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Joosten, L.P.T.; Doorn, S. van; Ven, P.M. van de; Köhlen, B.T.G.; Nierman, M.C.; Koek, H.L.; ... ; Geersing, G.J. (2024)

Safety of switching from a vitamin K antagonist to a non-vitamin K antagonist oral anticoagulant in frail older patients with atrial fibrillation: results of the FRAIL-AF randomized controlled trial

Article / Letter to editor
Background: There is ambiguity whether frail patients with atrial fibrillation (AF) managed with vitamin K antagonists (VKAs) should be switched to a non-vitamin K oral anticoagulant (NOAC).Methods: We conducted a pragmatic, multicenter, open-label, randomized controlled superiority trial. Older AF patients living with frailty (age >= 75 years plus a Groningen Frailty Indicator (GFI) score >= 3) were randomized to switch from INR-guided VKA treatment to a NOAC or to continued VKA treatment. Patients with a glomerular filtration rate <30 mLmin(-1)1.73 m(-2) or with valvular AF were excluded. Follow-up was 12 months. The cause-specific hazard ratio (HR) was calculated for occurrence of the primary outcome which was a major or clinically relevant non-major bleeding complication, whichever came first, accounting for death as a competing risk. Analyses followed the intention-to-treat principle. Secondary outcomes included thromboembolic events.Results: Between January 2018 and June 2022,...Show moreBackground: There is ambiguity whether frail patients with atrial fibrillation (AF) managed with vitamin K antagonists (VKAs) should be switched to a non-vitamin K oral anticoagulant (NOAC).Methods: We conducted a pragmatic, multicenter, open-label, randomized controlled superiority trial. Older AF patients living with frailty (age >= 75 years plus a Groningen Frailty Indicator (GFI) score >= 3) were randomized to switch from INR-guided VKA treatment to a NOAC or to continued VKA treatment. Patients with a glomerular filtration rate <30 mLmin(-1)1.73 m(-2) or with valvular AF were excluded. Follow-up was 12 months. The cause-specific hazard ratio (HR) was calculated for occurrence of the primary outcome which was a major or clinically relevant non-major bleeding complication, whichever came first, accounting for death as a competing risk. Analyses followed the intention-to-treat principle. Secondary outcomes included thromboembolic events.Results: Between January 2018 and June 2022, a total of 2,621 patients were screened for eligibility and 1,330 patients were randomized (mean age 83 years, median GFI 4). After randomization 6 patients in the switch to NOAC arm and 1 patient in the continue with VKA arm were excluded due to the presence of exclusion criteria, leaving 662 patients switched from a VKA to a NOAC and 661 patients continued VKAs in the intention-to-treat population. After 163 primary outcome events (101 in the switch arm, 62 in the continue arm), the trial was stopped for futility according to a prespecified futility analysis. The HR for our primary outcome was 1.69 (95% CI 1.23-2.32). The HR for thromboembolic events was 1.26 (95% CI 0.60 to 2.61).Conclusions: Switching INR-guided VKA treatment to a NOAC in frail older patients with AF was associated with more bleeding complications compared to continuing VKA treatment, without an associated reduction in thromboembolic complications.Show less
anticoagulants
atrial fibrillation
frail elderly
vitamin K
All authors
Joosten, L.P.T.; Doorn, S. van; Ven, P.M. van de; Köhlen, B.T.G.; Nierman, M.C.; Koek, H.L.; Hemels, M.E.W.; Huisman, M.V.; Kruip, M.; Faber, L.M.; Wiersma, N.M.; Buding, W.F.; Fijnheer, R.; Adriaansen, H.J.; Roes, K.C.; Hoes, A.W.; Rutten, F.H.; Geersing, G.J.
Date
2024-01-23
Journal
Circulation
Volume
149
Issue
4
Pages
279 - 289
DOI
doi:10.1161/CIRCULATIONAHA.123.066485