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Aims The aim of this study was to determine the comparative effectiveness and safety of direct oral anticoagulants (DOACs) and warfarin in adults with atrial fibrillation (AF) by level of kidney function. Methods and results We pooled findings from 5 retrospective cohorts (2011–2018) across Australia and Canada of adults with; a new dispensation for a DOAC or warfarin, an AF diagnosis, and a measure of baseline estimated glomerular filtration rate (eGFR). The outcomes of interest, within 1 year from the cohort entry date, were: (1) the composite of all-cause death, first hospitalization for ischemic stroke, or transient ischaemic attack (effectiveness), and (2) first hospitalization for major bleeding defined as an intracranial, upper or lower gastrointestinal, or other bleeding (safety). Cox models were used to examine the association of a DOAC versus warfarin with outcomes, after 1:1 matching via a propensity score. Kidney function was categorized as eGFR ≥60, 45-59, 30-44, and <30 mL/min/1.73m2. A total of 74,542 patients were included in the matched analysis. DOAC initiation was associated with greater or similar effectiveness compared to warfarin initiation across all eGFR categories (pooled HRs[95% CIs] for eGFR categories: 0.74[0.69-0.79], 0.76[0.54-1.07], 0.68[0.61-0.75] and 0.86[0.76-0.98]), respectively. DOAC initiation was associated with lower or similar risk of major bleeding than warfarin initiation (pooled HRs[95% CIs]: 0.75[0.65-0.86], 0.81[0.65-1.01], 0.82[0.66-1.02], and 0.71[0.52-0.99], respectively). Associations between DOAC initiation, compared with warfarin initiation, and study outcomes were not modified by eGFR category. Conclusion DOAC use, compared with warfarin use, was associated with lower or similar risk of all-cause death, ischemic stroke and transient ischemic attack and also a lower or similar risk of major bleeding across all levels of kidney function.

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Introduction Several jurisdictions have adopted a more conservative approach to anemia in patients receiving dialysis amid safety concerns from target hemoglobin studies. It is largely unknown if this has contributed to a change in clinical outcomes. Methods A national registry was used to identify 35,945 adult patients who initiated and were maintained on dialysis for ≥90 days in Canada from January 2007 to December 2015. Outcomes were ascertained until March 2017 via linkage with hospital discharge diagnoses. Cox proportional hazards models were used to investigate the association between the era of dialysis initiation and the primary composite outcome (acute myocardial infarction [AMI], stroke, or mortality). Results The mean hemoglobin at dialysis initiation decreased from 102.9 g/l in 2007 to 95.5 g/l in 2015, corresponding with a higher prevalence of hemoglobin <80 g/l (8% to 17%) and a reduction in erythropoiesis stimulating agent (ESA) use (49% to 44%). After multivariable adjustment, Era 3 (2013–2015) was associated with an 8% relative risk reduction in the primary outcome compared with Era 1 (2007–2009) (hazard ratio [HR] 0.92, 95% confidence interval [CI] 0.88–0.96), a 10% relative reduction in mortality (HR 0.90, 95% CI 0.85–0.94) but no significant change in AMI or stroke. In a model without era, neither hemoglobin nor ESA use was an independent predictor of outcome. Conclusion There have been modest declines in average hemoglobin values and ESA use among incident dialysis patients in Canada with no change in major cardiovascular outcomes. Patient survival has improved over time, likely for reasons other than anemia management.