Direct-acting oral anticoagulant use at extremes of body weight: Literature review and recommendations

2020 ◽  
Vol 77 (11) ◽  
pp. 865-876
Author(s):  
Kelly Covert ◽  
Donald L Branam
Keyword(s):  
Body Weight ◽  
Oral Anticoagulants ◽  
Careful Consideration ◽  
Cardioembolic Stroke ◽  
Safety And Efficacy ◽  
High Body Weight ◽  
High Body ◽  
Published Evidence ◽  
Agent Selection ◽  
Direct Acting

Abstract Purpose To review the literature on treatment of venous thromboembolism (VTE) and prevention of cardioembolic stroke with direct-acting oral anticoagulants (DOACs) in low- and high-body-weight patients and to make recommendations regarding agent selection and dosing in these patient populations. Summary The selection and optimal dosing of DOACs in low- and high-body-weight patients has not yet been fully elucidated by clinical trials; however, evidence suggests that issues of both safety and efficacy in patients at the extremes of body weight may warrant careful consideration when selecting a DOAC for such patients. This review provides a thorough discussion of the use of DOACs in the treatment of VTE and prevention of cardioembolic stroke in patients at the extremes of body weight and provides guidance regarding agent selection. Conclusion While the published evidence on use of DOACs in patients at extremes of body weight is sparse, apixaban and rivaroxaban appear to have the most favorable safety and efficacy profiles. Edoxaban and dabigatran should be avoided.

Direct Oral Anticoagulant Concentrations in Obese and High Body Weight Patients: A Cohort Study

2020 ◽  
Author(s):  
Anne Céline Martin ◽  
William Thomas ◽  
Zahra Mahir ◽  
Maeve P. Crowley ◽  
Terry Dowling ◽  
...  
Keyword(s):  
Body Weight ◽  
Creatinine Clearance ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Factor Xa ◽  
High Body Weight ◽  
High Body ◽  
Trough Concentrations ◽  
Fxa Inhibitor ◽  
Age Range

Abstract Background Direct oral anticoagulants (DOACs) are prescribed for atrial fibrillation (AF) and venous thromboembolism (VTE) and both occur more frequently in obese patients. Outcomes from DOAC trials included few individuals ≥ 120 kg leading to uncertainty whether high body weight (BW) reduces DOAC concentrations. Objectives This article investigates the relationship between factor Xa (FXa) inhibitor concentrations, BW, and renal function, and compares them in high BW patients with unselected populations. Methods Consecutive patients in two United Kingdom centers, weighing ≥ 120 kg receiving 5 mg twice daily apixaban or 20 mg once daily rivaroxaban for AF or VTE were prospectively included. Peak or trough concentrations were measured using specific chromogenic assays, expressed in mean or median (5th–95th percentiles). On-therapy range was the interval from the 5th percentile trough concentration to the 95th percentile peak concentration. Results One hundred patients were included; age range: 23 to 78 years, 31% were women, 58% had AF, creatinine clearance range: 67 to 474 mL/min. Median BW was 139 kg, and 84% had body mass index (BMI) ≥ 40 kg/m2. DOAC peak and trough concentrations varied from 44 to 727 and 14 to 299 ng/mL, respectively. There was no linear relationship between FXa inhibitor concentrations at peak or trough and BW or BMI, and creatinine clearance. Apixaban troughs in AF and rivaroxaban peaks in VTE were lower than in unselected populations. However, only two trough concentrations were below the expected range, and 109/116 were within the on-therapy range. Conclusion These data indicated that obese or high BW patients generally achieve therapeutic FXa inhibitor concentrations. However, further investigations assessing clinical outcomes are required.

460Edoxaban versus warfarin in atrial fibrillation patients with low, mid and high body weight: analysis of outcomes in the engage AF TIMI 48 trial

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
G Boriani ◽  
C T Ruff ◽  
J F Kuder ◽  
M Shi ◽  
H Lanz ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Body Weight ◽  
Major Bleeding ◽  
Oral Anticoagulants ◽  
Clinical Status ◽  
Similar Efficacy ◽  
Relative Reduction ◽  
High Body Weight ◽  
High Body ◽  
The Impact

