Assistant professor College of pharmacy and Institute of pharmaceutical science and technology, hanyang university, Republic of Korea
Background: The dose of each direct-acting oral anticoagulant (DOAC) is adjusted according to its criteria based on the results of clinical trials. However, whether dose adjustment regimens are appropriate in actual clinical practice is uncertain.
Objectives: This study aims to evaluate the appropriateness of dose adjustment by comparing the effectiveness of patients taking DOAC versus warfarin through a systematic review and network meta-analysis.
Methods: The studies included in the network meta-analysis were retrieved from MEDLINE, EMBASE, and CENTRAL until August 2022. Primary outcomes were the incidence of stroke/systemic embolisms (S/SE) and major bleeding. The implementation and reporting of systematic literature reviews followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. This study protocol was registered at the International Platform of Registered Systematic Review and Meta-Analysis Protocols (registration number INPLASY202280073). The effect sizes were expressed as hazard ratio (HR) with 95% CI. A bayesian network model were constructed based on the Markov chain Monte Carlo (MCMC) operation and a rank probability was used evaluate the most effective treatment.
Results: A total of 26 studies with 1,898,992 patients were eligible for this analysis. In direct comparison with warfarin, the incidence of S/SE was significantly lower in patients with taking apixaban 5 mg (HR, 0.77; 95% CI, 0.69-0.87), dabigatran 150 mg (HR, 0.84; 95% CI, 0.76-0.93), dabigatran 110 mg (HR, 0.82; 95% CI, 0.71-0.95), rivaroxaban 20 mg (HR, 0.82; 95% CI, 0.75-0.90), rivaroxaban 15 mg (HR, 0.84; 95% CI, 0.72-0.98), and edoxaban 60 mg (HR, 0.65; 95% CI, 0.45-0.93). Apixaban 2.5 mg and edoxaban 30 mg had no statistically significant difference from warfarin in S/SE incidence. In a rank order of effectiveness based on probability, edoxaban 60 mg had the best score. Major bleeding occurred more frequently in patients taking warfarin than in those apixaban 5 mg (HR, 0.63; 95% CI, 0.57-0.70), apixaban 2.5 mg (HR, 0.66; 95% CI, 0.58-0.74), dabigatran 150 mg (HR, 0.75; 95% CI, 0.69-0.81), dabigatran 110 mg (HR, 0.74; 95% CI, 0.64-0.87), edoxaban 60 mg (HR, 0.59; 95% CI, 0.37-0.97) and edoxaban 30 mg (HR, 0.58; 95% CI, 0.51-0.65). In the rank analysis of major bleeding, edoxaban 30 mg was the first-ranking treatment.
Conclusions: This network meta-analysis showed that low and standard doses of all DOACs for S/SE prevention in patients with non-valvular atrial fibrillation have favorable risk-benefit profile. All DOACs other than apixaban 2.5mg and edoxaban 30mg had parallel effectiveness with respect to S/SE prevention.
