Use of Direct Oral Anticoagulants in Morbidly Obese Patients

Kido, Kazuhiko; Lee, James C.; Hellwig, Thaddaus; Gulseth, Michael P.

doi:10.1002/phar.2353

Cited by 32 publications

(33 citation statements)

References 29 publications

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“…Rivaroxaban pharmacokinetic (PK) and pharmacodynamic (PD) studies indicate no significant impact of body weight on maximum concentration after the first dose (Cmax) or area under the curve (AUC) 46 . In contrast, apixaban Cmax, AUC, trough concentrations, half‐life and anti‐factor Xa activity were found to be reduced in obese patients compared to non‐obese, and dabigatran displayed reduced trough concentrations and Cmax 46‐48 . Edoxaban PK/PD data in obese patients are limited, but non‐renal clearance may increase with higher body weight 46,47 …”

Section: Resultsmentioning

confidence: 99%

“…48 Overall, retrospective cohorts of AF and VTE identified no significant differences between specific DOACs and warfarin for thromboembolism or major bleeding events. 48,49,51…”

Section: High Body Weightmentioning

confidence: 91%

“…46 In contrast, apixaban Cmax, AUC, trough concentrations, half-life and anti-factor Xa activity were found to be reduced in obese patients compared to non-obese, and dabigatran displayed reduced trough concentrations and Cmax. [46][47][48] Edoxaban PK/PD data in obese patients are limited, but non-renal clearance may increase with higher body weight. 46,47 Clinical outcomes associated with DOACs in obese patients remain to be elucidated in RCTs.…”

Section: High Body Weightmentioning

confidence: 99%

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A review of indications and comorbidities in which warfarin may be the preferred oral anticoagulant

et al. 2021

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What is known and objective: Direct oral anticoagulants (DOACs) are increasingly prescribed instead of warfarin for chronic anticoagulation for ease of dosing, fewer interactions, and less stringent monitoring. However, it is important to consider indications and comorbidities for which warfarin is still the preferred anticoagulant. This review aims to capture these clinical scenarios in which warfarin may still be preferred over DOACs. Methods: We undertook a comprehensive literature search using the PubMed database. Key search terms were based on DOAC clinical trial exclusion criteria, as well as indications and conditions in which the use of DOACs for anticoagulation has suggested harm. Society guidelines and tertiary literature were used to inform expert opinion where necessary. Studies were included if they investigated the use of DOACs or warfarin in the identified indications or conditions. Results and Discussion: Currently, evidence for the use of warfarin over DOACs for anticoagulation is strongest for patients with prosthetic valves, antiphospholipid syndrome, or a high risk of gastrointestinal bleeding. For several clinical situations, including mitral stenosis, obesity, altered gastrointestinal anatomy, pulmonary arterial hypertension, renal or hepatic impairment, and left ventricular thrombus, evidence is lacking but may eventually support the use of DOACs. Depending on indication and condition, appropriateness of DOAC use may vary by agent.What is new and conclusion: New evidence continues to support new indications and conditions in which DOACs may be appropriate to use for anticoagulation. There are key clinical scenarios, however, in which emerging literature continues to support warfarin as the preferred anticoagulant.

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Section: Resultsmentioning

confidence: 99%

“…48 Overall, retrospective cohorts of AF and VTE identified no significant differences between specific DOACs and warfarin for thromboembolism or major bleeding events. 48,49,51…”

Section: High Body Weightmentioning

confidence: 91%

Section: High Body Weightmentioning

confidence: 99%

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A review of indications and comorbidities in which warfarin may be the preferred oral anticoagulant

et al. 2021

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“…In addition, a subanalysis of RE-LY data in regard to patients’ characteristics revealed that due to reduced drug exposure, decreased peak concentrations, and shorter half-lives, patients with obesity showed 21% lower estimated dabigatran plasma concentrations than patients with normal weight [25, 43, 44]. Another single-center, retrospective cohort study described a higher thromboembolic event rate among obese patients on dabigatran than among those on apixaban or rivaroxaban, suggesting an avoidance of dabigatran in obese patients until further studies would be conducted [45, 46].…”

Section: Discussionmentioning

confidence: 99%

Stroke due to Left Atrial Appendage Thrombus after Pulmonary Vein Isolation despite Novel Oral Anticoagulant: A Case Report

et al. 2021

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In patients with atrial fibrillation, catheter ablation is suggested to reduce the mortality rate and is thus frequently performed. However, peri- and postprocedural thromboembolic complications as well as high recurrence rates of atrial fibrillation limit its advantages and require concomitant anticoagulation. With the advent of novel oral anticoagulants (NOACs), fixed dosing without routine laboratory monitoring became feasible. Nevertheless, several factors are associated with either an overdose or an insufficient drug activity of NOACs. We report on a patient with atrial fibrillation undergoing catheter ablation and cardioversion suffering from ischemic stroke despite being under oral anticoagulation. It turned out that the drug activity of the NOACs used was repeatedly insufficient in spite of regular intake and adequate dosing. In sum, drug activity controls should be taken into consideration in patients with thrombotic events despite oral anticoagulation with NOACs.

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“…Given that routine monitoring of DOAC concentrations is difficult to interpret and may be subject to variability, DOACs are not recommended in obese patients defined as a body mass index (BMI) ≥40 kg/m 2 and weight ≥120 kg 93 . In‐depth considerations in morbidly obese patients and the data since the Scientific and Standardization Committee (SSC)/ISTH recommendation have been reviewed previously in this Journal 94 . Since this publication, there have been two additional meta‐analyses assessing the rate of stroke or systemic embolism (SSE) and major bleeding in NVAF patients with obesity and morbid obesity 92 …”

Section: Transplant‐specific Considerations For Doac Usementioning

confidence: 99%

Use of direct‐acting oral anticoagulants in solid organ transplantation: A systematic review

et al. 2020

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The use of direct‐acting oral anticoagulants (DOACs) has increased secondary to the mounting evidence for comparable efficacy and potentially superior safety to vitamin K antagonists (VKAs) in the general population. However, insufficient data regarding DOAC use in solid organ transplant (SOT) recipients and numerous pharmacokinetic and pharmacodynamic considerations limit their use in this highly selected patient population. A systematic review of recent clinical evidence on the safety and efficacy of DOACs compared to VKAs in SOT recipients was conducted. Additional considerations including transplant‐specific strategies for DOAC reversal and common pharmacokinetic/pharmacodynamic concerns were also reviewed. Although current evidence is limited to single‐center retrospective analyses, DOACs, especially apixaban, appear to be a safe and effective alternative to VKAs for SOT recipients with stable graft function and without drug‐drug interactions. Reliable data on DOAC reversal at the time of transplant surgery are lacking, and clinicians should consider idarucizumab, andexanet alfa, and other non‐specific reversal agents on an individual patient basis. There is no evidence supporting deviations from the Food and Drug Administration labeling recommendations for DOAC dosing in the setting of drug‐drug interactions, obesity, and renal function, especially in patients on hemodialysis.

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Use of Direct Oral Anticoagulants in Morbidly Obese Patients

Cited by 32 publications

References 29 publications

A review of indications and comorbidities in which warfarin may be the preferred oral anticoagulant

A review of indications and comorbidities in which warfarin may be the preferred oral anticoagulant

Stroke due to Left Atrial Appendage Thrombus after Pulmonary Vein Isolation despite Novel Oral Anticoagulant: A Case Report

Use of direct‐acting oral anticoagulants in solid organ transplantation: A systematic review

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