Efficacy and safety of edoxaban in comparison with dabigatran, rivaroxaban and apixaban for stroke prevention in atrial fibrillation

2014 ◽  
Vol 111 (05) ◽  
pp. 981-988 ◽  
Author(s):  
Torben Larsen ◽  
Lars Rasmussen ◽  
Gregory Y. H. Lip ◽  
Flemming Skjøth
Keyword(s):  
Atrial Fibrillation ◽  
Gastrointestinal Bleeding ◽  
Ischaemic Stroke ◽  
Major Bleeding ◽  
Stroke Prevention ◽  
Dabigatran Etexilate ◽  
Indirect Comparison ◽  
High Dose ◽  
Efficacy And Safety ◽  
Comparison Analysis

SummaryLarge Phase 3 clinical trials for stroke prevention in atrial fibrillation (AF) have compared non-vitamin K antagonist oral anticoagulants (NOACs) against warfarin, with the edoxaban trial only recently reported. In the absence of head to head trials directly comparing these NOACs against each other, we compared the efficacy and safety of edoxaban to other agents by an indirect comparison analysis. We performed an indirect comparison analysis of edoxaban (2 dose strategies) against apixaban (1 dose), dabigatran etexilate (2 doses) and rivaroxaban (1 dose), for their relative efficacy and safety against each other. For high-dose edoxaban vs apixaban, there were no significant differences in efficacy endpoints, mortality, myocardial infarction and major bleeding. Apixaban was associated with less major or clinically relevant non-major bleeding (hazard ratio [HR] 0.79; 95% confidence interval [CI] 0.70–0.90) and gastrointestinal bleeding (HR 0.72; 95% CI 0.53–0.99). For dabigatran 110 mg twice daily, there were no significant differences in the main efficacy or safety endpoints. Dabigatran 150 mg bid was associated with lower stroke/systemic embolism (SE) (HR 0.75; 95% CI 0.56–0.99), stroke (HR 0.73; 95% CI 0.55–0.96) and haemorrhagic stroke (HR 0.48; 95% CI 0.23–0.99). There were no significant differences between high-dose edoxaban vs rivaroxaban for efficacy endpoints or mortality, but rivaroxaban had more major and/or clinically relevant non-major bleeding. When compared to low-dose edoxaban, apixaban was associated with lower stroke/SE (HR 0.70; 95% CI 0.55–0.89), stroke (HR 0.70; 95% CI 0.55–0.92) and ischaemic stroke (HR 0.65; 95% CI 0.50–0.89), but more major bleeding (HR 1.47; 95% CI 1.20–1.80). For dabigatran 110 mg bid, there were no significant differences in the efficacy endpoints, but dabigatran 110 mg bid had higher major (and gastrointestinal) bleeding. Dabigatran 150 mg bid and rivaroxaban were associated with lower stroke/SE and ischaemic stroke, but higher bleeding rates. In the present analysis, we have provided for the first time, comparisons of efficacy and safety of edoxaban against other NOACs. Notwithstanding the significant limitations of an indirect comparison analysis, some differential effects are evident with the NOACs for stroke prevention, allowing us to allow the prescriber a ‘choice’ to be able to fit the drug to the patient clinical profile (and vice versa).Note: The review process for this paper was fully handled by Christian Weber, Editor in Chief.

A single centre experience of the efficacy and safety of dabigatran etexilate used for stroke prevention in atrial fibrillation

2013 ◽  
Vol 38 (1) ◽  
pp. 39-44 ◽  
Author(s):  
Lok Bin Yap ◽  
Beni Isman Rusani ◽  
Dhanan Umadevan ◽  
Zulkeflee Muhammad ◽  
Azlan Hussin ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Stroke Prevention ◽  
Dabigatran Etexilate ◽  
Efficacy And Safety ◽  
Single Centre ◽  
Single Centre Experience

scholarly journals Efficacy and Safety of Non-Vitamin K Antagonist Oral Anticoagulants in Patients with Atrial Fibrillation and Cancer: Meta-Analysis of Observational Studies

2021 ◽  
Author(s):  
Bo Cao ◽  
Xiaobo Hu ◽  
Min Chen ◽  
Mingfeng Shen ◽  
Lan Xu
Keyword(s):  
Gastrointestinal Bleeding ◽  
Ischaemic Stroke ◽  
Vitamin K ◽  
Major Bleeding ◽  
Observational Studies ◽  
Meta Analysis ◽  
Oral Anticoagulants ◽  
Vitamin K Antagonist ◽  
Efficacy And Safety ◽  
Systemic Embolism

