Real-World Comparisons of Low-Dose NOACs versus Standard-Dose NOACs or Warfarin on Efficacy and Safety in Patients with AF: A Meta-Analysis

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.

Ischaemic stroke in a patient with non-valvular atrial fibrillation (NVAF) despite non-vitamin K oral anticoagulant (NOAC) therapy

“…Drug–drug interactions could theoretically reduce NOAC concentrations, particularly drugs that induce P-glycoprotein or CYP34A; subtherapeutic AC levels would predispose a patient to developing a recurrent ischaemic stroke. However, a systematic review by Li et al (2022) showed that the real-world risk of NOAC drug–drug interactions has been limited to a few case reports and retrospective observational analyses 37. Although avoiding enzyme inducers could hypothetically be recommended, there does not appear to be sufficient evidence to support this recommendation currently.…”