Effects of body mass index on the safety and effectiveness of direct oral anticoagulants: a retrospective review

Netley, Jared; Howard, K.; Wilson, W. Stephen

doi:10.1007/s11239-019-01857-2

Cited by 33 publications

(32 citation statements)

References 25 publications

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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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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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“…[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: 99%

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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“…The key findings of this study in Japanese patients with NVAF receiving rivaroxaban can be summarized as follows: first, baseline characteristics varied across BMI categories; second, the incidences of stroke/non-CNS SE/MI and all-cause mortality were significantly higher in those who were underweight than in those of normal weight; third, none of the BMI categories emerged as an independent predictor of major bleeding or stroke/ non-CNS SE/MI; fourth, in multivariable analyses, being underweight was found to be an independent predictor of all-cause mortality. Limited conclusions could be drawn from previous global studies investigating the impact of BMI on outcomes in patients with AF receiving anticoagulants because very few patients included in these analyses were underweight [7,[12][13][14]. The efficacy and safety of rivaroxaban in patients with NVAF were established in the global Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) and Japan-specific J-ROCKET AF phase 3 studies [15,16].…”

Section: Discussionmentioning

confidence: 99%

Impact of body mass index on real-world outcomes of rivaroxaban treatment in Japanese patients with non-valvular atrial fibrillation

et al. 2020

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This sub-analysis of the XAPASS, a prospective, single-arm, observational study, aimed to evaluate relationships between body mass index (BMI) and safety (major bleeding and all-cause mortality) and effectiveness [stroke/non-central nervous system (non-CNS) systemic embolism (SE)/myocardial infarction (MI)] outcomes in Japanese patients with non-valvular atrial fibrillation (NVAF) receiving rivaroxaban. Patients were categorized according to BMI (kg/m 2 ) as underweight (< 18.5), normal weight (18.5 to < 25), overweight (25 to < 30), or obese (≥ 30). In total, 9578 patients with NVAF completed the 1-year follow-up and were evaluated; of these, 7618 patients had baseline BMI data. Overall, 542 (5.7%), 4410 (46.0%), 2167 (22.6%), and 499 (5.2%) patients were underweight, normal weight, overweight, and obese, respectively. Multivariable Cox regression analysis demonstrated that none of the BMI categories were independent predictors of major bleeding whereas being underweight was independently associated with increased all-cause mortality [hazard ratio (HR) 3.56, 95% confidence interval (CI) 2.40-5.26, p < 0.001]. The incidence of stroke/non-CNS SE/MI was higher in patients who were underweight than in those of normal weight (HR 2.11, 95% CI 1.20-3.70, p = 0.009). However, in multivariable analyses, being underweight was not identified as an independent predictor of stroke/non-CNS SE/MI (HR 1.64, 95% CI 0.90-2.99, p = 0.104). In conclusion, the high incidence of thromboembolic events and all-cause mortality in patients who were underweight highlights that thorough evaluation of disease status and comorbidities may be required in this population.

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Effects of body mass index on the safety and effectiveness of direct oral anticoagulants: a retrospective review

Cited by 33 publications

References 25 publications

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

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

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

Impact of body mass index on real-world outcomes of rivaroxaban treatment in Japanese patients with non-valvular atrial fibrillation

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