AUTHOR=Shen Nan-Nan , Wu Yue , Wang Na , Kong Ling-Cong , Zhang Chi , Wang Jia-Liang , Gu Zhi-Chun , Chen Jin 

TITLE=Direct Oral Anticoagulants vs. Vitamin-K Antagonists in the Elderly With Atrial Fibrillation: A Systematic Review Comparing Benefits and Harms Between Observational Studies and Randomized Controlled Trials

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=Volume 7 - 2020

YEAR=2020

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2020.00132

DOI=10.3389/fcvm.2020.00132

ISSN=2297-055X

ABSTRACT=Background: Emerging publication of high-quality observational studies (OSs) fuel reassessment of treatment effect of direct oral anticoagulants (DOACs) in the elderly with atrial fibrillation (AF).

Methods: The MEDLINE, EMBASE, and Cochrane Library databases were systematically searched (through July 1, 2019) for eligible OSs and randomized controlled trials (RCTs) that reported effectiveness outcomes [stroke or systemic embolism (SE)] or safety outcomes [intracranial haemorrhage (ICH), major bleeding, gastrointestinal bleeding (GIB), myocardial infarction (MI), and all-cause mortality] for DOACs and vitamin-K antagonists (VKAs) in elderly AF patients. A random-effects model was applied to separately calculate adjusted hazard ratios (HRs) for OSs and relative risks (RRs) for RCTs, and interaction analyses and the ratio of HR (RHR) were used to assess the comparability between OSs and RCTs.

Results: A total of 32 studies involving 547,419 patients were included. No significant difference on treatment effect estimates was found between 27 OSs and 5 RCTs (Pinteraction>0.05 for each and all 95% confidence interval [CI] of RHR crossed 1.0). Compared with VKAs, DOACs significantly reduced risk for stroke/SE (OSs, HR: 0.87, 95% CI: 0.81-0.94; RCT, RR: 0.82, 95% CI: 0.67-0.96) and ICH (OSs: 0.47 [0.37-0.57]; RCTs: 0.47 [0.31-0.63]), without increasing risk for GIB (OSs: 1.21 [0.98-1.43]; RCTs: 1.34 [0.91-1.77]) and all-cause mortality (OSs: 1.01 [0.92-1.11]; RCTs: 0.94 [0.87-1.00]). Among OSs, DOACs significantly decreased risk for major bleeding (0.87 [0.77-0.98]) and MI (0.89 [0.79-0.99]). Dabigatran, but not other DOACs, significantly increased risk for GIB (1.48 [1.23-1.72]).

Conclusions: DOACs were demonstrated to be more effective and safer than VKAs in elderly AF patients. Whereas, dabigatran users had a 48% increase in risk for GIB.