Non-vitamin K antagonist oral anticoagulants (NOACs) versus vitamin K antagonists (VKAs) in (morbidly) obese or low body weight patients with atrial fibrillation: a meta-analysis

EP Europace ◽  
2021 ◽  
Vol 23 (Supplement_3) ◽  
Author(s):  
M Grymonprez ◽  
TL De Backer ◽  
S Steurbaut ◽  
K Boussery ◽  
L Lahousse
Keyword(s):  
Body Weight ◽  
Cohort Studies ◽  
Vitamin K ◽  
Meta Analysis ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Phase Iii ◽  
Morbidly Obese ◽  
Class Iii ◽  
Observational Cohort

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Fund for Scientific Research Flanders (FWO) Background Oral anticoagulants are crucial for preventing systemic thromboembolism in atrial fibrillation (AF), with guidelines preferring non-vitamin K antagonist oral anticoagulants (NOACs) over vitamin K antagonists (VKAs) in the general AF population. However, as NOACs are administered in fixed doses, concerns of unintentional underdosing in morbidly obese patients and unintentional overdosing in underweight patients have emerged. Moreover, VKAs are still recommended in morbidly obese patients (body mass index (BMI) ≥40 kg/m², body weight >120 kg) due to lack of data for NOACs in these patients. Purpose A critical appraisal of the benefit-risk profile of NOACs in AF patients across the body weight spectrum.  Methods After searching the Medline database, phase III randomized controlled trials (RCTs) and longitudinal observational cohort studies on the effectiveness and safety of NOACs versus VKAs in obese (BMI ≥30 kg/m²), and class III obese (BMI ≥40 kg/m²) non-valvular AF patients, and in low body weight (≤60 kg) AF patients during a mean/median follow-up of ≥6 months were included. The meta-analyses were performed using a random effects model with the Mantel-Haenszel method. Results A meta-analysis based on 4 phase III RCTS and 3 longitudinal observational cohort studies demonstrated that NOAC use in obese and class III obese AF patients was associated with significantly lower stroke/systemic embolism (stroke/SE) risks (RR 0.82, 95%CI [0.71-0.96]; and RR 0.75, 95%CI [0.64-0.87], respectively), similar to lower major bleeding risks (RR 0.83, 95%CI [0.69-1.00]; and RR 0.74, 95%CI [0.57-0.95], respectively), and similar mortality risks (RR 0.92, 95%CI [0.73-1.15]; and RR 1.17, 95%CI [0.83-1.64], respectively) as compared to VKAs. In AF patients ≤60 kg, significantly lower stroke/SE (RR 0.63, 95%CI [0.56-0.71]) and major bleeding risks (RR 0.71, 95%CI [0.62-0.80]), and similar mortality risks (RR 0.68, 95%CI [0.42-1.10]) were observed for NOAC- versus VKA-treated patients in a meta-analysis based on 4 phase III RCTs and 2 longitudinal observational cohort studies. Conclusions The benefit-risk profile of NOACs seems preserved in (morbidly) obese AF patients and patients with low body weight of ≤60 kg. However, more data are needed in underweight AF patients (BMI <18.5 kg/m²) and on differences between NOACs to further optimize management in these patient subgroups.

scholarly journals The Risk of Gastrointestinal Bleeding between Non-Vitamin K Antagonist Oral Anticoagulants and Vitamin K Antagonists in the Asian Atrial Fibrillation Patients: A Meta-Analysis

2020 ◽  
Vol 18 (1) ◽  
pp. 137
Author(s):  
Kuang-Tsu Yang ◽  
Wei-Chih Sun ◽  
Tzung-Jiun Tsai ◽  
Feng-Woei Tsay ◽  
Wen-Chi Chen ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Gastrointestinal Bleeding ◽  
Vitamin K ◽  
Meta Analysis ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Vitamin K Antagonist ◽  
Cochrane Library ◽  
Secondary Outcome ◽  
Optimal Dosage

