DOAC use in patients with atrial fibrillation may also preserve brain health

For patients with atrial fibrillation (AF), the use of a direct-acting oral anticoagulant (DOAC) may confer additional benefits by reducing the incidence of dementia relative to warfarin treatment or nonuse of any anticoagulant, as shown in a study.

In propensity-matched analyses, any oral anticoagulant (OAC) use reduced the risk of developing dementia by about 40 percent compared with nonuse (hazard ratio [HR], 0.59, 95 percent confidence interval [CI], 0.44–0.80; p<0.001). [J Am Heart Assoc 2022;doi:10.1161/JAHA.121.023098]

When stratified by OAC type, exclusive DOAC use halved the risk of dementia relative to the use of either a non-OAC (HR, 0.49, 95 percent CI, 0.33–0.73; p<0.001) or warfarin (HR, 0.46, 95 percent CI, 0.28–0.74; p=0.002). There was no significant difference in the risk of new-onset dementia between warfarin and non‐OAC use (HR, 1.08, 95 percent CI, 0.70–1.70; p=0.723).

“Our findings are in line with a previous study … that used two US databases and reported that DOACs significantly lowered the incidence of dementia compared with warfarin (meta‐analysed HRs were 0.85 [95 percent CI, 0.71–1.01] with dabigatran; 0.85 [95 percent CI, 0.76–0.94] with rivaroxaban; and 0.80 [95 percent CI, 0.65–0.97] with apixaban),” according to the investigators. [J Am Heart Assoc 2018;7:e009561]

Why patients receiving warfarin had a higher risk of dementia could be attributed to the difficulty in managing the time in therapeutic range for the international normalized ratio, they pointed out.

“Time outside the therapeutic range in these patients can lead to microemboli and microbleeds, which could cause chronic cerebral injury and finally lead to dementia. However, according to a recent meta‐analysis … even patients who achieve a high time in therapeutic range (>66 percent) while taking warfarin are at increased risk of intracranial bleeding when compared with patients receiving a DOAC,” the investigators noted. [Heart Rhythm 2014;11:2206-2213; Am J Cardiol 2020;doi:10.1016/j.amjcard.2020.10.064]

Taken together, data from previous studies and the present findings suggest that the use of DOACs may be a promising approach to reduce the risk of dementia in patients with AF, they said. 

However, the investigators advised caution when interpreting the protective effect of DOAC therapy against dementia, given the study’s relatively short mean follow‐up (3.7 years).

The study was based on a large Australian national primary care data set and involved 18,813 AF patients (mean age 71.9 years, 47.1 percent women), among whom 425 (2.3 percent) developed new-onset dementia. A total of 11,419 patients who had a recorded OAC prescription for at least 80 percent of their follow‐up time were included in the analyses.

“We performed a sensitivity analysis to evaluate the potential bias associated with [the exclusion of patients who received an OAC for <80 percent of their follow‐up period] using cohorts constructed regardless of treatment duration. The findings were similar to the primary analysis, and any bias related to this exclusion was minimal,” the investigators said.

“We assumed that patients who had recorded OAC prescriptions were taking their medication as directed during follow‐up. We did not have data on actual adherence with therapy,” they added.