AUTHOR=Kong Xiangyun , Zhu Yong , Pu Lianmei , Meng Shuai , Zhao Lihan , Zeng Wei , Sun Weiyan , Wu Guangming , Li Hong 

TITLE=Efficacy and Safety of Non-recommended Dose of New Oral Anticoagulants in Patients With Atrial Fibrillation: A Systematic Review and Meta-Analysis

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=Volume 8 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2021.774109

DOI=10.3389/fcvm.2021.774109

ISSN=2297-055X

ABSTRACT=Introduction: The real-world treatment of atrial fibrillation (AF) often involves the prescription of new oral anticoagulants (NOACs) using dose both lower and higher than recommended guidelines. Our study aimed to evaluate the efficacy and safety of non-recommended dose of NOACs in AF patients. 
Methods: A systematic search was performed for relevant studies across multiple electronic databases (PubMed, Embase, Cochrane Library, Clinical Trials Registry) from inception to May 1, 2021. Multicenter randomized trials and observational studies were selected with key reporting measures for inclusion involved efficacy outcomes including stroke or systemic thromboembolism along with safety endpoints assessing major or clinically relevant bleeding events. 
Results: A total of 11 eligible studies were included involving 48,648 patients receiving recommended dose of NOACs and 50,116 patients receiving non-recommended dose. Compared to AF patients treated with recommended dose regimens, administration of low dose of NOACs was associated with higher risk of stroke/systemic embolism (RR=1.24, 95%CI 1.14-1.35, P<0.00001), but without reducing bleeding risk (RR=1.18, 95%CI 0.91-1.53, P=0.21) and might cause higher risk of all-cause mortality (RR=1.58, 95%CI 1.25-1.99, P=0.0001). Moreover, high dose of NOACs did not show better efficacy (RR=1.71, 95%CI 1.06–2.76, P=0.03), although there was a trend that major or clinically relevant bleeding risk was increased (RR=1.57, 95%CI 0.96–2.58, P=0.07). 
Conclusions: AF patients treated with low dose of NOACs showed equivalent safety but with worse efficacy compared with recommended dose. High dose of NOACs was not superior to recommended dose regimens in preventing stroke/systemic embolism outcomes in AF patients.