Effectiveness of Direct Oral Anticoagulants in Obese Adults With Atrial Fibrillation: An Overview of Systematic Reviews and Meta-analysis

2021 ◽  
Vol 30 ◽  
pp. S157
Author(s):  
F. Shaikh ◽  
R. Wynne ◽  
R. Castelino ◽  
S. Inglis ◽  
C. Ferguson
2021 ◽  
Vol 8 ◽  
Author(s):  
Fahad Shaikh ◽  
Rochelle Wynne ◽  
Ronald L. Castelino ◽  
Sally C. Inglis ◽  
Caleb Ferguson

Background: Atrial Fibrillation (AF) is the most common sustained cardiac arrhythmia. Obesity is an independent risk factor for AF. Anticoagulants have been strongly recommended by all international guidelines to prevent stroke. However, altered pathophysiology in obese adults may influence anticoagulant pharmacology. Direct oral anticoagulants (DOACs) in the context of obesity and AF have been examined in recent systematic reviews. Despite the similarities in included studies, their results and conclusions do not agree.Methods and Results: The protocol for this review was registered with PROSPERO (CRD42020181510). Seven key electronic databases were searched using search terms such as “atrial fibrillation,” “obese,*” “overweight,” “novel oral anticoagulant,” “direct oral anticoagulant,” “DOAC,” “NOAC,” “apixaban,” dabigatran,” “rivaroxaban,” and “edoxaban” to locate published and unpublished studies. Only systematic reviews with meta-analyses that examined the effect of DOACs in overweight or obese adults with AF, published in the English language, were included. A total of 9,547 articles were initially retrieved. After removing the duplicates, title and abstract review and full-text review, five articles were included in the systematic review. From these only RCTs were included in the meta-analyses. There was disagreement within the published systematic reviews on DOACs in obesity. The results from our meta-analysis did not show any significant difference between all body mass index (BMI) groups for all outcomes at both 12 months and for the entire trial duration. Non-significant differences were seen among the different types of DOACs.Conclusion: There was no difference between the BMI classes in any of the outcomes assessed. This may be due to the limited number of people in the trial that were in the obese class, especially obese class III. There is a need for large prospective trials to confirm which DOACs are safe and efficacious in the obese class III adults and at which dose.


2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
F Shaikh ◽  
R Wynne ◽  
R L Castelino ◽  
S C Inglis ◽  
C Ferguson

Abstract Background Obesity may influence the pharmacology of direct oral anticoagulants (DOAC) that are recommended by all international guidelines for stroke prevention in adults with atrial fibrillation (AF). Purpose To evaluate the safety and efficacy of DOACs in obese adults with AF. Methods Medline, CINAHL, Scopus, Web of Science, Cochrane Database, Johanna Briggs Institute, Embase, Psych Info and ProQuest were searched till April 2020. Only systematic reviews with meta-analyses, that were published after 2005 and were in the English language were included. Articles were screened by title and abstract, followed by full text assessment using the Covidence systematic review software. Data was extracted using a standardised extraction tool. AMSTAR-2® and ROBIS® tools were used for quality and risk of bias assessment. The entire process was undertaken by two investigators at each stage of the study selection, appraisal, and data extraction. Disagreements were resolved through consensus discussion with a third arbitrary investigator. Statistical analyses were performed using the DerSimonian and Laird method for random effects. Meta-analysis was performed using only randomised controlled trials from eligible systematic reviews at both 12 months and across the entire trial. Primary outcomes assessed was stroke (ischemic or haemorrhagic) or systemic or pulmonary embolism. Secondary outcomes assessed included all-cause mortality, transient ischemic attack, myocardial infarction, major bleed, all cause-hospitalisation, and cardiovascular mortality. Results Of the 8162 articles screened, a total of five systematic reviews were included in this overview. There was disagreement within the published reviews on the effect of DOAC in obesity. Four of the five reviews were of either “low” or “critically low” quality, with inconsistencies in data extraction and appropriateness of the included studies and statistical methods used in analysis. Data from only the RE-LY, AVERROES and ENGAGE AF-TIMI 48 trials, were available for the meta-analysis, which did not find any significant difference between all BMI groups for all outcomes, at both time points. However, analysis of the different weight groups versus normal weight, highlighted non-significant differences between the different DOACs. Conclusion There was no difference between the BMI classes in any of the outcomes assessed. However, the non-significant trends that were seen, suggests individual superiority of DOACs may exist within the obese adult populations. There is a need for prospective trials to evaluate which DOACs are safe and efficacious in the obese class III adults and at which dose. FUNDunding Acknowledgement Type of funding sources: Other. Main funding source(s): Australian Government Research Training Program (RTP) Heart Foundation of AustraliaNational Health and Medical Research Council (NHMRC)


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Ali Hage ◽  
Daniel Dolan ◽  
Viviane G Nasr ◽  
Luis Castelo-Branco ◽  
Daniel Motta-Calderon ◽  
...  