Abstract BackgroundEvidence on the safety and effectiveness of non-vitamin K antagonist oral anticoagulants (NOACs) in atrial fibrillation (AF) patients with cancer is rather limited, so we performed this meta-analysis to compare the efficacy and safety of NOACs with vitamin K antagonists (VKAs) in real-world patients with AF and cancer. MethodsThe PubMed and Embase databases were searched up to June 2020 for eligible studies. Outputs were presented as risk ratios (RRs) and corresponding 95% confidence intervals (CIs) using a random-effects model. ResultsA total of five observational studies involving 232,234 cancer patients with AF were included. Compared with VKAs, use of NOACs was associated with decreased risks of stroke or systemic embolism (RR, 0.79; 95% CI 0.69-0.90), ischaemic stroke (RR, 0.82; 95% CI, 0.72-0.93), venous thromboembolism (VTE) (RR, 0.28; 95% CI 0.14-0.53), all-cause death (RR, 0.57; 95% CI 0.50-0.64), major bleeding (RR, 0.60; 95% CI 0.51-0.72) and intracranial or gastrointestinal bleeding (RR, 0.61; 95% CI, 0.51-0.73). In subgroup analysis, all NOACs showed similar rates of stroke or systemic embolism, ischaemic stroke but reduced rates of all-cause death, major bleeding and intracranial or gastrointestinal bleeding compared to VKAs. ConclusionsIn this combined analysis of real-world observational studies, NOACs showed lower risks of stroke or systemic embolism, ischaemic stroke, VTE, all-cause death and reduced rates of major bleeding and intracranial or gastrointestinal bleeding compared to VKAs in patients with AF and cancer.

scholarly journals Non-vitamin K oral anticoagulants for secondary stroke prevention in patients with atrial fibrillation

2020 ◽  
Vol 22 (Supplement_I) ◽  
pp. I13-I21
Author(s):  
Hans-Christoph Diener ◽  
Graeme J Hankey ◽  
J Donald Easton ◽  
Gregory Y H Lip ◽  
Robert G Hart ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Ischaemic Stroke ◽  
Vitamin K ◽  
Major Bleeding ◽  
Stroke Prevention ◽  
Oral Anticoagulants ◽  
Haemorrhagic Stroke ◽  
Recurrent Bleeding ◽  
Secondary Stroke Prevention ◽  
Significant Difference

Abstract The aims of this article are to review the evidence regarding the use of non-vitamin K oral anticoagulants (NOACs) for secondary stroke prevention as compared to vitamin K antagonists in patients with atrial fibrillation (AF) and in patients with embolic strokes of uncertain source (ESUS), and when to initiate or resume anticoagulation after an ischaemic stroke or intracranial haemorrhage. Four large trials compared NOACs with warfarin in patients with AF. In our meta-analyses, the rate of all stroke or systemic embolism (SE) was 4.94% with NOACs vs. 5.73% with warfarin. Among the patients with AF and previous transient ischaemic attack or ischaemic stroke, the rate of haemorrhagic stroke was halved with a NOAC vs. warfarin, and the rate of major bleeding was 5.7% with a NOAC vs. 6.4% with warfarin. There was no significant difference in mortality. In a trial comparing apixaban with aspirin in patients with AF, the rate of stroke or SE was 2.4% at 1 year with apixaban vs. 9.2% at 1 year with aspirin and the rates of major bleeding were 4.1% with apixaban vs. 2.9% with aspirin. Data from registries confirmed the results from the randomized trials. Initiation or resumption of anticoagulation after ischaemic stroke or cerebral haemorrhage depends on the size and severity of stroke and the risk of recurrent bleeding. Two large trials tested the hypothesis that NOACs are more effective than 100 mg aspirin in patients with ESUS. Neither trial showed a significant benefit of the NOAC over aspirin. In the meta-analysis, the rate all stroke or SE was 4.94% with NOACs vs. 5.73% with warfarin and the rate of haemorrhagic stroke was halved with a NOAC. The four NOACs had broadly similar efficacy for the major outcomes in secondary stroke prevention.

