This study of data from UK general practices contributing to QResearch or Clinical Practice Research Datalink included 103,270 patients with and 92,791 without atrial fibrillation between 2011 and 2016. For both patients with- (adjusted hazard ratio 1.19, 95% confidence interval 1.09 to 1.29) and without atrial fibrillation (1.51, 1.38 to 1.66), the risk of mortality was increased in patients taking rivaroxaban compared with warfarin. Likewise for the apixaban cohort (1.14, 1.05 to 1.24, p=0.001).
The researchers conclude that these data provide reassurance about the safety of DOACs as an alternative to warfarin across all new incident users. They acknowledge that although many adjustments have been done using the data available on the existing databases, there is a possibility of unmeasured confounding or confounding by indication. They suggest that the increased all-cause mortality noted may reflect closer monitoring of patients undergoing treatment with warfarin or unmeasured confounding due to prescribing choices related to underlying comorbidities.