Abstract Background The impact on outcomes of oral anticoagulants in pts at extremes of body weight have not been well-characterized. Aim To analyse the outcomes of pts with atrial fibrillation (AF) enrolled in ENGAGE AF-TMI 48 randomized to warfarin (W) targeting INR 2.0–3.0, higher (HDE) or lower dose regimens of edoxaban (LDE), focusing on subgroups of patients at the extremes of weight. Methods and results Among 21105 pts enrolled in the trial we identified 3 subgroups: 1082 with low body weight (LBW) (<5th percentile, <55kg), 2153 with mid body weight (MBW) (45–55th percentile, 80–84 kg), and 1093 patients with high body weight (HBE) (>95th percentile, >120 kg). Baseline characteristics differed markedly (LWB pts were older and more likely Asian, women, with prior TIA/stroke, renal dysfunction) resulting in a trend towards higher rates of stroke/systemic embolism (SSE: 6.5% vs 4.7% in MBW vs 1.6% in HBW) and major bleeding (MB: 9.3% vs 7.7% in MBW vs 6.5% in HBW) in the warfarin arm. The risks of SSE (Pint = 0.52) were similar between W and HDE regardless of body weight, while the relative reduction in MB was greatest in LBW patients (HR reduction45%, 23%, 1% across weight groups; Pint = 0.35) (Figure). Net clinical outcomes (SEE/major bleeding/death) tended to be most favourable for LBW pts (HR 0.67 [0.50–0.90]; Pint 0.084) (Figure). Main outcomes during follow up Conclusions In ENGAGE AF-TIMI 48 the profile of AF pts with LBW markedly differed suggesting a more fragile clinical status. Use of dose-adjusted edoxaban, as compared to W, was associated with similar efficacy regardless of weight, while bleeding and net outcomes were most favourable in LBW pts.

Impact of weight on the efficacy and safety of direct-acting oral anticoagulants in patients with non-valvular atrial fibrillation: a meta-analysis

EP Europace ◽  
2020 ◽  
Vol 22 (3) ◽  
pp. 361-367 ◽  
Author(s):  
Aaqib H Malik ◽  
Srikanth Yandrapalli ◽  
Suchith Shetty ◽  
Wilbert S Aronow ◽  
Diwakar Jain ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Major Bleeding ◽  
Oral Anticoagulants ◽  
Outcome Data ◽  
Phase Iii ◽  
Safety And Efficacy ◽  
Low Bmi ◽  
Direct Acting ◽  
The Impact ◽  
Direct Acting Oral Anticoagulants

Abstract Aims This study sought to determine the impact of weight and body mass index (BMI) on the safety and efficacy of direct-acting oral anticoagulants (DOACs) compared with warfarin in patients with non-valvular atrial fibrillation. Methods and results A systematic literature search was employed in PubMed, Embase, and Cochrane clinical trials with no language or date restrictions. Randomized trials or their substudies were assessed for relevant outcome data for efficacy that included stroke or systemic embolization (SSE), and safety including major bleeding and all-cause mortality. Binary outcome data and odds ratios from the relevant articles were used to calculate the pooled relative risk. For SSE, the data from the four Phase III trials showed that DOACs are better or similarly effective with low BMI 0.73 (0.56–0.97), normal BMI 0.72 (0.58–0.91), overweight 0.87 (0.76–0.99), and obese 0.87 (0.76–1.00). The risk of major bleeding was also better or similar with DOACs in all BMI subgroups with low BMI 0.62 (0.37–1.05), normal BMI 0.72 (0.58–0.90), overweight 0.83 (0.71–0.96), and obese 0.91 (0.81–1.03). There was no impact on mortality in all the subgroups. In a meta-regression analysis, the effect size advantage of DOACs compared with warfarin in terms of safety and efficacy gradually attenuated with increasing weight. Conclusion Our findings suggest that a weight-based dosage adjustment may be necessary to achieve optimal benefits of DOACs for thromboembolic prevention in these patients with non-valvular atrial fibrillation. Further dedicated trials are needed to confirm these findings. PROSPERO 2019 CRD42019140693. Available from: https://www.crd.york.ac.uk/prospero/display_record.php? ID=CRD42019140693.

Genetic variation in a line of mice selected to its limit for high body weight

1974 ◽  
Vol 19 (3) ◽  
pp. 273-289 ◽  
Author(s):  
W. K. Al-Murrani ◽  
R. C. Roberts
Keyword(s):  
Body Weight ◽  
Genetic Variance ◽  
Genetic Model ◽  
Random Mating ◽  
Inbred Lines ◽  
High Body Weight ◽  
High Body ◽  
Lower Body Weight ◽  
Recessive Genes ◽  
Selection For

SUMMARYA line of mice, at its limit to selection for high body weight did not decline in performance over 11 generations of random mating, neither did it respond when selection was renewed. The experiment tested a method of improving body weight by a scheme which had earlier increased litter size under similar circumstances. The scheme was to derive partially inbred lines from the plateaued line, to select during inbreeding and, finally, to cross the best inbreds. Body weight was not increased, but the study allowed further examination of the residual genetic variance in the line.During inbreeding, the inbred lines became clearly differentiated in body weight, proving that loci controlling body weight had not become fixed. There was also a significant response to selection for a lower body weight during inbreeding. The pattern of results suggested the segregation of recessive genes, detrimental to high body weight but which selection had become inefficient at removing. A genetic model compatible with the results accommodated several such recessives, perhaps as many as 10, each with an effect of about two-thirds of a standard deviation (or some equivalent combination of gene number and effect), and at frequencies of around 0·2. Nevertheless, the total improvement in body weight to be gained by their elimination was only half a gram, or less than 2 %. Thus, substantial genetic effects can occur at individual loci despite trivially low heritabilities and negligible potential gains.

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