scholarly journals Direct oral anticoagulant plasma concentrations in obese and high body weight patients: An observational study

2021 ◽  
Vol 13 (1) ◽  
pp. 164
Author(s):  
A. Martin ◽  
W. Thomas ◽  
Z. Mahir ◽  
M.P. Crowley ◽  
T. Dowling ◽  
...  
Author(s):  
Anne Céline Martin ◽  
William Thomas ◽  
Zahra Mahir ◽  
Maeve P. Crowley ◽  
Terry Dowling ◽  
...  

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.


1974 ◽  
Vol 19 (3) ◽  
pp. 273-289 ◽  
Author(s):  
W. K. Al-Murrani ◽  
R. C. Roberts

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.


2020 ◽  
Vol 77 (11) ◽  
pp. 865-876
Author(s):  
Kelly Covert ◽  
Donald L Branam

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.


Author(s):  
Wilma J Nusselder ◽  
José Rubio Valverde ◽  
Matthias Bopp ◽  
Henrik Brønnum-Hansen ◽  
Patrick Deboosere ◽  
...  

Abstract Background Persons with a lower socioeconomic position spend more years with disability, despite their shorter life expectancy, but it is unknown what the important determinants are. This study aimed to quantify the contribution to educational inequalities in years with disability of eight risk factors: father’s manual occupation, low income, few social contacts, smoking, high alcohol consumption, high body-weight, low physical exercise and low fruit and vegetable consumption. Methods We collected register-based mortality and survey-based disability and risk factor data from 15 European countries covering the period 2010–14 for most countries. We calculated years with disability between the ages of 35 and 80 by education and gender using the Sullivan method, and determined the hypothetical effect of changing the prevalence of each risk factor to the prevalence observed among high educated (‘upward levelling scenario’), using Population Attributable Fractions. Results Years with disability among low educated were higher than among high educated, with a difference of 4.9 years among men and 5.5 years among women for all countries combined. Most risk factors were more prevalent among low educated. We found the largest contributions to inequalities in years with disability for low income (men: 1.0 year; women: 1.4 year), high body-weight (men: 0.6 year; women: 1.2 year) and father’s manual occupation (men: 0.7 year; women: 0.9 year), but contributions differed by country. The contribution of smoking was relatively small. Conclusions Disadvantages in material circumstances (low income), circumstances during childhood (father’s manual occupation) and high body-weight contribute to inequalities in years with disability.


2019 ◽  
Vol 98 (10) ◽  
pp. 5137-5145 ◽  
Author(s):  
S.A.S. van der Klein ◽  
S.H. Hadinia ◽  
F.E. Robinson ◽  
G.Y. Bédécarrats ◽  
M.J. Zuidhof

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