Lower dose direct oral anticoagulation or warfarin in atrial fibrillation. Which one is the best when time on therapeutic range information is available?

FUNDING ACKNOWLEDGEMENTS: Type of funding sources: Public hospital(s). Main funding source(s): Helsinki and Uusimaa Hospital District (TYH2019309) and The Finnish Foundation for Cardiovascular Research BACKGROUND AND AIMS: Elderly patients with atrial fibrillation (AF) and patients with renal failure – for example – are recommended to use reduced doses of direct oral anticoagulants (DOACs) to minimize risk of ischemic stroke and hemorrhagic complications. However, it is not known whether DOACs used with reduced doses are better than warfarin when the quality of warfarin treatment is available by means of time in therapeutic range (TTR). METHODS: The Finnish AntiCoagulation in Atrial Fibrillation (FinACAF) is a nationwide study of AF patients that combines data from several Finnish health care registers. Here all new-onset AF patients from 2011 to 2018 on reduced dose DOAC in Finland and patients on warfarin with TTR data were analyzed. Comorbidities, concomitant medications and CHA2DS2-VASc -scores were recorded until date of AF diagnosis. OAC purchases from diagnosis of AF to the end of study were analyzed. ICD-10 diagnoses for stroke (ischemic or hemorrhagic) or transient ischemic attack during OAC-use were analyzed until maximum follow-up of 730 days. Crude rates of stroke as well as weighted rates are provided. To avoid confounding by baseline characteristics as well as medications, an inverse probability of treatment weighted analysis was made. For warfarin users with sufficient laboratory data, time in therapeutic range (TTR) was calculated and patient quartiles by TTR were assigned. RESULTS: Altogether, 52 204 new-onset AF patients with OAC therapy (46.1 % male, mean age 75.7 years, 43 549 on warfarin - with mean TTR 66%, median TTR 72%) were followed for 91 549 patient-years (py). Rate of stroke among patients on lower dose DOACs was 5.2/100 patient years (py) for dabigatran (n=2 672), 4.3/100 py for apixaban (n=3 936), 3.9 /100 py for rivaroxaban (n=1 866). In the TTR-quartiles of patients on warfarin, the rates of stroke were 9.3, 7.2, 5.5 and 4.3 /100 py from the lowest (mean TTR 32%) to the highest quartile (mean TTR 90%), respectively. The weighted rates of stroke were 5.1, 3.5 and 3.1/100 py for dabigatran, apixaban and rivaroxaban, respectively and for warfarin from the lowest to the highest quartile: 8.7, 7.0, 5.4 and 4.1/100 py. Figure provides survival probabilities of the OAC groups with confidence limits. CONCLUSION: In AF patients treated with OAC, the rates of stroke were highest among patients on warfarin at the lowest TTR quartiles, while the differences between high TTR groups and lower dose DOACs were only modest. [Figure: see text]