Evaluation of the efficacy of direct oral anticoagulants (DOACs) in comparison to warfarin in morbidly obese patients

Kalani, Charlene; Awudi, Elizabeth; Alexander, Thomas; Udeani, George; Surani, Salim

doi:10.1080/21548331.2019.1674586

Cited by 31 publications

(33 citation statements)

References 19 publications

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“…Another retrospective study examined patients with BMI >40 kg/m 2 or BW >120 kg receiving a DOAC (edoxaban excluded) or VKA for VTE, AF, or postoperative prophylaxis. 45 There was no significant difference in thrombotic or bleeding events between the DOAC and VKA groups. Within the DOACs, 36.4%, 18.2%, and 2.2% of patients receiving dabigatran, rivaroxaban, and apixaban, respectively, had thrombotic events.…”

Section: Studies With Multiple Doacs Includedmentioning

confidence: 80%

“…Within the DOACs, 36.4%, 18.2%, and 2.2% of patients receiving dabigatran, rivaroxaban, and apixaban, respectively, had thrombotic events. 45 The authors did not provide a statistical comparison between these groups. A third similar study was conducted at another institution in adults with a BMI ≥40 kg/m 2 receiving apixaban, rivaroxaban, or VKA for either AF or VTE.…”

Section: Studies With Multiple Doacs Includedmentioning

confidence: 99%

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Direct Oral Anticoagulants in Obesity: An Updated Literature Review

Sebaaly

Kelley

2020

Ann Pharmacother

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Objective: To review literature on the use of direct-acting oral anticoagulants (DOACs) in patients with high body weight (BW) and/or high body mass index (BMI) and to make recommendations regarding use in this patient population. Data Sources: A search using PubMed was conducted (inception to April 13, 2020) using the term DOAC AND the terms obesity OR body weight. A separate search was also conducted with individual DOACs (dabigatran, apixaban, rivaroxaban, edoxaban) and the aforementioned terms. Study Selection and Data Extraction: Studies included examined the effect of BW and/or BMI on DOAC pharmacokinetics, efficacy, or safety. Included studies had DOAC indications of prevention of stroke in nonvalvular atrial fibrillation, or treatment or long-term prevention of venous thromboembolism. Data Synthesis: The efficacy and safety of DOACs in patients with high BW/BMI has not yet been elucidated by randomized trials; however, 2016 international guidelines suggest avoiding their use in patients with a BW >120 kg or BMI >40 kg/m2. Since 2016, several studies have been published examining use of DOACs in this patient population. Relevance to Patient Care and Clinical Practice: This review thoroughly discusses the literature on DOACs in patients with a BW >120 kg or BMI >40 kg/m2 pre-2016 and post-2016 guidelines. Conclusions: Evidence indicates that each DOAC may have differences in outcomes when used in patients with a high BW/BMI. Currently, low-quality data are available that support avoiding dabigatran and considering apixaban or rivaroxaban; lack of sufficient data preclude a recommendation for edoxaban use in this patient population.

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Section: Studies With Multiple Doacs Includedmentioning

confidence: 80%

Section: Studies With Multiple Doacs Includedmentioning

confidence: 99%

Direct Oral Anticoagulants in Obesity: An Updated Literature Review

Sebaaly

Kelley

2020

Ann Pharmacother

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“…An additional number of smaller retrospective studies on patients with AF and/or VTE also evaluated the effect of NOAC in patients with BMI > 40 kg/m 2 or body weight > 120 kg and found similar efficacy and safety in comparison with warfarin. [72][73][74] Other studies found similar efficacy and safety of NOAC in obese patients compared with normal weight patients. [75][76][77] The majority of patients in the identified retrospective studies were treated with rivaroxaban or apixaban, whereas only four studies included a low proportion (10-30%) of patients on dabigatran, and none of the studies included patients on edoxaban.…”

Section: Non-vitamin K Antagonist Oral Anticoagulants Used For Treatmentmentioning

confidence: 88%

Dosage of Anticoagulants in Obesity: Recommendations Based on a Systematic Review

