scholarly journals Safety and Efficacy of Direct Oral Anticoagulants in Morbidly Obese Patients: A Meta-Analysis

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1166-1166
Author(s):  
Talha Aijaz ◽  
Okechukwu Nwabueze Obi ◽  
Nida Khokhar ◽  
Prasanth Lingamaneni ◽  
Muhammad Zain Farooq
Keyword(s):  
Atrial Fibrillation ◽  
Major Bleeding ◽  
Observational Studies ◽  
Meta Analysis ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Morbidly Obese ◽  
Obese Patients ◽  
Efficacy And Safety ◽  
Randomized Control

Background: Direct oral anticoagulants (DOACS) were recently approved for anticoagulation in patients with atrial fibrillation for prevention of stroke and patient with venous thromboembolism (VTE) for the prevention of recurrent VTE. They have shown comparable efficacy and safety compared to vitamin K antagonist (VKA). DOACS have uniform pharmacokinetics and pharmacodynamics; hence, regular monitoring is not required. The morbidly obese patients may have increased volume of distribution and altered clearance which may alter the pharmacokinetics and consequently efficacy and safety of DOACS in these patients. 2016 International Society of Thrombosis and Hemostasis guideline recommends avoiding DOACS in a patient with body mass index (BMI) >40 kg/m2 or with body weight >120 kg due to lack of clinical trials. There is no sizeable randomized control trial to study the outcome of DOACS in morbidly obese patients, but subgroup analysis of a major randomized control trials and observational studies may provide the data on the efficacy and safety of DOACS. We intend to utilize this data in this meta-analysis to study the effectiveness and safety of DOACS in morbidly obese patients. Methods: Eligibility Criteria- Randomized control trial, observational studies including patients above 18 years with BMI>40kg/m2, body weight>120 kg and history of atrial fibrillation or VTE who are taking DOACS or warfarin for therapeutic purpose were included in the analysis. Study Selection- We searched Medline and Cochrane database. 52 studies were identified and 43 remained after removing duplicates. After assessing full text for eligibility 5 studies were included in the meta-analysis. Statistical analysis- Statistical analysis was performed with Review manager 5.3 by the Cochrane Collaboration. Forest plot was used to analyze publication bias. Heterogeneity in the studies were analyzed with Cochran Q analysis and I2 statistics. Results: Population characteristics were available in four studies. The mean age of the population ranged from 61.7 to 66.8 years, and mean BMI ranged from 44.8 to 46.7 kg/m2 . I2 analysis showed that the studies included were homogeneous, so fixed-effect model was applied. The incidence of recurrent VTE, stroke, or death ranged from 1.5% to 7.3% in DOACS compared to 1.2% to 7.9% in warfarin except in one study by Kalani et al. where it was 26% in DOACS vs. 20% in warfarin. Relative risk was 0.96 (confidence interval 0.75 - 1.28, p 0.78) indicating there was no significant difference in the primary efficacy outcome between the two groups. The incidence of major bleeding ranged from 1.5% to 4.8% in DOACS compared to 2.6% to 6.1% in warfarin. Relative risk was 0.72 (confidence interval 0.56 - 0.93, p 0.01) indicating that the risk of major bleeding was low among patient using DOACS. Conclusion: Efficacy of DOACS is similar compared to VKA when used for prevention of recurrence in VTE or prevention of stroke in atrial fibrillation in the patients with BMI>40 kg/m2 or bodyweight >120 kg. There was a trend towards a lower risk of bleeding in the patients with DOACS which is similar to the risk of major bleeding reported in non-obese patients in landmark randomized clinical trials. Only two studies included the patients with VTE, and additional studies are required to assess the safety and efficacy of DOACS among morbidly obese individuals with VTE. Figure Disclosures No relevant conflicts of interest to declare.

scholarly journals Efficacy and safety of direct oral anticoagulants in morbidly obese patients with non-valvular atrial fibrillation: a systematic review and meta-analysis

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
M Mhanna ◽  
A Beran ◽  
A Al-Abdouh ◽  
O Srour ◽  
W Abdulsattar ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Major Bleeding ◽  
Meta Analysis ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Morbidly Obese ◽  
Obese Patients ◽  
Efficacy And Safety ◽  
Systemic Embolism ◽  
Warfarin Group

