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.
Author(s): Chatterjee S(1), Sardar P(2), Biondi-Zoccai G(3), Kumbhani DJ(4).
Affiliation(s): Author information:
(1)Division of Cardiology, Brown University, Providence, Rhode Island.
(2)Department of Medicine, New York Medical College-Metropolitan Hospital Center,
New York.
(3)Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University
of Rome, Latina, Italy.
(4)Division of Cardiology, University of Texas Southwestern Medical Center, Dallas.
Publication date & source: 2013, JAMA Neurol. , 70(12):1486-90
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.
|