Abstract 14825: Efficacy and Safety of Dabigatran, Rivaroxaban, and Apixaban Compared to Warfarin in Asian Patients With Non-valvular Atrial Fibrillation: A Systemic Review and Meta-analysis

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Weijia Li ◽  
Damianos Kokkinidis ◽  
Yu Chiang Wang
Keyword(s):  
Atrial Fibrillation ◽  
Ischemic Stroke ◽  
Major Bleeding ◽  
Stroke Prevention ◽  
Meta Analysis ◽  
Random Effect Model ◽  
Systemic Review ◽  
Efficacy And Safety ◽  
Asian Patients ◽  
All Cause Mortality

Background: Most of the randomized clinical trials that led to the wide use of non-vitamin K antagonist oral anticoagulants (NOACs) for stroke prevention in patients with atrial fibrillation (AF) originated from western countries. We aimed to systematically review and quantitatively synthesize the real-world data regarding the efficacy and safety of dabigatran, rivaroxaban, and apixaban compared to warfarin for stroke prevention in Asian patients with non-valvular AF. Methods: Medline and Cochrane databases were reviewed. A random-effect model meta-analysis was used and I-square was utilized to assess the heterogeneity. The primary outcome was ischemic stroke. The secondary outcomes were all-cause mortality, major bleeding, intracranial hemorrhage, and gastrointestinal bleeding. Results: Twelve studies from East Asia or Southeast Asia and 429496 patients in total were included. Dabigatran, rivaroxaban, and apixaban were associated with a significant reduction in the incidence of ischemic stroke (HR=0.78, 95% CI, 0.65-0.94; HR=0.79, 95% CI, 0.74-0.85, HR=0.70, 95% CI, 0.62-0.78; respectively), all-cause mortality (HR=0.68, 95% CI, 0.56-0.83; HR=0.66, 95% CI, 0.52-0.84; HR=0.66, 95% CI, 0.49-0.90; respectively), and major bleeding (HR=0.61, 95%CI, 0.54-0.69; HR=0.70, 95% CI, 0.54-0.90; HR=0.58, 95% CI, 0.43-0.78; respectively) compared to warfarin. Conclusion: Dabigatran, rivaroxaban, and apixaban appear to be superior to warfarin in both efficacy and safety in Asian patients with non-valvular AF.

scholarly journals A Systematic Review of the Efficacy and Safety of Direct Oral Anticoagulants in Atrial Fibrillation Patients with Diabetes Using a Risk Index

2021 ◽  
Vol 10 (13) ◽  
pp. 2924
Author(s):  
Domenico Acanfora ◽  
Marco Matteo Ciccone ◽  
Valentina Carlomagno ◽  
Pietro Scicchitano ◽  
Chiara Acanfora ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Atrial Fibrillation ◽  
Major Bleeding ◽  
Oral Anticoagulants ◽  
Risk Index ◽  
Direct Oral Anticoagulants ◽  
Anticoagulation Therapy ◽  
Efficacy Rate ◽  
Cochrane Central Register ◽  
Efficacy And Safety

Diabetes mellitus (DM) represents an independent risk factor for chronic AF and is associated with unfavorable outcomes. We aimed to evaluate the efficacy and safety of direct oral anticoagulants (DOACs) in patients with atrial fibrillation (AF), with and without diabetes mellitus (DM), using a new risk index (RI) defined as: RI =Rate of EventsRate of Patients at Risk. In particular, an RI lower than 1 suggests a favorable treatment effect. We searched MEDLINE, MEDLINE In-Process, EMBASE, PubMed, and the Cochrane Central Register of Controlled Trials. The risk index (RI) was calculated in terms of efficacy (rate of stroke/systemic embolism (stroke SEE)/rate of patients with and without DM; rate of cardiovascular death/rate of patients with and without DM) and safety (rate of major bleeding/rate of patients with and without DM) outcomes. AF patients with DM (n = 22,057) and 49,596 without DM were considered from pivotal trials. DM doubles the risk index for stroke/SEE, major bleeding (MB), and cardiovascular (CV) death. The RI for stroke/SEE, MB, and CV death was comparable in patients treated with warfarin or DOACs. The lowest RI was in DM patients treated with Rivaroxaban (stroke/SEE, RI = 0.08; CV death, RI = 0.13). The RIs for bleeding were higher in DM patients treated with Dabigatran (RI110 = 0.32; RI150 = 0.40). Our study is the first to use RI to homogenize the efficacy and safety data reported in the DOACs pivotal studies against warfarin in patients with and without DM. Anticoagulation therapy is effective and safe in DM patients. DOACs appear to have a better efficacy and safety profile than warfarin. The use of DOACs is a reasonable alternative to vitamin-K antagonists in AF patients with DM. The RI can be a reasonable tool to help clinicians choose between DOACs or warfarin in the peculiar set of AF patients with DM.