Abstract Introduction Atrial fibrillation (AF) is the most common arrhythmia, with an estimated prevalence between 1–4%. On the other hand, obesity continued to be a prevalent health issue worldwide. Direct oral anticoagulants (DOACs) have been increasingly preferred over warfarin; however, The International Society of Thrombosis and Hemostasis (ISTH) recommended avoiding the use of DOACs in patients with a BMI >40 or weight >120 kg because of limited clinical data in these patients. In this meta-analysis, we aimed to evaluate the efficacy and safety of DOACs in morbidly obese patients with non-valvular AF. Method We performed a comprehensive literature search using multiple databases from database inception through January 2021, for all the studies that evaluated the efficacy and safety of DOACs in morbidly obese patients with non-valvular AF. The primary outcome of interest was stroke or systemic embolism (SSE) rate. The secondary outcome was major bleeding (MB). All meta-analyses were conducted using a random-effect model. Results A total of 10 studies including 89,494 morbidly obese patients (BMI >40 or weight >120 kg) with non-valvular AF on oral anticoagulation therapy (45427 on DOACs vs. 44067 on warfarin) were included in the final analysis. One included study was a randomized controlled trial (RCT), another study was a post hoc analysis of an RCT and the rest were retrospective cohort studies. The mean follow-up period was 1.8 years (range 8 months to 3.1 years). The SSE rate was significantly lower in DOACs group compared to warfarin group (odds ratio (OR): 0.71; 95% confidence interval (CI): 0.62, 0.81; p<0.0001; I2=0%). MB rate was also significantly lower in DOACs group compared to the warfarin group (OR 0.60, 95% CI 0.46–0.78, P<0.0001, I2=86%). Subgroup analysis in the rivaroxaban and apixaban AF cohort showed a statistically significant difference in SSE and MB event rates favoring both over warfarin therapy. Dabigatran showed non-inferiority to warfarin in SSE rate but superiority in the safety outcome. Conclusions Our meta-analysis demonstrated that DOACs are effective and safe when compared to warfarin in morbidly obese patients. However, more large scale randomized clinical trials are needed to further evaluate the efficacy and safety of DOACs compared to warfarin in this cohort of patients. FUNDunding Acknowledgement Type of funding sources: None. Stroke and systemic embolism events Major bleeding events

scholarly journals Direct oral anticoagulants versus vitamin K antagonists in patients with atrial fibrillation and cancer a meta-analysis

2020 ◽  
Author(s):  
Marco Valerio Mariani ◽  
Michele Magnocavallo ◽  
Martina Straito ◽  
Agostino Piro ◽  
Paolo Severino ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Vitamin K ◽  
Major Bleeding ◽  
Meta Analysis ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Significant Risk ◽  
Bleeding Complications ◽  
Efficacy And Safety

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.

scholarly journals Efficacy and Safety of Direct Oral Anticoagulants in Patients with Diabetes and Nonvalvular Atrial Fibrillation: Meta-Analysis of Observational Studies

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Bo Cao ◽  
Xingcan Yao ◽  
Lifang Zhang ◽  
Xiaobo Hu ◽  
Min Chen ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Atrial Fibrillation ◽  
Ischemic Stroke ◽  
Observational Studies ◽  
Meta Analysis ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Efficacy And Safety ◽  
Nonvalvular Atrial Fibrillation ◽  
Patients With Diabetes

Background. This meta-analysis was performed to compare the efficacy and safety of direct oral anticoagulants (DOACs) with vitamin K antagonists (VKAs) for stroke prevention in real-world patients with diabetes and nonvalvular atrial fibrillation (NVAF) through observational studies. Methods. PubMed, Embase, and Web of Science databases were searched up to August 2020 for eligible studies. Outputs were presented as risk ratios (RRs) and corresponding 95% confidence intervals (CIs) by using a random-effect model. Results. Seven observational studies involving 249,794 diabetic NVAF patients were selected. Compared with VKAs, the use of DOACs was associated with significantly reduced risks of stroke ( RR = 0.56 , 95% CI 0.45-0.70; p < 0.00001 ), ischemic stroke ( RR = 0.61 , 95% CI 0.48-0.78; p < 0.0001 ), stroke or systemic embolism (SSE) ( RR = 0.81 , 95% CI 0.68-0.95; p = 0.01 ), myocardial infarction ( RR = 0.69 , 95% CI 0.55-0.88; p = 0.002 ), major bleeding ( RR = 0.75 , 95% CI 0.63-0.90; p = 0.002 ), intracranial hemorrhage ( RR = 0.50 , 95% CI 0.44-0.56; p < 0.00001 ), and major gastrointestinal bleeding ( RR = 0.77 , 95% CI 0.62-0.95; p = 0.02 ), and a borderline significant decrease in major adverse cardiac events ( RR = 0.87 , 95% CI 0.75-1.00; p = 0.05 ) in NVAF patients with diabetes. Conclusion. For patients with NVAF and diabetes in real-world clinical settings, DOACs showed superior efficacy and safety profile over VKAs and significantly reduced risks of stroke, ischemic stroke, SSE, myocardial infarction, major bleeding, intracranial hemorrhage, and major gastrointestinal bleeding.

