Time-to-event comparative effectiveness of NOACs vs VKAs in newly diagnosed non-valvular atrial fibrillation patients

A bstract Objective To investigate the difference in the time-to-event probabilities of ischaemic events, major bleeding and death of NOAC vs VKAs in newly diagnosed non-valvular atrial fibrillation patients. Design Retrospective observational cohort study. Setting UK’s Clinical Practice Research Data linked to the Hospital Episode Statistics inpatient and outpatient data, mortality data and the Patient Level Index of Multiple Deprivation. Participants Patients over 18 years of age, with an initial diagnosis of atrial fibrillation between 1st-Mar-2011 and 31-July-2017, without a record for a valve condition, prosthesis or procedure previous to initial diagnosis, and without a record of oral anticoagulant treatment in the previous year. Intervention Oral anticoagulant treatment with either vitamin K antagonists (VKAs) or the newer target-specific oral anticoagulants (NOACs). Main Outcome Measures Ischaemic event, major bleeding event and death from 15 days from initial prescription up to two years follow-up. Statistical Analysis Treatment effect was defined as the difference in time-to-event probability between NOAC and VKA treatment groups. Treatment and outcomes were modelled using an ensemble of parametric and non-parametric models, and the average and conditional average treatment effects were estimated using one-step Targeted Maximum Likelihood Estimation (TMLE). Heterogeneity of treatment effect was examined using variable importance methods in Bayesian Additive Regression Trees (BART). Results The average treatment effect of NOAC vs VKA was consistently close to zero across all times, with a temporal average of 0.00[95%0.00, 0.00] for ischaemic event, 0.00%[95% − 0.01, 0.01] for major bleeding and 0.00[95% − 0.01, 0.01] for death. Only history of major bleeding was found to influence the distribution of treatment effect for major bleeding, but its impact on the associated conditional average treatment effect was not significant. Conclusions This study found no statistically significant difference between NOAC and VKA users up to two years of medication use for the prevention of ischaemic events, major bleeding or death.