Assistant Professor London School of Hygiene and Tropical Medicine London School of Hygiene & Tropical Medicine London, United Kingdom
Background: Direct oral anticoagulants (DOACs) have been reported to be associated with a higher risk of mortality compared with an older alternative, warfarin using primary care data in the UK. However, other studies observed contradictory findings and the duration of any potential effect is still unclear.
Objectives: Our primary objective was to evaluate the association between all-cause mortality and warfarin, compared with DOACs. Secondary objective was to investigate the duration of effect for this association.
Methods: A population-based cohort study was conducted using the data from the Hong Kong Clinical Data Analysis and Reporting System. Patients aged ≥18 years who initiated warfarin or a DOAC during the study period (01 Jan 2014-31 Dec 2019) were identified. Follow-up started from the first date of oral anticoagulant prescription and ended at earliest of the date of death, the day before drug switch (between warfarin and DOACs), or the end of study period. Demographics, comorbidities, co-medications and polypharmacy were considered as covariates for estimating the propensity score (PS). Cox proportional hazards regression model with PS-weighting was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).
Results: Among 66,363 oral anticoagulant users, 6,468/23,444 warfarin users and 5,880/42,919 DOACs users died during a median follow-up of 2.32 years (Interquartile range [IQR]: 3.23) and 1.63 years (IQR: 2.41), respectively. An increased risk of all-cause mortality was associated with warfarin (crude rate 110.15 per 1,000 person years) with a PS-weighted HR of 1.11 (95% CI 1.06-1.16), compared with DOACs (crude rate 69.55 per 1,000 person years). For duration of effect, no evidence supported a higher risk of all-cause mortality during 0-1 year comparing warfarin with DOACs (HR 1.03, 95% CI 0.96-1.11). However, increased risk of all-cause mortality was found comparing warfarin with DOACs (0-2 year: HR 1.09, 95% CI 1.03-1.15; 0-3 year; HR 1.10, 95% CI 1.04-1.15; 0-4 year: HR 1.10, 95% CI 1.05-1.16; 0-5 year: HR 1.11, 95% CI 1.06-1.16).
Conclusions: We observed a higher risk of all-cause mortality comparing warfarin with DOACs. However, as the higher risk was only observed one year after initiating an oral anticoagulant, it could be explained by between-person time-varying confounding between warfarin and DOACs users or a delayed onset. Further investigation for the cause specific mortality is needed to understand the underlying mechanism.
