients had atrial fibrillation before TAVR. The rate of the composite primary efficacy outcome was 17.3 per 100 person-years in the edoxaban group and 16.5 per 100 person-years in the vitamin K antagonist group (hazard ratio, 1.05; 95% confidence interval [CI], 0.85 to 1.31; P = 0.01 for noninferiority). Rates of major bleeding were 9.7 per 100 person-years and 7.0 per 100 person-years, respectively (hazard ratio, 1.40; 95% CI, 1.03 to 1.91; P = 0.93 for noninferiority); the difference between groups was mainly due to more gastrointestinal bleeding with edoxaban. Rates of death from any cause or stroke were 10.0 per 100 person-years in the edoxaban group and 11.7 per 100 person-years in the vitamin K antagonist group (hazard ratio, 0.85; 95% CI, 0.66 to 1.11).
CONCLUSIONS: In patients with mainly prevalent atrial fibrillation who underwent successful TAVR, edoxaban was noninferior to vitamin K antagonists as determined by a hazard ratio margin of 38% for a composite primary outcome of adverse clinical events. The incidence of major bleeding was higher with edoxaban than with vitamin K antagonists. (Funded by Daiichi Sankyo; ENVISAGE-TAVI AF ClinicalTrials.gov number, NCT02943785.).
| Errataetall: |
CommentIn: Ann Intern Med. 2022 Feb;175(2):JC22. - PMID 35099999 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:385 |
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| Enthalten in: |
The New England journal of medicine - 385(2021), 23 vom: 02. Dez., Seite 2150-2160 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Van Mieghem, Nicolas M [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 27.12.2021 Date Revised 13.04.2022 published: Print-Electronic ClinicalTrials.gov: NCT02943785 CommentIn: Ann Intern Med. 2022 Feb;175(2):JC22. - PMID 35099999 Citation Status MEDLINE |
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| doi: |
10.1056/NEJMoa2111016 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 100 | 1 | |a Van Mieghem, Nicolas M |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Edoxaban versus Vitamin K Antagonist for Atrial Fibrillation after TAVR |
| 264 | 1 | |c 2021 | |
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| 500 | |a Date Completed 27.12.2021 | ||
| 500 | |a Date Revised 13.04.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a ClinicalTrials.gov: NCT02943785 | ||
| 500 | |a CommentIn: Ann Intern Med. 2022 Feb;175(2):JC22. - PMID 35099999 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2021 Massachusetts Medical Society. | ||
| 520 | |a BACKGROUND: The role of direct oral anticoagulants as compared with vitamin K antagonists for atrial fibrillation after successful transcatheter aortic-valve replacement (TAVR) has not been well studied | ||
| 520 | |a METHODS: We conducted a multicenter, prospective, randomized, open-label, adjudicator-masked trial comparing edoxaban with vitamin K antagonists in patients with prevalent or incident atrial fibrillation as the indication for oral anticoagulation after successful TAVR. The primary efficacy outcome was a composite of adverse events consisting of death from any cause, myocardial infarction, ischemic stroke, systemic thromboembolism, valve thrombosis, or major bleeding. The primary safety outcome was major bleeding. On the basis of a hierarchical testing plan, the primary efficacy and safety outcomes were tested sequentially for noninferiority, with noninferiority of edoxaban established if the upper boundary of the 95% confidence interval for the hazard ratio did not exceed 1.38. Superiority testing of edoxaban for efficacy would follow if noninferiority and superiority were established for major bleeding | ||
| 520 | |a RESULTS: A total of 1426 patients were enrolled (713 in each group). The mean age of the patients was 82.1 years, and 47.5% of the patients were women. Almost all the patients had atrial fibrillation before TAVR. The rate of the composite primary efficacy outcome was 17.3 per 100 person-years in the edoxaban group and 16.5 per 100 person-years in the vitamin K antagonist group (hazard ratio, 1.05; 95% confidence interval [CI], 0.85 to 1.31; P = 0.01 for noninferiority). Rates of major bleeding were 9.7 per 100 person-years and 7.0 per 100 person-years, respectively (hazard ratio, 1.40; 95% CI, 1.03 to 1.91; P = 0.93 for noninferiority); the difference between groups was mainly due to more gastrointestinal bleeding with edoxaban. Rates of death from any cause or stroke were 10.0 per 100 person-years in the edoxaban group and 11.7 per 100 person-years in the vitamin K antagonist group (hazard ratio, 0.85; 95% CI, 0.66 to 1.11) | ||
