Abstract
Background:
Direct oral anticoagulants (DOAC) have proven to be safe and effective alternatives to warfarin for stroke prevention in non-valvular atrial fibrillation (NVAF) as well as treatment of venous thromboembolism (VTE). Chronic kidney disease (CKD) is associated with increased risk of thromboembolism as well as bleeding. The objective of this research is to evaluate the efficacy and safety of DOAC compared to warfarin in patients with either VTE or NVAF across varying renal function.
Methods:
A systematic literature search using PubMed, Embase (1996 -November 2020), and Cochrane CENTRAL databases was conducted. Randomized controlled trials published in English between 1996 and November, 2020 evaluating the safety and efficacy of DOAC versus warfarin in patients with VTE or NVAF and CKD were included. Outcomes of interest were stroke or thromboembolic events, all-cause mortality, major bleeding (MB), and clinically relevant non-major bleeding (CRNMB). Random effects-model was used for meta-analysis. Risk of bias was assessed by utilizing the Revised Cochrane risk-of-bias tool for randomized trials.
Results:
After screening and review, a total of 9 randomized controlled trials with 96,103 participants were included. Of those, 81.5% (n=78,361) had a specific classification of renal function throughout the study. Majority of participants had mild to normal (48.5%) renal function, and 35% had mild impairment and moderate and severe renal impairment accounted for 16% and <1%, respectively. DOAC reduced risk of stroke or thromboembolic events compared to warfarin (RR 0.83, CI 95%: 0.77-0.89;
p
-value<0.01), as well as all-cause mortality (RR 0.91, CI 95%: 0.85-0.97;
p
-value<0.01). For safety outcomes, MB events were less likely to occur in DOAC group (RR 0.76, CI 95%: 0.69-0.84;
p
-value<0.01). Whereas, no significant difference was found between DOAC and warfarin in CRNMB events (RR 0.90, CI 95%: 0.73-1.12;
p-
value 0.36).
Conclusion:
DOAC demonstrated better efficacy in preventing stroke or thromboembolic events and in decreasing all-cause mortality. DOAC also caused less MB events compared to warfarin. No difference in CRNMB events was detected between these agents.