Abstract
Objective We aimed to further investigate the efficacy and safety of low-dose NOACs by performing a meta-analysis of cohort studies. Background Meta-analyses of randomized controlled trials (RCTs) have demonstrated that low-dose non-vitamin K antagonist oral anticoagulants (NOACs) showed inferior efficacy compared with standard-dose NOACs, although they are still frequently prescribed for patients with atrial fibrillation (AF) in the clinical practice. Methods Cochrane Central Register of Controlled Trials (CENTRAL), Embase, and MEDLINE were systematically searched from the inception to September 9, 2021, for cohort studies that compared the efficacy and/or safety of low-dose NOACs in patients with AF. The primary outcomes were ischemic stroke and major bleeding, and the secondary outcomes were mortality, intracranial hemorrhage (ICH), and gastrointestinal hemorrhage (GH). Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated with the random-effect model. Results Twenty-five publications involving 487856 patients with AF were included. Compared with standard-dose NOACs, low-dose NOACs had comparable risks of ischemic stroke (HR = 1.03, 95% CI 0.96 to 1.11), major bleeding (HR = 1.12, 95% CI 0.97 to 1.28), ICH (HR = 1.09, 95% CI 0.88 to 1.36), and GH (HR = 1.11, 95% CI 0.92 to 1.33), except for a higher risk of mortality (HR = 1.41, 95% CI 1.21 to 1.65). Compared with warfarin, low-dose NOACs were associated with lower risks of ischemic stroke (HR = 0.72, 95% CI .67 to 0.78), mortality (HR = 0.67, 95% CI 0.59 to 0.77), major bleeding (HR = 0.64, 95% CI 0.53 to 0.79), ICH (HR = 0.57, 95% CI 0.42 to 0.77), and GH (HR = 0.78, 95% CI 0.64 to 0.95). Conclusions Low-dose NOACs were comparable to standard-dose NOACs considering risks of ischemic stroke, major bleeding, ICH, and GH, and they were superior to warfarin. Low-dose NOACs might be prescribed effectively and safely for patients with AF. Considering limitations, further well-designed prospective studies are foreseen.
Highlights
Atrial fibrillation (AF), known as a common cardiac arrhythmia worldwide, can cause ischemic stroke and seriously jeopardize the health of global elder patients [1]
We developed inclusion criteria for this meta-analysis prospectively. e criteria of studies screening were as follows: (1) the target population was patients with AF; (2) studies involved lose-dose non-vitamin K antagonist oral anticoagulants (NOACs) and standard-dose NOACs or warfarin; (3) studies included efficacy or safety outcomes; (4) the study type was the cohort
For patients with creatinine clearance rate (CrCl) of 30–50 mL/min, age ≥70 years, and a prior history of bleeding, standard-dose dabigatran was defined as 110 mg b.i.d. [14, 15]; for patients with CrCl of 15–50 mL/min, standard-dose rivaroxaban was defined as 10 mg q.d. [16, 17]; for patients with any two of the following characteristics, ≥ 80 years old, bodyweight
Summary
Atrial fibrillation (AF), known as a common cardiac arrhythmia worldwide, can cause ischemic stroke and seriously jeopardize the health of global elder patients [1]. Meta-analyses of RCTs assessed the efficacy and safety of standard-dose NOACs, low-dose NOACs, and warfarin in patients with AF. Low-dose NOACs were prescribed for 31%, 19%, and 29% of patients in Korea [7], France [8], and America [9], respectively. RCTs enroll a small, nonrepresentative subset of patients and overlook the important interactions between the patients and the real world, which can affect treatment outcomes [10]. Medication adherence, the key point for treatment effectiveness, is closely monitored in RCTs, which is not always the case in clinical practice [10]. Real-world cohort studies, which enroll patients of broad-spectrum baseline characteristics, may provide a comprehensive picture of the clinical practice. Erefore, we aimed to further investigate the efficacy and safety of low-dose NOACs by conducting a meta-analysis of all relevant cohort studies. Methods is meta-analysis was prepared according to the PRISMA (Preferred Reporting Items for Systemic Reviews and Metaanalysis) and MOOSE (Meta-Analysis of Observational Studies in Epidemiology) guidelines [11, 12]
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