Use of NOACS in Extremes of Body Weight

Abstract

Certain physiological phenomena in our body lead to severe changes in body weight leading to obesity. If needed, currently, there is no specific regimen for using novel oral anticoagulants (NOACs) in obese patients. It has been found that fixed doses of NOACs bring out more drug exposure to lower BMI patients, whereas it brings out lesser blood drug levels in patients with higher BMI.1 When researchers evaluated NOACs in patients with atrial fibrillation (AF) or venous thromboembolism (VTE), most randomized trials did not exclude body weight from the studies. Hence, the subgroup analysis of these trials showed no considerable difference in outcomes in obese patients.2 The International Society on Thrombosis and Haemostasis showed that NOACs are safer in patients with a body weight of ≤ 120 kg (BMI ≤40 kg/m2)  at the usual dose as compared to patients with a body weight of >120 kg (BMI >40 kg/m2).2 Several retrospective studies have shown suboptimal plasma concentrations (in 20%-28% of obese patients studied) with dabigatran and rivaroxaban compared to apixaban.3 Dose reduction is recommended for apixaban if body weight is ≤ 60 kg (in addition to age and renal function). Reduction in the dose of edoxaban is recommended due to the pharmacokinetic property of high systemic exposure in low body weight patients.4 For patients with body weight > 120 kg or BMI > 40 kg/m2, it is suggested to use rivaroxaban and apixaban, while dabigatran, edoxaban, and betrixaban should be avoided.5 For patients with a body weight <60 kg, renal function should be assessed before adjusting the dose of NOACs. These patients overestimate renal function due to lower body muscle mass. Old age and frailty should also be considered, as these factors are related to bad outcomes in patients with low body weight.6 It is suggested to use apixaban (after taking a renal impairment and age into consideration) and edoxaban with caution in low-body weight patients.7 Dabigatran serves as a less-than-ideal drug for low-body weight patients due to high systemic exposure. No conclusive data is available for rivaroxaban.8 Due to a lack of clinical interest in this population subset of extreme body weight changes, we need more data, which leads to the need for more extensive work in this domain, revealing clear answers in the future. References Abarca-Gómez L, Abdeen ZA, Hamid ZA, Abu-Rmeileh NM, Acosta-Cazares B, Acuin C, et al. Worldwide trends in body-mass index, underweight, overweight, and obesity from 1975 to 2016: a pooled analysis of 2416 population-based measurement studies in 128·9 million children, adolescents, and adults. Lancet. 2017;390(10113):2627-42. Antonopoulos AS, Oikonomou EK, Antoniades C, Tousoulis D. From the BMI paradox to the obesity paradox: the obesity-mortality association in coronary heart disease. Obes Rev. 2016;17(10):989-1000. Lavie CJ,  Milani  RV, Ventura    Obesity  and  cardiovascular  disease:  risk  factor,  paradox,  and  impact  of  weight  loss. J  Am  Coll  Cardiol. 2009;53:1925-32. The Hokusai-VTE Investigators. Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism. N Engl J Med. 2013;369:1406-15. Strazzullo P, D’Elia L, Cairella G, Garbagnati F, Cappuccio FP, Scalfi L. Excess body weight and incidence of stroke: meta-analysis of prospec- tive studies with 2 million participants. Stroke. 2010;41:e418-e426. Andersen KK,  Olsen TS. The  obesity  paradox  in  stroke:  lower  mortality  and  lower  risk  of  readmission  for  recurrent  stroke  in  obese  stroke  Int J Stroke. 2015;10:99-104.   Lavie CJ,  De  Schutter A,  Patel  DA,  Romero-Corral A, Artham  SM,  Milani  Body  composition  and  survival  in  stable  coronary  heart  disease:  impact  of  lean  mass  index  and  body  fat  in  the  "obesity  paradox."  J  Am  Coll  Cardiol. 2012;60:1374-80. Sanders P, Lau DH. Mortality paradox in obesity and atrial fibrillation. JACC Clin Electrophysiol. 2016;2:364-6.