Background: Non-vitamin K antagonist oral anticoagulants (NOACs) are more commonly used to prevent atrial fibrillation (AF) patients from thromboembolic events than vitamin K antagonists (VKAs). However, the gastrointestinal bleeding (GIB) risk in the Asian AF patients associated with NOACs in comparison with VKAs remained unaddressed. Materials and Methods: A systematic search of studies on NOACs and VKAs in the Asian AF patients was conducted in PubMed, Cochrane Library, and ClinicalTrials.gov. The primary outcome was the hazard ratio (HR) of any GIB associated with NOACs versus VKAs. The secondary outcome was the GIB risks in different kinds of NOACs compared with VKAs. Results: This meta-analysis included two randomized controlled trials (RCTs) and four retrospective studies, comprising at least 200,000 patients in total. A significantly lower HR of GIB risks was found in all kinds of NOACs than VKAs in the Asian AF patients (HR: 0.633; 95% confidence interval: 0.535–0.748; p < 0.001). Additionally, the GIB risks of different NOACs were apixaban (HR: 0.392), edoxaban (HR: 0.603), dabigatran (HR: 0.685), and rivaroxaban (HR: 0.794), respectively. Conclusions: NOACs significantly reduced the risk of GIB in the Asian AF patients compared with VKAs. In the four NOACs compared with VKAs, apixaban probably had a trend of the least GIB risk. We need further head-to-head studies of different NOACs to confirm which NOAC is the most suitable for Asian AF patients and to know the optimal dosage regimen of different NOACs.

Meta-analysis comparing impact of age, sex and renal function on the efficacy and safety of new oral anticoagulants vs. vitamin K antagonists for the treatment of acute venous thromboembolisms

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
J She ◽  
B.Z Zhuo
Keyword(s):  
Renal Function ◽  
Venous Thromboembolism ◽  
Creatinine Clearance ◽  
Vitamin K ◽  
Meta Analysis ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Funding Source ◽  
Efficacy And Safety ◽  
Acute Venous Thromboembolism

Abstract Background New direct oral anticoagulants (NOACs), as a preferable treatment option for acute venous thromboembolism (VTE) have been recommended with practical advantages as compared to Vitamin K antagonists (VKAs) in clinical practice. Purpose In our study, we performed a meta-analysis to determine the efficacy and safety of NOACs vs. VKAs in patients with different age, sex and renal function for the treatment of VTE. Methods Electronic databases (accessed October 2019) were systematically searched to identify RCTs evaluating apixaban, dabigatran, edoxaban, and rivaroxaban versus VKAs for the treatment of acute venous thromboembolism. Results NOACs was associated with a borderline higher efficacy in female (OR 0.79, 95% CI 0.62–1.02), and a significantly higher efficacy in patients with age more than 75 (OR 0.51, 95% CI 0.32–0.80) and creatinine clearance less than 50 mL/min (OR 0.57, 95% CI 0.32–0.99). NOACs also show advantage in terms of major or clinically relevant non-major bleeding in male (OR 0.72, 95% CI 0.60–0.86), and patients with creatinine clearance more than 50 mL/min (OR 0.75, 95% CI 0.67–0.84). Conclusions NOACs have exhibited clinical preference among patients with acute VTE as compared to VKA with significantly decreased thrombosis events and lower bleeding complications, especially in patients with age more than 75 and creatinine clearance less than 50 mL/min. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): This study was supported by the National Natural Science Foundation of China (81800390) and the Natural Science Foundation of Shaanxi province (2018KW067).

Management of pulmonary embolism in patients with cancer

ESC CardioMed ◽  
2018 ◽  
pp. 2790-2794
Author(s):  
Cihan Ay ◽  
Florian Posch
Keyword(s):  
Pulmonary Embolism ◽  
Vitamin K ◽  
Meta Analysis ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Standard Of Care ◽  
Current Standard ◽  
Patients With Cancer ◽  
High Index Of Suspicion ◽  
Excessive Anticoagulation

