Oral Anticoagulants in Atrial Fibrillation Patients With Recent Stroke Who Are Dependent on the Daily Help of Others

Abstract

Background and Purpose: Data on the effectiveness and safety of direct oral anticoagulants (DOACs) versus vitamin K antagonists (VKAs) in patients with stroke attributable to atrial fibrillation (AF) who were dependent on the daily help of others at hospital discharge are scarce. Methods: Based on prospectively obtained data from the observational Novel-Oral-Anticoagulants-in-Ischemic-Stroke-Patients-longterm registry 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 patients with AF-stroke treated with either VKAs or DOACs between patients dependent (defined as modified Rankin Scale score, 3–5) and patients independent at discharge. We used simple, adjusted, and weighted Cox proportional hazards regression to account for potential confounders. Results: We analyzed 801 patients (median age 80 years, 46% female), of whom 391 (49%) were dependent at discharge and 680 (85%) received DOACs. Over a total follow-up of 1216 patient-years, DOAC- compared to VKA-treated patients had a lower hazard for the composite outcome (hazard ratio [HR], 0.58 [95% CI, 0.42–0.81]), as did independent compared to dependent patients (HR, 0.54 [95% CI, 0.40–0.71]). There was no evidence that the effect of anticoagulant type (DOAC versus VKA) on the hazard for the composite outcome differed between dependent (HR dependent , 0.68 [95% CI, 0.45–1.01]) and independent patients (HR independent , 0.44 [95% CI, 0.26–0.75]) in the simple model ( P interaction =0.212). Adjusted (HR dependent , 0.74 [95% CI, 0.49–1.11] and HR independent , 0.51 [95% CI, 0.30–0.87]; P interaction =0.284) and weighted models (HR dependent , 0.79 [95% CI, 0.48–1.31] and HR independent , 0.46 [95% CI, 0.26–0.81]; P interaction =0.163) yielded concordant results. Secondary analyses focusing on the individual components of the composite outcome were consistent to the primary analyses. Conclusions: The benefits of DOACs in patients with atrial fibrillation with a recent stroke were maintained among patients who were dependent on the help of others at discharge. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03826927.

Oral Anticoagulants in the Oldest Old with Recent Stroke and Atrial Fibrillation

“…We used prospectively collected, individual patient data pooled from an established international collaboration of investigator‐initiated cohort studies of patients with AF, recent ischemic stroke or transient ischemic attack (TIA) and OAC treatment, as described previously. 15 This included 3 single‐center (Basel, Switzerland [NOACISP‐LONGTERM; NCT03826927] 16 ; Erlangen, Germany 17 ; Verona, Italy 18 ) and four multicenter cohorts (CROMIS‐2 [NCT02513316] 19 ; RAF 20 ; RAF‐DOAC 21 ; SAMURAI‐NVAF [NCT01581502] 22 , 23 ). The number of patients contributed by each cohort, as well as the recruitment period and follow‐up duration are summarized in Table S1 .…”

“…In this study, we included consecutive patients with (1) an index recent (ie, <3 months) ischemic stroke or TIA (as defined previously 15 ); (2) nonvalvular AF (either known before index event or first diagnosed thereafter); (3) treatment with DOAC [ie, apixaban, dabigatran, edoxaban, rivaroxaban] or VKA [ie, phenprocoumon, warfarin], initiated within 3 months after the index event; and (4) prospectively ascertained follow‐up data for at least 3 months after the index event for the outcomes recurrent ischemic stroke, ICH and all‐cause death, defined as reported previously. 15 , 16 We excluded patients with missing follow‐up or information on age, those with OAC initiation >3 months or unknown, and those with outcome events occurring before OAC initiation.…”

“…Follow‐up data included length of follow‐up and absence or occurrence and timing of any of the following outcome events, which were defined in line with prior research 15 , 16 : (1) recurrent ischemic stroke (defined as new neurological deficits with a corresponding finding on neuroimaging); (2) ICH (defined as new neurological deficits with detection of intracranial bleeding on neuroimaging); and (3) all‐cause death, defined as every death irrespective of the cause and regardless of whether the cause was known or not.…”

“…The primary outcome was the time to occurrence of the composite of recurrent ischemic stroke, ICH and all‐cause death, in accordance with prior research. 15 , 16 Secondary outcomes were the time to occurrence of each of these outcomes separately.…”

“…We fitted the model three times according to the predefined analysis plan: (i) simple model including type of OAC and dichotomized age, with and without interaction term; (ii) adjusted model taking into account the known prognostic importance of sex, NIHSS at baseline and CHA 2 DS 2 ‐VASc score 24 (without the age and sex components, modified as in prior research 16 ); (iii) weighted model, using the stabilized inverse probability of treatment weights (SIPTW). 26 We constructed comparable treatment groups (DOAC vs. VKA) with regard to the following potentially outcome‐modifying variables, as in previous research 15 , 16 : sex, NIHSS at baseline, diabetes mellitus, hypertension, dyslipidemia, eGFR, history of prior stroke or TIA, history of ICH, current smoking, concomitant antiplatelet use and cohort study. We calculated the SIPTW using logistic regression and used robust standard errors for the 95% confidence intervals (CI) and p‐values of the weighted analysis.…”