Abstract 14569: Direct Oral Anticoagulants in the Treatment of Acute Venous Thromboembolism in Obese Patients: A Systematic Review With Meta-analysis

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Vicky Mai ◽  
Emmanuelle Marceau-Ferron ◽  
Laurent BERTOLETTI ◽  
Yves Lacasse ◽  
Sebastien Bonnet ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Data Extraction ◽  
Meta Analysis ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Random Effect ◽  
Random Effect Model ◽  
Morbidly Obese ◽  
Obese Patients ◽  
Efficacy And Safety

Background: Obesity is a real burden and its prevalence is constantly increasing. High body weight is a risk factor for developing venous thromboembolism (VTE). Direct oral anticoagulants’ (DOAC) pharmacokinetics and pharmacodynamics are affected by obesity. Their efficacy and safety in obese (BMI ≥30kg/m 2 ) and morbidly obese (BMI ≥40kg/m 2 ) patients are still unclear in the treatment of VTE. Objectives: To compare the efficacy and safety of DOAC with vitamin K antagonist (VKA)/low molecular weight heparin (LMWH) in the acute treatment of VTE in obese and morbidly obese patients. The primary efficacy outcome was VTE recurrences. The safety outcomes were major bleeding (MB) and clinically relevant non-MB (CRNMB). All-cause mortality was also assessed. Hypothesis: We hypothesized that DOAC would present the same efficacy and safety for the treatment of acute VTE in obese and morbidly obese patients compared to VKA/LMWH. Methods: A systematic literature search (MEDLINE, EMBASE, CENTRAL, Web of Science) was conducted from inception to April 15 th 2020, identifying trials studying DOAC in the treatment of acute VTE in obese patients. Studies were included if one of the outcomes was reported. Two independent reviewers performed the study selection, data extraction, risk of bias assessment and strength of body evidence evaluation using the GRADE methodology. Analyses were conducted using the Mantel-Haenszel method based on a random-effect model. Relative risks (RR) were estimated for the effect measure with 95% confidence intervals. Results: From 1240 citations screened, we included 21 studies (58,590 patients). VTE recurrences was similar with DOAC compared to VKA/LMWH in obese patients (risk ratio (RR): 1.03; 95%CI 0.93-1.15; p=0.55) and morbidly obese patients (RR 1.06; 95CI 0.94-1.19; p=0.35). DOAC was associated with a reduction in MB in obese patients (RR 0.57; 95%CI 0.34-0.94; p=0.03) and morbidly obese patients (RR 0.71; 95%CI 0.50-1.00; p=0.05) compared to VKA/LMWH. In obese patients, no difference was observed in CRNMB with DOAC compared to VKA/LMWH. Conclusion: DOAC is as effective in reducing VTE and is associated with less MB compared to VKA/LMWH in obese and morbidly obese patients.

Gender Differences in Efficacy and Safety of Direct Oral Anticoagulants in Atrial Fibrillation: Systematic Review and Network Meta-analysis

2018 ◽  
Vol 52 (11) ◽  
pp. 1135-1142 ◽  
Author(s):  
Bruria Hirsh Raccah ◽  
Amichai Perlman ◽  
Donna R. Zwas ◽  
Sarit Hochberg-Klein ◽  
Reem Masarwa ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Gender Differences ◽  
Major Bleeding ◽  
Randomized Clinical Trials ◽  
Data Extraction ◽  
Meta Analysis ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Baseline Risk ◽  
Efficacy And Safety

Background: Studies indicate that women with atrial fibrillation (AF) are less likely to receive anticoagulants despite their higher risk of stroke compared with men. Objective: To evaluate whether the efficacy and safety of direct oral anticoagulants (DOACs) differ in women with AF as compared with men. Our secondary aim was to examine gender differences regarding the safety and efficacy of specific DOACs. Data Sources: MEDLINE, EMBASE, Cochrane, and ClinicalTrials.gov were searched through March 2017. Study Selection and Data Extraction: Randomized clinical trials that reported on major bleeding and stroke with DOACs in women and men with AF were included. Meta-analysis and network meta-analysis was performed. Data Synthesis: Five trials met the inclusion criteria. Among 66 389 patients, 37.8% were women. Women treated with DOACs were at higher risk of stroke and systemic embolism compared with men (RR = 1.19; 95% CI = 1.04-1.35; I2 = 10%) but there was a significantly lower risk of major bleeding in women compared with men (RR = 0.86; 95% CI = 0.78-0.94; I2 = 0%). Network meta-analyses suggested differences between various DOACs in men and women. Limitations: Patient-level data enabling control for differences in baseline risk and head-to-head comparisons between DOACs were not available. Relevance to Patient Care and Clinical Practice: Undertreatment with DOACs among women cannot be justified. Conclusion: Women treated with DOACs had a lower rate of major bleeding and higher rate of stroke and systemic emboli compared with men. Further investigation of DOACs, including differences between the DOACs in specific populations is warranted.