Abstract 200: Cost-Effectiveness of Newer Anticoagulants for Stroke Prevention in Atrial Fibrillation

2013 ◽  
Vol 6 (suppl_1) ◽  
Author(s):  
Brendan L Limone ◽  
William L Baker ◽  
Craig I Coleman
Keyword(s):  
Atrial Fibrillation ◽  
Cost Effectiveness ◽  
Stroke Prevention ◽  
Indirect Comparison ◽  
Cost Effective ◽  
The United States ◽  
Base Case ◽  
Treatment Comparison ◽  
Newer Anticoagulants ◽  
The Cost

Background: A number of new anticoagulants for stroke prevention in atrial fibrillation (SPAF) have gained regulatory approval or are in late-stage development. We sought to conduct a systematic review of economic models of dabigatran, rivaroxaban and apixaban for SPAF. Methods: We searched the Medline, Embase, National Health Service Economic Evaluation Database and Health Technology Assessment database along with the Tuft’s Registry through October 10, 2012. Included models assessed the cost-effectiveness of dabigatran (150mg, 110mg, sequential), rivaroxaban or apixaban for SPAF using a Markov model or discrete event simulation and were published in English. Results: Eighteen models were identified. All models utilized a lone randomized trial (or an indirect comparison utilizing a single study for any given direct comparison), and these trials were clinically and methodologically heterogeneous. Dabigatran 150mg was assessed in 9 of models, dabigatran 110mg in 8, sequential dabigatran in 9, rivaroxaban in 4 and apixaban in 4. Adjusted-dose warfarin (either trial-like, real-world prescribing or genotype-dosed) was a potential first-line therapy in 94% of models. Models were conducted from the perspective of the United States (44%), European countries (39%) and Canada (17%). In base-case analyses, patients typically were at moderate-risk of ischemic stroke, initiated anticoagulation between 65 and 73 years of age, and were followed for or near a lifetime. All models reported cost/quality-adjusted life-year (QALY) gained, and while 22% of models reported using a societal perspective, no model included costs of lost productivity. Four models reported an incremental cost-effectiveness ratio (ICER) for a newer anticoagulant (dabigatran 110mg (n=4)/150mg (n=2); rivaroxaban (n=1)) vs. warfarin above commonly reported willingness-to-pay thresholds. ICERs (in 2012US$) vs. warfarin ranged from $3,547-$86,000 for dabigatran 150mg, $20,713-$150,000 for dabigatran 110mg, $4,084-$21,466 for sequentially-dosed dabigatran and $23,065-$57,470 for rivaroxaban. In addition, apixaban was demonstrated to be an economically dominant strategy compared to aspirin and to be dominant or cost-effective ($11,400-$25,059) vs. warfarin. Based on separate indirect treatment comparison meta-analyses, 3 models compared the cost-effectiveness of these new agents and reported conflicting results. Conclusions: Cost-effectiveness models of newer anticoagulants for SPAF have been extensively published. Models have frequently found newer anticoagulants to be cost-effective, but due to the lack of head-to-head trial comparisons and heterogeneity in clinical characteristic of underlying trials and modeling methods, it is currently unclear which of these newer agents is most cost-effective.

Stroke prevention in atrial fibrillation

ESC CardioMed ◽  
2018 ◽  
pp. 2185-2195
Author(s):  
Michael D. Ezekowitz ◽  
Amanulla N. Khaji
Keyword(s):  
Atrial Fibrillation ◽  
Gastrointestinal Bleeding ◽  
Stroke Prevention ◽  
Left Atrial ◽  
Haemorrhagic Stroke ◽  
Atrial Appendage ◽  
Ageing Population ◽  
The Novel ◽  
Left Atrial Appendage Occlusion ◽  
Novel Agent

Atrial fibrillation (AF) is a modern epidemic affecting the rapidly growing ageing population. Stroke related to AF can be devastating. The use of anticoagulation and more recently left atrial appendage occlusion devices makes stroke related to AF a potentially preventable event. Warfarin reduces stroke in completed trials against placebo by about 80%. Warfarin and apixaban, the only novel agent to be tested against aspirin, beats aspirin by about 50% and dual antiplatelet therapy by a similar margin. The novel agents dabigatran, rivaroxaban, apixaban, and edoxaban reduce strokes by 9–30% compared to warfarin. Approximately 80% of dabigatran is excreted by the kidneys (RE-LY trial), and dabigatran reduced the risk of stroke or systemic embolism compared to warfarin by 34% (p <0.001, superiority) for a 150 mg dose, and by 9% (p <0.001, non-inferiority) for a 110 mg dose. The risk of haemorrhagic stroke, compared to warfarin, was significantly lower with a 150 mg dose (74%) as well as with a 110 mg dose (69%). Gastrointestinal bleeding occurred more frequently in subjects who received 150 mg twice daily (1.51%/year) compared to 110 mg twice daily (1.12%/year) and warfarin (1.02%/year). Dyspepsia occurs in 5–10% of patents leading to permanent discontinuation in 2%.

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