Introduction: The evidence for use of direct oral anticoagulants (DOACs) in the management of post-operative cardiac surgery atrial fibrillation (POAF) is limited and mostly founded on clinical trials that excluded this patient population. Hypothesis: We performed a systematic review and meta-analysis of clinical trials and observational studies to evaluate the hypothesis that DOACs are safe compared to warfarin for the anticoagulation of patients with POAF. Methods: We searched PubMed, EMBASE, Web of Science, clinicaltrials.gov, and the Cochrane Library for clinical trials and observational studies comparing DOAC with warfarin in patients ≥18 years old who had post-cardiac surgery atrial fibrillation. Primary outcomes included stroke, systemic embolization, bleeding, and mortality, with secondary outcome of hospital readmission. We performed a random-effects meta-analysis. Results: We found 3 clinical trials, 1 prospective and 12 retrospective cohort studies eligible for inclusion with a total of 10,538 patients (3,207 DOAC patients and 7,331 warfarin patients). The meta-analysis for the primary outcomes showed significantly lower risk of stroke with DOAC use (6 studies, 7143 patients, RR 0.64; 95% CI 0.50 to 0.81, I2: 0.0%) compared to warfarin, a trend towards lower risk of systemic embolization (4 studies, 7289 patients, RR 0.64, 95% CI 0.41 to 1.01, I2: 31.99%) and similar risks of bleeding (14 studies, 10182 patients, RR 0.91; 95% CI 0.74 to 1.10, I2: 26.6%) and mortality (12 studies, 9843 patients, relative risk [RR] 1.01; 95% CI 0.74 to 1.37, I2: 26.5%) The secondary outcome of hospital readmission had similar risk between groups. Conclusions: Current evidence suggests that DOACs, compared to warfarin, in the management of atrial fibrillation after cardiac surgery is associated with lower risk of stroke and a strong trend for lower risk of systemic embolization, and no evidence of increased risk for hospital readmission, bleeding or mortality.


Author(s):  
Marco Valerio Mariani ◽  
Michele Magnocavallo ◽  
Martina Straito ◽  
Agostino Piro ◽  
Paolo Severino ◽  
...  

Abstract Background Direct oral anticoagulants (DOACs) are recommended as first-line anticoagulants in patients with atrial fibrillation (AF). However, in patients with cancer and AF the efficacy and safety of DOACs are not well established. Objective We performed a meta-analysis comparing available data regarding the efficacy and safety of DOACs vs vitamin K antagonists (VKAs) in cancer patients with non-valvular AF. Methods An online search of Pubmed and EMBASE libraries (from inception to May, 1 2020) was performed, in addition to manual screening. Nine studies were considered eligible for the meta-analysis involving 46,424 DOACs users and 182,797 VKA users. Results The use of DOACs was associated with reduced risks of systemic embolism or any stroke (RR 0.65; 95% CI 0.52–0.81; p 0.001), ischemic stroke (RR 0.84; 95% CI 0.74–0.95; p 0.007) and hemorrhagic stroke (RR 0.61; 95% CI 0.52–0.71; p 0.00001) as compared to VKA group. DOAC use was associated with significantly reduced risks of major bleeding (RR 0.68; 95% CI 0.50–0.92; p 0.01) and intracranial or gastrointestinal bleeding (RR 0.64; 95% CI 0.47–0.88; p 0.006). Compared to VKA, DOACs provided a non-statistically significant risk reduction of the outcomes major bleeding or non-major clinically relevant bleeding (RR 0.94; 95% CI 0.78–1.13; p 0.50) and any bleeding (RR 0.91; 95% CI 0.78–1.06; p 0.24). Conclusions In comparison to VKA, DOACs were associated with a significant reduction of the rates of thromboembolic events and major bleeding complications in patients with AF and cancer. Further studies are needed to confirm our results.


2020 ◽  
Vol 4 (7) ◽  
pp. 1034-1040 ◽  
Author(s):  
Francesco Violi ◽  
Annarita Vestri ◽  
Danilo Menichelli ◽  
Arianna Di Rocco ◽  
Daniele Pastori ◽  
...  

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