Reappraisal of Non-vitamin K Antagonist Oral Anticoagulants in Atrial Fibrillation Patients: A Systematic Review and Meta-Analysis

Abstract

Background: Recent observational studies have compared effectiveness and safety profiles between non-vitamin K antagonist oral anticoagulants (NOACs) and warfarin in patients with atrial fibrillation (AF). Nevertheless, the confounders may exist due to the nature of clinical practice-based data, thus potentially influencing the reliability of results. This systematic review and meta-analysis were conducted to compare the effect of NOACs with warfarin based on the propensity score-based observational studies vs. randomized clinical trials (RCTs).Methods: Articles included were systematically searched from the PubMed and EMBASE databases until March 2021 to obtain relevant studies. The primary outcomes were stroke or systemic embolism (SSE) and major bleeding. Hazard ratios (HRs) and 95% confidence intervals (CIs) of the outcomes were extracted and then pooled by the random-effects model.Results: A total of 20 propensity score-based observational studies and 4 RCTs were included. Compared with warfarin, dabigatran (HR, 0.82 [95% CI, 0.71–0.96]), rivaroxaban (HR, 0.80 [95% CI, 0.75–0.85]), apixaban (HR, 0.75 [95% CI, 0.65–0.86]), and edoxaban (HR, 0.71 [95% CI, 0.60–0.83]) were associated with a reduced risk of stroke or systemic embolism, whereas dabigatran (HR, 0.76 [95% CI, 0.65–0.87]), apixaban (HR, 0.61 [95% CI, 0.56–0.67]), and edoxaban (HR, 0.58 [95% CI, 0.45–0.74]) but not rivaroxaban (HR, 0.92 [95% CI, 0.84–1.00]) were significantly associated with a decreased risk of major bleeding based on the observational studies. Furthermore, the risk of major bleeding with dabigatran 150 mg was significantly lower in observational studies than that in the RE-LY trial, whereas the pooled results of observational studies were similar to the data from the corresponding RCTs in other comparisons.Conclusion: Data from propensity score-based observational studies and NOAC trials consistently suggest that the use of four individual NOACs is non-inferior to warfarin for stroke prevention in AF patients.

Long-term comparative effectiveness and safety of dabigatran, rivaroxaban, apixaban and edoxaban in patients with atrial fibrillation: A nationwide cohort study

“…Our results are in line with findings from randomized ( Connolly et al, 2009 ; Granger et al, 2011 ; Patel et al, 2011 ; Giugliano et al, 2013 ; Ruff et al, 2014 ; Carnicelli et al, 2022 ) and observational studies ( Hernandez et al, 2017 ; Rutherford et al, 2020 ; Van Ganse et al, 2020 ; Graham et al, 2019 ; Halvorsen et al, 2017 ; Halvorsen et al, 2021 ; Yao et al, 2016 ; Chan et al, 2018 ; Hohnloser et al, 2018 ; Larsen et al, 2016 ; Liu et al, 2021 ; Ujeyl et al, 2018 ; Vinogradova et al, 2018 ; Wong et al, 2020 ; Bai et al, 2017a ; Ntaios et al, 2017 ; van den Ham et al, 2021 ), and corroborate guideline recommendations ( Steffel et al, 2021 ) to prefer NOACs over VKAs in the general AF population. This is reassuring, as we have investigated unselected AF patients on a full-population scale during long-term follow-up.…”

“…In line with results from RCTs ( Connolly et al, 2009 ; Granger et al, 2011 ; Patel et al, 2011 ; Giugliano et al, 2013 ; Ruff et al, 2014 ; Carnicelli et al, 2022 ) and observational studies ( Hernandez et al, 2017 ; Van Ganse et al, 2020 ; Graham et al, 2019 ; Halvorsen et al, 2021 ; Yao et al, 2016 ; Hohnloser et al, 2018 ; Larsen et al, 2016 ; Liu et al, 2021 ; Ujeyl et al, 2018 ; Vinogradova et al, 2018 ; Wong et al, 2020 ; Bai et al, 2017a ; Ntaios et al, 2017 ; van den Ham et al, 2021 ; Bai et al, 2017b ; Forslund et al, 2018 ), the risk of intracranial bleeding, the most feared and frequently fatal complication of anticoagulation, was significantly lower with NOACs compared to VKAs ( Ruff et al, 2014 ). No differences between individual NOACs on the risk of intracranial bleeding were observed, except for a significantly lower risk with apixaban compared to rivaroxaban, which has been noted before ( Cohen et al, 2018 ; Rutherford et al, 2020 ; Zhang et al, 2021 ; Zhu et al, 2021 ).…”

Vitamin D, vitamin D supplementation and atrial fibrillation risk in the general population: updated systematic review and meta-analysis of prospective studies

“…The quality of observational studies and randomized controlled trials (RCTs) was assessed using the Newcastle-Ottawa Quality Assessment Scale (NOS) and Cochrane Bias Risk Assessment Tool, respectively (13)(14)(15). The NOS evaluates bias across three domains (selection, comparability, and outcomes) using eight items, with a maximum total score of nine.…”

Stroke in Patients with Atrial Fibrillation: Epidemiology, Screening, and Prognosis

“…Intermittent undersensing of continuous AF and inadequate sensing of very brief episodes of AF or other ATAs are frequently observed and may lead to inappropriate AHRE detection [ 90 , 91 , 92 ]. An erroneous AHRE detection may be triggered by oversensing of the far field R-wave [ 93 ] or sensing of retrograde atrial depolarizations [ 92 , 94 , 95 ]. In the Atrial Fibrillation Reduction Atrial Pacing (ASSERT) trial, 17.3% of the AHREs were inaccurately detected, which was primarily attributed to repetitive non-reentrant ventriculo-atrial synchronous rhythm [ 94 ].…”