| 520 | |a CONCLUSIONS: In patients with mainly prevalent atrial fibrillation who underwent successful TAVR, edoxaban was noninferior to vitamin K antagonists as determined by a hazard ratio margin of 38% for a composite primary outcome of adverse clinical events. The incidence of major bleeding was higher with edoxaban than with vitamin K antagonists. (Funded by Daiichi Sankyo; ENVISAGE-TAVI AF ClinicalTrials.gov number, NCT02943785.) | ||
| 650 | 4 | |a Comparative Study | |
| 650 | 4 | |a Equivalence Trial | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Multicenter Study | |
| 650 | 4 | |a Randomized Controlled Trial | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a 4-Hydroxycoumarins |2 NLM | |
| 650 | 7 | |a Anticoagulants |2 NLM | |
| 650 | 7 | |a Factor Xa Inhibitors |2 NLM | |
| 650 | 7 | |a Pyridines |2 NLM | |
| 650 | 7 | |a Thiazoles |2 NLM | |
| 650 | 7 | |a Vitamin K |2 NLM | |
| 650 | 7 | |a 12001-79-5 |2 NLM | |
| 650 | 7 | |a Phenindione |2 NLM | |
| 650 | 7 | |a 5M7Y6274ZE |2 NLM | |
| 650 | 7 | |a fluindione |2 NLM | |
| 650 | 7 | |a EQ35YMS20Q |2 NLM | |
| 650 | 7 | |a edoxaban |2 NLM | |
| 650 | 7 | |a NDU3J18APO |2 NLM | |
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| 700 | 1 | |a Hengstenberg, Christian |e verfasserin |4 aut | |
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| 700 | 1 | |a Lang, Irene |e verfasserin |4 aut | |
| 700 | 1 | |a Zamorano, José L |e verfasserin |4 aut | |
| 700 | 1 | |a Shawl, Fayaz |e verfasserin |4 aut | |
| 700 | 1 | |a Yamamoto, Masanori |e verfasserin |4 aut | |
| 700 | 1 | |a Watanabe, Yusuke |e verfasserin |4 aut | |
| 700 | 1 | |a Hayashida, Kentaro |e verfasserin |4 aut | |
| 700 | 1 | |a Hambrecht, Rainer |e verfasserin |4 aut | |
| 700 | 1 | |a Meincke, Felix |e verfasserin |4 aut | |
| 700 | 1 | |a Vranckx, Pascal |e verfasserin |4 aut | |
| 700 | 1 | |a Jin, James |e verfasserin |4 aut | |
| 700 | 1 | |a Boersma, Eric |e verfasserin |4 aut | |
| 700 | 1 | |a Rodés-Cabau, Josep |e verfasserin |4 aut | |
| 700 | 1 | |a Ohlmann, Patrick |e verfasserin |4 aut | |
| 700 | 1 | |a Capranzano, Piera |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, Hyo-Soo |e verfasserin |4 aut | |
| 700 | 1 | |a Pilgrim, Thomas |e verfasserin |4 aut | |
| 700 | 1 | |a Anderson, Richard |e verfasserin |4 aut | |
| 700 | 1 | |a Baber, Usman |e verfasserin |4 aut | |
| 700 | 1 | |a Duggal, Anil |e verfasserin |4 aut | |
| 700 | 1 | |a Laeis, Petra |e verfasserin |4 aut | |
| 700 | 1 | |a Lanz, Hans |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Cathy |e verfasserin |4 aut | |
| 700 | 1 | |a Valgimigli, Marco |e verfasserin |4 aut | |
| 700 | 1 | |a Veltkamp, Roland |e verfasserin |4 aut | |
| 700 | 1 | |a Saito, Shigeru |e verfasserin |4 aut | |
| 700 | 1 | |a Dangas, George D |e verfasserin |4 aut | |
| 700 | 0 | |a ENVISAGE-TAVI AF Investigators |e verfasserin |4 aut | |
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| 700 | 1 | |a van Mieghem, N |e investigator |4 oth | |
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| 700 | 1 | |a Veltkamp, R |e investigator |4 oth | |
| 700 | 1 | |a Vranckx, P |e investigator |4 oth | |
| 700 | 1 | |a Duggal, A |e investigator |4 oth | |
| 700 | 1 | |a Jin, J |e investigator |4 oth | |
| 700 | 1 | |a Laeis, P |e investigator |4 oth | |
| 700 | 1 | |a Gersh, B |e investigator |4 oth | |
| 700 | 1 | |a Bhatt, D |e investigator |4 oth | |
| 700 | 1 | |a Halperin, J |e investigator |4 oth | |
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| 700 | 1 | |a Weinberger, J |e investigator |4 oth | |
| 700 | 1 | |a Kaufman, D |e investigator |4 oth | |
| 700 | 1 | |a Milstein, M |e investigator |4 oth | |
| 700 | 1 | |a Lang, I |e investigator |4 oth | |
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| 700 | 1 | |a Mӧllmann, H |e investigator |4 oth | |
| 700 | 1 | |a Tamburino, C |e investigator |4 oth | |
| 700 | 1 | |a Hayashida, K |e investigator |4 oth | |
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| 700 | 1 | |a Kim, H-S |e investigator |4 oth | |
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| 700 | 1 | |a Nombela-Franco, L |e investigator |4 oth | |
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| 700 | 1 | |a Anderson, R |e investigator |4 oth | |
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