Comparing the Efficacy and Safety of Direct Oral Anticoagulants With Warfarin in the Morbidly Obese Population With Atrial Fibrillation

2018 ◽  
Vol 53 (2) ◽  
pp. 165-170 ◽  
Author(s):  
Kazuhiko Kido ◽  
Surachat Ngorsuraches
Keyword(s):  
Atrial Fibrillation ◽  
Ischemic Stroke ◽  
Rate Ratio ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Morbidly Obese ◽  
Obese Patients ◽  
Efficacy And Safety ◽  
Warfarin Group ◽  
Group Rate

Background: The International Society of Thrombosis and Haemostasis recommends avoiding direct oral anticoagulants (DOACs) in morbidly obese patients with a body mass index (BMI) >40 kg/m2 or weight >120 kg because of limited clinical data in this group of patients. Objectives: The objective of this study was to evaluate the efficacy and safety of DOACs in morbidly obese patients with atrial fibrillation or flutter. Methods: A retrospective, single-center cohort study was conducted of patients older than 18 years, with BMI >40 kg/m2 or weight >120 kg, who were diagnosed as having atrial fibrillation or flutter and who received warfarin or DOACs (ie, dabigatran, rivaroxaban, or apixaban). The primary efficacy outcome was the incidence of ischemic stroke or transient ischemic attack (TIA), whereas the primary safety outcome was the incidence of major bleeding. Results: A total of 64 patients in each group were included in the study analysis. The incidence rate of ischemic stroke or TIA was 1.75%/year in the DOAC group compared with 2.07%/year in the warfarin group (rate ratio = 0.84; 95% CI = 0.23 to 3.14; P = 0.80). The incidence rate of major bleeding was 2.18%/year in the DOAC group, compared with 4.97%/year in the warfarin group (rate ratio = 0.44; 95% CI = 0.15 to 1.25; P = 0.11). Conclusion and Relevance: Apixaban and rivaroxaban may be considered as alternatives to warfarin for atrial fibrillation or flutter in morbidly obese patients. Dabigatran use in morbidly obese patients needs caution until further studies are conducted.

scholarly journals Comparison of the Direct Oral Anticoagulants and Warfarin in Patients With Atrial Fibrillation and Valvular Heart Disease: Updated Systematic Review and Meta-Analysis of Randomized Controlled Trials

2021 ◽  
Vol 8 ◽  
Author(s):  
Yasmin de Souza Lima Bitar ◽  
Andre Rodrigues Duraes ◽  
Leonardo Roever ◽  
Mansueto Gomes Neto ◽  
Liliane Lins-Kusterer ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Systematic Review ◽  
Heart Disease ◽  
Major Bleeding ◽  
Valvular Heart Disease ◽  
Meta Analysis ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Risk Of Bias ◽  
Efficacy And Safety

Background: Direct oral anticoagulants (DOACS) are approved for use in non-valvular atrial fibrillation (AF). This systematic review and meta-analysis aimed to evaluate the efficacy and safety of DOACs vs. warfarin and update the evidence for treatment of AF and valvular heart disease (VHD).Methods: We identified randomized clinical trials (RCTs) and post-hoc analyses comparing the use of DOACS and Warfarin in AF and VHD, including biological and mechanical heart valves (MHV), updating from 2010 to 2020. Through systematic review and meta-analysis, by using the “Rev Man” program 5.3, the primary effectiveness endpoints were stroke and systemic embolism (SE). The primary safety outcome was major bleeding, while the secondary outcome included intracranial hemorrhage. We performed prespecified subgroup analyses. Data were analyzed by risk ratio (RR) and 95% confidence interval (CI) and the I-square (I2) statistic as a quantitative measure of inconsistency. Risk of bias and methodological quality assessment of included trials was evaluated with the modified Cochrane risk-of-bias tool.Results: We screened 326 articles and included 8 RCTs (n = 14.902). DOACs significantly reduced the risk of stroke/SE (RR 0.80, 95% CI: 0.68–0.94; P = 0.008; moderate quality evidence; I2 = 2%) and intracranial hemorrhage (RR 0.40, 95% CI: 0.24–0.66; P = 0.0004; I2 = 49%) with a similar risk of major bleeding (RR 0.83, 95% CI: 0.56–1.24; P = 0.36; I2 = 88%) compared to Warfarin.Conclusions: In this update, DOACs remained with similar efficacy and safety compared to warfarin in thromboprophylaxis for AF and VHD.

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.

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