Andrea Morotti, MD
Novel oral anticoagulants (NOACs) represent a valuable alternative to warfarin for embolism prevention in patients with non-valvular atrial fibrillation (AF). Multiple studies showed that NOACs use significantly reduces mortality compared to warfarin, with a lower risk of intracranial bleeding being the main mediator of this association.
Using a large National Insurance Database, Dr. Myung-Jin Cha and colleagues analyzed the risk of ischemic stroke, intracerebral hemorrhage (ICH), and all-cause mortality in Korean subjects with AF comparing NOACs versus warfarin users.
A total of 11611 NOACs users and 23262 on warfarin qualified for the analysis after CHA2DS2-VASc-based propensity score matching with a 1:2 ratio. The risk of ischemic/hemorrhagic stroke and death associated with warfarin versus NOACs treatment was investigated with time-to-event analysis.
The main result was that NOACs significantly lowered the odds of death (OR 0.70, 95% CI 0.59 – 0.81) and intracranial hemorrhage (OR 0.50, 95% CI 0.36 – 0.68) compared with warfarin treatment, confirming the findings observed in clinical trials and previous meta-analysis including non-Asian patients. When different NOACs were analyzed separately, Dabigatran and Apixaban were associated with lower risk of all-cause mortality in comparison with warfarin, whereas this was not the case for Rivaroxaban, as highlighted in Figure 3C (below). This observation was confirmed in sensitivity analyses including only oral anticoagulation-naïve patients and patients aged > 75. Interestingly, more than half of NOACs users were not prescribed a regular dose. Reduced dose NOACs therapy remained significantly associated with lower risk of all-cause death when compared with warfarin (OR 0.83, 95% CI 0.69 – 0.99).
Figure 3C. Crude cumulative incidence curve of all-cause mortality according to initiated treatment (warfarin vs. each non-vitamin K antagonist oral anticoagulant).
Some limitations should be kept in mind when interpreting this study. Patients with a history of ischemic or hemorrhagic stroke were excluded. Therefore, the safety profile of NOACs in the setting of secondary stroke prevention remains unclear. All the analyses were not adjusted for important factors that may influence the risk of bleeding, such as hemoglobin, hepatic and renal function, and blood pressure control.
In conclusion, this study confirmed the more favorable safety profile of NOACs compared with warfarin in terms of all-cause mortality. This finding remained significant in subgroups such as reduced dose NOACs users and elderly patients.
