Novel oral anticoagulants for the secondary prevention of cerebral ischemia: a network meta-analysis

Abstract

Background: Novel oral anticoagulants (NOACs) have shown to be both safe and effective for ischemic stroke prevention in patients with nonvalvular atrial fibrillation (NVAF). We conducted a network meta-analysis (NMA) using published data from secondary prevention subgroups of different phase III randomized clinical trials (RCTs) comparing individual NOACs with warfarin. Methods: Eligible studies were identified by searching MEDLINE and SCOPUS and the Cochrane Central Register of Controlled Trials databases. First, we conducted a pairwise meta-analysis for each pairwise comparison, and then we performed NMA to combine direct and indirect evidence for any given pair of treatments. The comparative effects of all NOACs against warfarin were ranked with the surface under the cumulative ranking (SUCRA) curve for each outcome. Results: We identified four RCTs (including 15,240 patients) comparing individual NOACs (apixaban, dabigatran, rivaroxaban) with warfarin. Using indirect evidence, dabigatran was related to a significantly lower risk of hemorrhagic stroke compared with rivaroxaban [risk ratio (RR) 0.28; 95% confidence interval (CI) 0.11-0.75], while rivaroxaban was associated with a significantly lower risk of major gastrointestinal bleeding compared with dabigatran (RR 0.14; 95% CI 0.03-0.74). We also performed clustered ranking plot for the primary efficacy and safety endpoints to identify the treatment with the probably best benefit-to-risk ratio profile. Conclusions:The three NOACs showed differences in terms of safety and efficacy for secondary stroke prevention in NVAF. Our findings can serve only as hypothesis generation and require independent confirmation in head-to-head RCTs, owing to the sparse available evidence and increased uncertainty in both indirect effect estimates and ranking of treatments.

Causes and Risk Factors of Cerebral Ischemic Events in Patients With Atrial Fibrillation Treated With Non–Vitamin K Antagonist Oral Anticoagulants for Stroke Prevention

“…Despite an adequate treatment with vitamin K antagonists, some patients with AF still suffer ischemic cerebrovascular events (1). Non-vitamin K antagonist oral anticoagulants (NOACs) are currently recommended as the preferred anticoagulant strategy for patients with non-valvular AF, given their more favorable risk benefit profiles over warfarin (2)(3)(4).…”

Clinical and Neuroimaging Characteristics in Embolic Stroke of Undetermined versus Cardioembolic Origin: A Population‐Based Study

“…We identified 21 ESUS (3.7% of the IS cohort) and 211 CE patients (37.1% of the IS cohort). Baseline characteristics and outcomes between ESUS patients and CE patients are presented in Table 1 [5][6][7][8][9][10][11][12][13][14][15][16][17]; P < .001), had higher prevalence of smoking (57.1 vs 15.6%, P < .001), had less often positive family history for cardiovascular disease (38.1 vs 73%, P < .001). Male sex was less common in ESUS (28.6 vs 59.2%; P = .007).…”

“…Nonvitamin K antagonists oral anticoagulants (NOACs) have proven to be at still comparable to warfarin in terms of efficacy for secondary prevention of stroke attributed to nonvalvular atrial fibrillation (AF), while their safety profile appears more favorable compared to vitamin K antagonists (VKA). 5,6 Since cardioembolism (due to AF or other causes) was speculated to be the primary underlying mechanism in ESUS, the efficacy of NOACs over low-dose aspirin for the secondary prevention of ESUS was recently tested in two large randomizedcontrolled clinical trials. 7,8 Both studies failed to show superiority of NOACs (dabigatran and rivaroxaban) over aspirin and challenged the hypothesis that occult AF may represent the main etiopathogenic mechanism of ESUS.…”

Efficacy and Safety of Non-Vitamin K Anticoagulants for Atrial Fibrillation in Relation to Different Renal Function Levels: A Network Meta-Analysis

“…Compared to the other NOACs, apixaban would offer the better endings for both efficacy (SUCRA 0.64) and safety (SUCRA 0.69). e article published by Katsanos et al also gave the similar conclusion that apixaban would offer an optimal benefit in comparison to the other NOACs in terms of the efficacy and safety, which identified the four RCTs [29]. One meta-regression analysis also gave the findings that apixaban would offer a better safety profile for preventing major bleeding, as well as the effect of prevention stroke or systemic embolism in patients with mild renal impairment [30].…”