Pulmonary embolism (PE) is a frequent complication in patients with cancer. Clinicians have to maintain a high index of suspicion to reduce the large proportion of PEs that remain undiagnosed in the cancer population. Thrombolysis is not a standard treatment for haemodynamically unstable patients with cancer-associated PE because the risk of haemorrhage can be excessive. Anticoagulation with a low-molecular-weight heparin (LMWH) for at least 6 months is the current standard of care for the treatment of cancer-associated PE, while vitamin K antagonists are a reasonable second choice for patients with contraindications against LMWH or a strong preference towards an oral agent. Although an indirect network meta-analysis suggests that non-vitamin K-dependent oral anticoagulants may be comparably efficacious and safe as LMWH for treating PE in cancer patients, these agents cannot be recommended as a standard first-line treatment at this time because a head-to-head comparison to the standard of care has not yet been reported. Anticoagulation beyond 6 months is an emerging concept; however, the patient population that may benefit from this intervention still needs to be defined. Guidance statements facilitate the management of challenging patients with brain metastases, unsuspected PE, thrombocytopenia, and recurrent PE.

The NOACs: clinical pharmacology

ESC CardioMed ◽  
2018 ◽  
pp. 268-272
Author(s):  
Jeffrey Weitz
Keyword(s):  
Atrial Fibrillation ◽  
Vitamin K ◽  
Active Site ◽  
Randomized Clinical Trials ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Factor Xa ◽  
Vitamin K Antagonist ◽  
Phase Iii ◽  
High Affinity

The limitations of vitamin K antagonists prompted the development of new oral anticoagulants that could be administered in fixed doses without routine coagulation monitoring. Focusing on thrombin and factor Xa because of their prominent roles in coagulation, structure-based design led to the development of small molecules that bind to the active site pockets of these enzymes with high affinity and specificity. Four non-vitamin K antagonist oral anticoagulants are now licensed: dabigatran, which inhibits thrombin, and rivaroxaban, apixaban, and edoxaban, which inhibit factor Xa. In phase III randomized clinical trials that included over 100,000 patients these agents have proven to be at least as effective as vitamin K antagonists for prevention of stroke in patients with non-valvular atrial fibrillation and for treatment of venous thromboembolism, and to produce less bleeding, particularly less intracranial bleeding.

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.

RE-COVERY DVT/PE: Rationale and design of a prospective observational study of acute venous thromboembolism with a focus on dabigatran etexilate

2017 ◽  
Vol 117 (02) ◽  
pp. 415-421 ◽  
Author(s):  
Walter Ageno ◽  
Ivan B. Casella ◽  
Chee Kok Han ◽  
Gary E. Raskob ◽  
Sebastian Schellong ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Vitamin K ◽  
Large Scale ◽  
Vitamin K Antagonists ◽  
Phase 1 ◽  
Dabigatran Etexilate ◽  
Oral Anticoagulants ◽  
Phase Iii ◽  
Real World Data ◽  
Phase Iii Studies

SummaryThe therapeutic management of venous thromboembolism (VTE) is rapidly evolving. Following the positive results of pivotal large-scale randomised trials, the non-vitamin K antagonist oral anticoagulants (NOACs) represent an important alternative to standard anticoagulation. In phase III studies, dabigatran was as effective as, and significantly safer than warfarin. Additional information on real-world data of dabigatran is now warranted. RE-COVERY DVT/PE is a multi-centre, international, observational (i. e. non-interventional) study enrolling patients with acute DVT and/or PE within 30 days after objective diagnosis. The study is designed with two phases. Phase 1 has a cross-sectional design, enrolling approximately 6000 patients independently of treatment choice, with the aim of providing a contemporary picture of the management of VTE worldwide. Phase 2 has a prospective cohort design, with follow-up of one year, enrolling 8000 patients treated with dabigatran or vitamin K antagonists (VKAs) with the aim of comparing their safety, defined by the occurrence of major bleeding, and effectiveness, defined by the occurrence of symptomatic recurrent VTE. RE-COVERY DVT/PE will complement both the results of other observational studies in this field and the results of phase III studies with dabigatran, in particular by assessing its clinical benefit in various patient subgroups treated in routine clinical practice.

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