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Semin Respir Crit Care Med 2021; 42(02): 233-249
DOI: 10.1055/s-0041-1723952
Review Article

Direct Oral Anticoagulants in the Treatment of Venous Thromboembolism: Use in Patients with Advanced Renal Impairment, Obesity, or Other Weight-Related Special Populations

Paul P. Dobesh
1   College of Pharmacy, University of Nebraska Medical Center, Nebraska Medical Center, Omaha, Nebraska
,
Molly M. Kernan
1   College of Pharmacy, University of Nebraska Medical Center, Nebraska Medical Center, Omaha, Nebraska
,
Jenni J. Lueshen
1   College of Pharmacy, University of Nebraska Medical Center, Nebraska Medical Center, Omaha, Nebraska
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Abstract

There are currently more than 7 million patients taking a direct oral anticoagulant (DOAC), with more new prescriptions per year than warfarin. Despite impressive efficacy and safety data for the treatment of venous thromboembolism, patients with obesity or advanced renal impairment represented a small portion of the patients enrolled in the phase 3 clinical trials. Therefore, to evaluate the potential use of DOACs in these special populations, clinicians need to have an understanding of the pharmacokinetics and pharmacodynamics of these agents in these settings. Since data from randomized controlled trials are limited, data from observational trials are helpful in gaining comfort with the use of DOACs in these special populations. Selecting the appropriate dose for each agent is imperative in achieving optimal patient outcomes. We provide an extensive review of the pharmacokinetics, pharmacodynamics, phase 3 clinical trials, and observational studies on the use of DOACs in patients with advanced renal impairment, obesity, or other weight-related special populations to provide clinicians with a comprehensive understanding of the data for optimal drug and dose selection.

Keywords

DOAC - NOAC - obesity - venous thromboembolism - renal impairment - renal dysfunction


Publication History

Article published online:
18 February 2021

© 2021. Thieme. All rights reserved.

