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      Clinical Effectiveness of Direct Oral Anticoagulants vs Warfarin in Older Patients With Atrial Fibrillation and Ischemic Stroke : Findings From the Patient-Centered Research Into Outcomes Stroke Patients Prefer and Effectiveness Research (PROSPER) Study

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          Abstract

          Is direct oral anticoagulant a better option than warfarin for secondary prevention in older survivors of ischemic stroke who have atrial fibrillation? In this observational study of 11 662 patients with atrial fibrillation who had had an ischemic stroke and were anticoagulation naive, patients discharged while receiving direct oral anticoagulants had more days at home postdischarge and were less likely to experience major adverse cardiovascular events, all-cause mortality, all-cause readmissions, cardiovascular readmissions, or hemorrhagic strokes, despite a small but significant increase in gastrointestinal bleeding. Direct oral anticoagulants appear to be an effective and safe treatment option compared with warfarin for patients with atrial fibrillation who have ischemic stroke. This cohort assesses the clinical effectiveness of direct oral anticoagulants vs warfarin for stroke prevention in patients with atrial fibrillation. Current guidelines recommend direct oral anticoagulants (DOACs) over warfarin for stroke prevention in patients with atrial fibrillation (AF) who are at high risk. Despite demonstrated efficacy in clinical trials, real-world data of DOACs vs warfarin for secondary prevention in patients with ischemic stroke are largely based on administrative claims or have not focused on patient-centered outcomes. To examine the clinical effectiveness of DOACs (dabigatran, rivaroxaban, or apixaban) vs warfarin after ischemic stroke in patients with AF. This cohort study included patients who were 65 years or older, had AF, were anticoagulation naive, and were discharged from 1041 Get With The Guidelines–Stroke–associated hospitals for acute ischemic stroke between October 2011 and December 2014. Data were linked to Medicare claims for long-term outcomes (up to December 2015). Analyses were completed in July 2018. DOACs vs warfarin prescription at discharge. The primary outcomes were home time, a patient-centered measure defined as the total number of days free from death and institutional care after discharge, and major adverse cardiovascular events. A propensity score–overlap weighting method was used to account for differences in observed characteristics between groups. Of 11 662 survivors of acute ischemic stroke (median [interquartile range] age, 80 [74-86] years), 4041 (34.7%) were discharged with DOACs and 7621 with warfarin. Except for National Institutes of Health Stroke Scale scores (median [interquartile range], 4 [1-9] vs 5 [2-11]), baseline characteristics were similar between groups. Patients discharged with DOACs (vs warfarin) had more days at home (mean [SD], 287.2 [114.7] vs 263.0 [127.3] days; adjusted difference, 15.6 [99% CI, 9.0-22.1] days) during the first year postdischarge and were less likely to experience major adverse cardiovascular events (adjusted hazard ratio [aHR], 0.89 [99% CI, 0.83-0.96]). Also, in patients receiving DOACs, there were fewer deaths (aHR, 0.88 [95% CI, 0.82-0.95]; P  < .001), all-cause readmissions (aHR, 0.93 [95% CI, 0.88-0.97]; P  = .003), cardiovascular readmissions (aHR, 0.92 [95% CI, 0.86-0.99]; P  = .02), hemorrhagic strokes (aHR, 0.69 [95% CI, 0.50-0.95]; P  = .02), and hospitalizations with bleeding (aHR, 0.89 [95% CI, 0.81-0.97]; P  = .009) but a higher risk of gastrointestinal bleeding (aHR, 1.14 [95% CI, 1.01-1.30]; P  = .03). In patients with acute ischemic stroke and AF, DOAC use at discharge was associated with better long-term outcomes relative to warfarin.

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          Get With the Guidelines-Stroke is associated with sustained improvement in care for patients hospitalized with acute stroke or transient ischemic attack.

          Adherence to evidence-based guidelines for treatment of stroke or transient ischemic attack is suboptimal. We sought to establish whether participation in Get With the Guidelines-Stroke was associated with improvements in adherence. This prospective, nonrandomized, national quality improvement program measured adherence to guideline recommendations in 322 847 hospitalized patients discharged with a diagnosis of ischemic stroke or transient ischemic attack. A volunteer sample of 790 US academic and community hospitals participated from 2003 through 2007. The main outcome measures were change in adherence over time to 7 prespecified performance measures and a composite measure (total number of interventions provided in eligible patients divided by total number of care opportunities among eligible patients). Generalized estimating equations were used to identify factors associated with improvement. Participation in Get With the Guidelines-Stroke was associated with improvements in the 7 individual and 1 composite measures from baseline to the fifth year: intravenous thrombolytics (42.09% versus 72.84%), early antithrombotics (91.46% versus 97.04%), deep vein thrombosis prophylaxis (73.79% versus 89.54%), discharge antithrombotics (95.68% versus 98.88%), anticoagulation for atrial fibrillation (95.03% versus 98.39%), lipid treatment for low-density lipoprotein >100 mg/dL (73.63% versus 88.29%), smoking cessation (65.21% versus 93.61%), and composite (83.52% versus 93.97%) (P<0.0001 for all comparisons). Multivariate analysis showed that time in Get With the Guidelines-Stroke was associated with a 1.18-fold yearly increase in the odds of fulfilling care opportunities that was independent of secular trends. Get With the Guidelines-Stroke participation was associated with increased adherence to all stroke performance measures. Markedly improved stroke care was seen in all hospitals regardless of size, geography, and teaching status.
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            Balancing Covariates via Propensity Score Weighting

