Once versus twice daily direct oral anticoagulants in patients with recent stroke and atrial fibrillation

Abstract

Background: Data on the safety and effectiveness of once-daily (QD) versus twice-daily (BID) direct oral anticoagulants (DOAC) in comparison to vitamin K antagonists (VKA) and to one another in patients with atrial fibrillation (AF) and recent stroke are scarce. Patients and methods: Based on prospectively obtained data from the observational registry Novel-Oral-Anticoagulants-in-Ischemic-Stroke-Patients(NOACISP)-LONGTERM (NCT03826927) from Basel, Switzerland, we compared the occurrence of the primary outcome – the composite of recurrent ischemic stroke, major bleeding, and all-cause death – among consecutive AF patients treated with either VKA, QD DOAC, or BID DOAC following a recent stroke using Cox proportional hazards regression including adjustment for potential confounders. Results: We analyzed 956 patients (median age 80 years, 46% female), of whom 128 received VKA (13.4%), 264 QD DOAC (27.6%), and 564 BID DOAC (59%). Over a total follow-up of 1596 patient-years, both QD DOAC and BID DOAC showed a lower hazard for the composite outcome compared to VKA (adjusted HR [95% CI] 0.69 [0.48, 1.01] and 0.66 [0.47, 0.91], respectively). Upon direct comparison, the hazard for the composite outcome did not differ between patients treated with QD versus BID DOAC (adjusted HR [95% CI] 0.94 [0.70, 1.26]). Secondary analyses focusing on the individual components of the composite outcome revealed no clear differences in the risk-benefit profile of QD versus BID DOAC. Discussion and conclusion: The overall benefit of DOAC over VKA seems to apply to both QD and BID DOAC in AF patients with a recent stroke, without clear evidence that one DOAC dosing regimen is more advantageous than the other.

Atrial Fibrillation Detected before or after Stroke: Role of Anticoagulation

“…We used prospectively collected, individual patient data pooled within an established international collaboration of investigator‐initiated cohort studies of patients with AF and treatment with oral anticoagulants following a recent ischemic stroke or transient ischemic attack (TIA), as described previously. 8 , 14 , 15 , 16 , 17 , 18 This included 3 single‐center (Basel, Switzerland [NOACISP‐LONGTERM; NCT03826927]; 19 , 20 , 21 , 22 Erlangen, Germany; 23 , 24 Verona, Italy 25 ) and 2 multicenter cohorts (CROMIS‐2 [NCT02513316]; 26 , 27 SAMURAI‐NVAF [NCT01581502] 28 , 29 ).…”

“…The time origin for time‐to‐event analyses was the index ischemic event in all patients. We fitted both simple and multivariable models, the latter adjusted for common outcome‐modifying variables (ie, type of index event (stroke vs TIA), age, sex, CHA 2 DS 2 ‐VASc score (without the age and sex components, modified as in prior research 19 , 20 ), type of oral anticoagulation (DOAC or VKA) after index event, time to anticoagulant initiation, dyslipidemia, and eGFR), as in previous studies. 8 , 14 , 15 We imputed missing values in the covariates used in the adjusted models with simple imputation rules (ie, using the median for continuous variables and the mode [most frequent category] for categorical ones), and report the rate of missing values for all variables.…”

Update of Anticoagulation Use in Cardioembolic Stroke With a Special Reference to Endovascular Treatment

“…A recent systematic review and meta-analysis comparing the efficacy of NOACs versus VKAs within 1 week or within 2 weeks following AIS showed that treatment with NOACs was associated with significantly improved survival and reduced odds of HT and recurrent ischemic stroke compared to VKAs [ 22 ]. Overall benefit over VKAs seems to apply to both once-daily and twice-daily NOACs [ 23 ].…”

“…22 Overall benefit over VKAs seems to apply to both once-daily and twicedaily NOACs. 23 The evolution of guidelines 4 days after mild AIS and small infarct size (lesion ≤1.5 cm), 7 days after moderate stroke and medium infarct size, and 14 days after severe AIS and large infarct size. 10 The same recommendation was included as expert opinion statement in the ESO recommendations for secondary prevention of stroke and other thromboembolic events in patients with stroke or TIA and AF, suggesting antiplatelet therapy in the first 48 hours after AF-associated stroke.…”