Abildgaard

Madsen

Hvas

2020

Semin Thromb Hemost

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Anticoagulants are frequently used as thromboprophylaxis and in patients with atrial fibrillation (AF) or venous thromboembolism (VTE). While obesity rates are reaching epidemic proportions worldwide, the optimal dosage for obese patients has not been established for most anticoagulants, including low-molecular-weight heparin (LMWH), non–vitamin K antagonist oral anticoagulants (NOAC), and pentasaccharides (fondaparinux). The aim of the present systematic review was to summarize the current knowledge and provide recommendations on dosage of LMWH, NOAC, and fondaparinux in obese patients (body mass index [BMI] ≥ 30 kg/m2 or body weight ≥ 100 kg). Based on a systematic search in PubMed and Embase, a total of 72 studies were identified. For thromboprophylaxis with LMWH in bariatric surgery (n = 20 studies), enoxaparin 40 mg twice daily, dalteparin 5,000 IE twice daily, or tinzaparin 75 IU/kg once daily should be considered for patients with BMI ≥ 40 kg/m2. For thromboprophylaxis with LMWH in nonbariatric surgery and in medical inpatients (n = 8 studies), enoxaparin 0.5 mg/kg once or twice daily or tinzaparin 75 IU/kg once daily may be considered in obese patients. For treatment with LMWH (n = 18 studies), a reduced weight-based dose of enoxaparin 0.8 mg/kg twice daily should be considered in patients with BMI ≥ 40 kg/m2, and no dose capping of dalteparin and tinzaparin should be applied for body weight < 140 kg. As regards NOAC, rivaroxaban, apixaban, or dabigatran may be used as thromboprophylaxis in patients with BMI < 40 kg/m2 (n = 4 studies), whereas rivaroxaban and apixaban may be administered to obese patients with VTE or AF, including BMI > 40 kg/m2, at standard fixed-dose (n = 20 studies). The limited available evidence on fondaparinux (n = 3 studies) indicated that the treatment dose should be increased to 10 mg once daily in patients weighing > 100 kg.

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“…with dose reduction to 30 mg according to baseline characteristics) for treating patients with either LBW or HBW, settings where there are few pharmacokinetic and pharmacodynamic data with NOACs. While a series of retrospective studies or posthoc analysis of trials evaluated the outcome of AF patients treated with oral anticoagulants and with various degrees of obesity, [20][21][22][23][24][25] or less frequently, with low body weight, 26 no study has previously assessed the pharmacokinetic and pharmacodynamic changes associated with the use of anticoagulants at extremes of body weight and correlated the data with clinical outcomes.…”

Section: Discussionmentioning

confidence: 99%

Edoxaban versus Warfarin in Patients with Atrial Fibrillation at the Extremes of Body Weight: An Analysis from the ENGAGE AF-TIMI 48 Trial

et al. 2020

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Background The effects of anticoagulants at extremes of body weight (BW) are not well described. The aim of this study was to analyze the pharmacokinetics/pharmacodynamics and clinical outcomes in patients randomized to warfarin, higher dose edoxaban (HDER), and lower dose edoxaban (LDER) regimens at extremes of BW in ENGAGE AF-TIMI 48. Methods and Results We analyzed three BW groups: low BW (LBW: <5th percentile, ≤55 kg, N = 1,082), middle BW (MBW: 45th–55th percentile, 79.8–84 kg, N = 2,153), and high BW (HBW: >95th percentile, ≥120 kg, N = 1,093). In the warfarin arm, LBW patients had higher rates of stroke/systemic embolism (SSE: 6.5 vs. 4.7 in MBW vs. 1.6% in HBW, P trend < 0.001), major bleeding (MB: 9.3 vs. 7.7 vs. 6.5%, P trend = 0.08), and worse net clinical outcome of systemic embolic event, MB, or death (31.5 vs. 19.1 vs. 16.0%, P trend < 0.0001). The time-in-therapeutic range with warfarin was lowest in LBW patients (63.0 vs. 69.3 vs. 70.1% patients, P trend < 0.001). The pharmacokinetic/pharmacodynamic profile of edoxaban was consistent across BW groups. The risk of SSE was similar between HDER and warfarin for each of the three weight groups (P int = 0.52, P int-trend = 0.86). MB was reduced by LDER versus warfarin (P int = 0.061, P int-trend = 0.023), especially in LBW patients. Net clinical outcomes were improved by HDER versus warfarin (P int = 0.087, P int-trend = 0.027), especially in LBW patients. Conclusion Patients with LBW in ENGAGE AF-TIMI 48 had in general a more fragile clinical status and poorer international normalized ratio control. The pharmacokinetic/pharmacodynamic profile of edoxaban was consistent across extremes of BW, resulting in similar efficacy compared with warfarin, while major or clinically relevant non-MB and net outcomes were most favorable with edoxaban as compared to warfarin in LBW patients.

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Evaluation of the efficacy of direct oral anticoagulants (DOACs) in comparison to warfarin in morbidly obese patients

Cited by 31 publications

References 19 publications

Direct Oral Anticoagulants in Obesity: An Updated Literature Review

Direct Oral Anticoagulants in Obesity: An Updated Literature Review

Dosage of Anticoagulants in Obesity: Recommendations Based on a Systematic Review

Edoxaban versus Warfarin in Patients with Atrial Fibrillation at the Extremes of Body Weight: An Analysis from the ENGAGE AF-TIMI 48 Trial

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