New Oral Anticoagulants and the Risk of Intracranial Hemorrhage: Traditional and Bayesian Meta-analysis and Mixed Treatment Comparison of Randomized Trials of New Oral Anticoagulants in Atrial Fibrillation

Importance: Randomized studies have shown a decreased risk of intracranial hemorrhage (ICH) with use of novel oral anticoagulants (NOACs). However, it is unclear whether the magnitude of benefit is similar for all NOACs currently available.

Objective: To perform a systematic review and meta-analysis to quantitatively assess the rates of ICH within the framework of both conventional and Bayesian statistics.

Data Sources: The MEDLINE, CENTRAL, CINAHL, and EBSCO databases, supplemented with conference abstracts, were searched up to December 1, 2012, with no language restriction.

Study Selection: Randomized trials comparing NOACs vs a comparator and reporting on ICH events.

Data Extraction And Synthesis: The NOACs were pooled to perform a comparison with all comparators and among themselves in both traditional frequentist and Bayesian random-effects models using vague priors and Markov chain Monte Carlo simulation with Gibbs sampling, calculating pooled odds ratios and associated 95% confidence intervals as well as numbers needed to treat and 95% credible intervals for the Bayesian analysis.

Main Outcomes And Measures: Intracranial hemorrhage events associated with NOACs in comparison with comparators, expressed as odds ratios.

Results: Six studies (1 administering dabigatran etexilate mesylate, 2 administering rivaroxaban, and 3 administering apixaban) enrolling a total of 57,491 patients were included for analysis. The NOACs significantly reduced the risk of ICH against all comparators (odds ratio = 0.49; 95% CI, 0.36-0.65). Each of the 3 drugs reduced the risk of ICH, with Bayesian indirect comparison analysis not revealing a significant credible difference between the specific medications.

Conclusions And Relevance: Novel oral anticoagulants are uniformly associated with an overall reduced risk of ICH when used for stroke prevention in atrial fibrillation. Any of the currently available NOACs can be considered first line for patients at high risk for ICH.