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              Effectiveness and safety of reduced dose non-vitamin K antagonist oral anticoagulants and warfarin in patients with atrial fibrillation: propensity weighted nationwide cohort study

              Objective To examine clinical effectiveness and safety of apixaban 2.5 mg, dabigatran 110 mg, and rivaroxaban 15 mg compared with warfarin among patients with atrial fibrillation who had not previously taken an oral anticoagulant. Design Propensity weighted (inverse probability of treatment weighted) nationwide cohort study. Setting Individual linked data from three nationwide registries in Denmark. Participants Patients with non-valvular atrial fibrillation filling a first prescription for an oral anticoagulant from August 2011 to February 2016. Patients who filled a prescription for a standard dose non-vitamin K antagonist oral anticoagulant (novel oral anticoagulants, NOACs) were excluded. To control for baseline differences in the population, a propensity score for receipt of either of the four treatment alternatives was calculated to apply an inverse probability treatment weight. Intervention Initiated anticoagulant treatment (dabigatran 110 mg, rivaroxaban 15 mg, apixaban 2.5 mg, and warfarin). Main outcome measures Patients were followed in the registries from onset of treatment for the primary effectiveness outcome of ischaemic stroke/systemic embolism and for the principal safety outcome of any bleeding events. Results Among 55 644 patients with atrial fibrillation who met inclusion criteria, the cohort was distributed according to treatment: apixaban n=4400; dabigatran n=8875; rivaroxaban n=3476; warfarin n=38 893. The overall mean age was 73.9 (SD 12.7), ranging from a mean of 71.0 (warfarin) to 83.9 (apixaban). During one year of follow-up, apixaban was associated with higher (weighted) event rate of ischaemic stroke/systemic embolism (4.8%), while dabigatran, rivaroxaban, and warfarin had event rates of 3.3%, 3.5%, and 3.7%, respectively. In the comparison between a non-vitamin K antagonist oral anticoagulant and warfarin in the inverse probability of treatment weighted analyses and investigation of the effectiveness outcome, the hazard ratios were 1.19 (95% confidence interval 0.95 to 1.49) for apixaban, 0.89 (0.77 to 1.03) for dabigatran, and 0.89 (0.69 to 1.16) for rivaroxaban. For the principal safety outcome versus warfarin, the hazard ratios were 0.96 (0.73 to 1.27) for apixaban, 0.80 (0.70 to 0.92) for dabigatran, and 1.06 (0.87 to 1.29) for rivaroxaban. Conclusion In this propensity weighted nationwide study of reduced dose non-vitamin K antagonist oral anticoagulant regimens, apixaban 2.5 mg twice a day was associated with a trend towards higher rates of ischaemic stroke/systemic embolism compared with warfarin, while rivaroxaban 15 mg once a day and dabigatran 110 mg twice a day showed a trend towards lower thromboembolic rates. The results were not significantly different. Rates of bleeding (the principal safety outcome) were significantly lower for dabigatran, but not significantly different for apixaban and rivaroxaban compared with warfarin.
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                Author and article information

                Journal
                JAMA Neurology
                JAMA Neurol
                American Medical Association (AMA)
                2168-6149
                July 22 2019
                Affiliations
                [1 ]Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina
                [2 ]Department of Neurology, Duke University Medical Center, Durham, North Carolina
                [3 ]Division of Cardiology, University of California, Los Angeles
                [4 ]University of Texas Southwestern, Dallas
                [5 ]Harvard Medical School, Massachusetts General Hospital, Boston
                [6 ]Brigham and Women’s Hospital Heart & Vascular Center, Harvard Medical School, Boston, Massachusetts
                [7 ]Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada
                [8 ]Patient-Centered Research Into Outcomes Stroke Patients Prefer and Effectiveness Research Study, Durham, North Carolina
                Article
                10.1001/jamaneurol.2019.2099
                6647003
                31329212
                6035f120-52ad-4226-bc16-567f25e170f8
                © 2019
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