Abstract
Background
Several previous studies reported anti-inflammatory effect of direct oral anticoagulant (DOAC). However, it was limited to basic pathological data with small sample size. Real-world large clinical data is still scarce.
Methods
We conducted a single-center prospective observational registry of NVAF patients treated with DOACs: the DIRECT registry (UMINehz745.034333283). All patients with nonvalvular atrial fibrillation (NVAF) (N=2216) who were users of dabigatran (N=648), rivaroxaban (N=538), apixaban (N=599), or edoxaban (N=431) from June 2011 to November 2017 were enrolled (71.6±10.8 years, 36.4% female, follow-up duration: 407.2±388.3 days). High sensitive C-reactive protein (hsCRP) test was performed before (within 3 months from the start) and after the start of DOAC prescription (6±3 months after the start). Patients with a hsCRP value >1.00 mg/dL were excluded from the analysis due to possibility of other systemic inflammatory conditions. The present post-hoc study of the DIRECT registry assessed anti-inflammatory effect of DOAC. Pre-hsCRP and post-hsCRP were compared by Wilcoxon Signed Ranks test.
Results
A total of 1,855 patients were analyzed in the present study (71.0±10.7 years, 677/1,855 (36%) females). In the overall cohort, hsCRP significantly decreased after the start of DOAC prescription (pre median 0.08 interquartile range [0.04–0.17] mg/dL vs. post 0.06 [0.03–0.12] mg/dL, p<0.001). The significant reduction of hsCRP was consistent across all DOACs (p=0.301) [dabigatran (N=562), pre 0.08 [0.04–0.1625] mg/dL vs. post 0.06 [0.03–0.12] mg/dL, p<0.001: rivaroxaban (N=457), pre 0.07 [0.04–0.16] mg/dL vs. post 0.07 [0.03–0.125] mg/dL, p<0.001: apixaban (N=494), pre 0.09 [0.04–0.19] mg/dL vs. post 0.06 [0.03–0.13] mg/dL, p<0.001: edoxaban (N=342), pre 0.08 [0.04–0.19] mg/dL vs. post 0.06 [0.03–0.13] mg/dL, p<0.001].
Conclusions
The present study of DIRECT registry suggested anti-inflammatory effect of DOAC presented as a significant reduction of hsCRP. Although further investigation would be warranted to evaluate the clinical significance of the suppressed systemic inflammation, the recent favorable clinical data of DOACs might be attributed to the present finding.