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  • References

  • 1 Kearon C, Akl EA, Ornelas J. et al. Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report. Chest 2016; 149 (02) 315-352
    CrossrefPubMedGoogle Scholar
  • 2 Schünemann HJ, Cushman M, Burnett AE. et al. American Society of Hematology 2018 guidelines for management of venous thromboembolism: prophylaxis for hospitalized and nonhospitalized medical patients. Blood Adv 2018; 2 (22) 3198-3225
    CrossrefPubMedGoogle Scholar
  • 3 Hill NR, Fatoba ST, Oke JL. et al. Global prevalence of chronic kidney disease - a systematic review and meta-analysis. PLoS One 2016; 11 (07) e0158765
    CrossrefPubMedGoogle Scholar
  • 4 Levin A, Stevens PE, Bilous RW. et al. KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl 2013; 3 DOI: 10.1038/kisup.2012.74.
    CrossrefPubMedGoogle Scholar
  • 5 Food and Drug Administration. Guidance for industry pharmacokinetics in patients with impaired renal function—study design, data analysis, and impact on dosing and labeling. Accessed November 24, 2020 at: https://www.fda.gov/media/71334/download
    Google Scholar
  • 6 National Institute of Diabetes and Digestive and Kidney Diseases. Kidney disease statistics for the United States. Accessed November 24, 2020 at: https://www.niddk.nih.gov/health-information/health-statistics/kidney-disease
    Google Scholar
  • 7 Cheung KL, Zakai NA, Folsom AR. et al. Measures of kidney disease and the risk of venous thromboembolism in the REGARDS (Reasons for Geographic and Racial Differences in Stroke) study. Am J Kidney Dis 2017; 70 (02) 182-190
    CrossrefPubMedGoogle Scholar
  • 8 Wattanakit K, Cushman M, Stehman-Breen C, Heckbert SR, Folsom AR. Chronic kidney disease increases risk for venous thromboembolism. J Am Soc Nephrol 2008; 19 (01) 135-140
    CrossrefPubMedGoogle Scholar
  • 9 Bowie M, Valencia V, Perez-Alvarez I, Tran M-H. Safety analysis of apixaban versus warfarin in patients with advanced kidney disease. J Thromb Thrombolysis 2018; 46 (02) 246-252
    CrossrefPubMedGoogle Scholar
  • 10 Bonde AN, Lip GYH, Kamper AL. et al. Renal function, time in therapeutic range and outcomes in warfarin-treated atrial fibrillation patients: a retrospective analysis of nationwide registries. Thromb Haemost 2017; 117 (12) 2291-2299
    Article in Thieme ConnectPubMedGoogle Scholar
  • 11 Shah M, Avgil Tsadok M, Jackevicius CA. et al. Warfarin use and the risk for stroke and bleeding in patients with atrial fibrillation undergoing dialysis. Circulation 2014; 129 (11) 1196-1203
    CrossrefPubMedGoogle Scholar
  • 12 Lin MC, Streja E, Soohoo M. et al. Warfarin use and increased mortality in end stage renal disease. Am J Nephrol 2017; 46 (04) 249-256
    CrossrefPubMedGoogle Scholar
  • 13 Randhawa MS, Vishwanath R, Rai MP. et al. Association between use of warfarin for atrial fibrillation and outcomes among patients with end-stage renal disease: a systematic review and meta-analysis. JAMA Netw Open 2020; 3 (04) e202175
    CrossrefPubMedGoogle Scholar
  • 14 PRADAXA® (dabigatran etexilate mesylate). Full Prescribing Information. Ridgefield, CT, USA: Boehringer Ingelheim Pharmaceuticals, Inc.; 2015
    Google Scholar
  • 15 XARELTO® (rivaroxaban) tablets. Full Prescribing Information. Titusville, NJ, USA: Janssen Pharmaceuticals; 2016
    Google Scholar
  • 16 ELIQUIS® (apixaban) tablets for oral use. Full Prescribing Information. Princeton, NJ, USA, and NY, NY, USA: Bristol-Myers Squibb Company and Pfizer Inc; 2016
    Google Scholar
  • 17 SAVAYSA® (edoxaban) tablets for oral use. Full Prescribing Information. Parsippany, NJ, USA: Daiichi Sankyo Inc.; 2015
    Google Scholar
  • 18 Stangier J, Rathgen K, Stähle H, Mazur D. Influence of renal impairment on the pharmacokinetics and pharmacodynamics of oral dabigatran etexilate: an open-label, parallel-group, single-centre study. Clin Pharmacokinet 2010; 49 (04) 259-268
    CrossrefPubMedGoogle Scholar
  • 19 Wilson JAS, Goralski KB, Soroka SD. et al. An evaluation of oral dabigatran etexilate pharmacokinetics and pharmacodynamics in hemodialysis. J Clin Pharmacol 2014; 54 (08) 901-909
    CrossrefPubMedGoogle Scholar
  • 20 Hariharan S, Madabushi R. Clinical pharmacology basis of deriving dosing recommendations for dabigatran in patients with severe renal impairment. J Clin Pharmacol 2012; 52 (1, Suppl): 119S-125S
    CrossrefPubMedGoogle Scholar
  • 21 Lehr T, Haertter S, Liesenfeld KH. et al. Dabigatran etexilate in atrial fibrillation patients with severe renal impairment: dose identification using pharmacokinetic modeling and simulation. J Clin Pharmacol 2012; 52 (09) 1373-1378
    CrossrefPubMedGoogle Scholar
  • 22 Kooiman J, van der Hulle T, Maas H. et al. Pharmacokinetics and pharmacodynamics of dabigatran 75 mg b.i.d. in patients with severe chronic kidney disease. J Am Coll Cardiol 2016; 67 (20) 2442-2444
    CrossrefPubMedGoogle Scholar
  • 23 Kubitza D, Becka M, Mueck W. et al. Effects of renal impairment on the pharmacokinetics, pharmacodynamics and safety of rivaroxaban, an oral, direct factor Xa inhibitor. Br J Clin Pharmacol 2010; 70 (05) 703-712
    CrossrefPubMedGoogle Scholar
  • 24 Dias C, Moore KT, Murphy J. et al. Pharmacokinetics, pharmacodynamics, and safety of single-dose rivaroxaban in chronic hemodialysis. Am J Nephrol 2016; 43 (04) 229-236
    CrossrefPubMedGoogle Scholar
  • 25 De Vriese AS, Caluwé R, Bailleul E. et al. Dose-finding study of rivaroxaban in hemodialysis patients. Am J Kidney Dis 2015; 66 (01) 91-98
    CrossrefPubMedGoogle Scholar
  • 26 Chang M, Yu Z, Shenker A. et al. Effect of renal impairment on the pharmacokinetics, pharmacodynamics, and safety of apixaban. J Clin Pharmacol 2016; 56 (05) 637-645
    CrossrefPubMedGoogle Scholar
  • 27 Wang X, Tirucherai G, Marbury TC. et al. Pharmacokinetics, pharmacodynamics, and safety of apixaban in subjects with end-stage renal disease on hemodialysis. J Clin Pharmacol 2016; 56 (05) 628-636
    CrossrefPubMedGoogle Scholar
  • 28 Mavrakanas TA, Samer CF, Nessim SJ, Frisch G, Lipman ML. Apixaban pharmacokinetics at steady state in hemodialysis patients. J Am Soc Nephrol 2017; 28 (07) 2241-2248
    CrossrefPubMedGoogle Scholar
  • 29 Parasrampuria DA, Truitt KE. Pharmacokinetics and pharmacodynamics of edoxaban, a non-vitamin K antagonist oral anticoagulant that inhibits clotting factor Xa. Clin Pharmacokinet 2016; 55 (06) 641-655
    CrossrefPubMedGoogle Scholar
  • 30 Yin OQP, Tetsuya K, Miller R. Edoxaban population pharmacokinetics and exposure-response analysis in patients with non-valvular atrial fibrillation. Eur J Clin Pharmacol 2014; 70 (11) 1339-1351
    CrossrefPubMedGoogle Scholar
  • 31 Parasrampuria DA, Marbury T, Matsushima N. et al. Pharmacokinetics, safety, and tolerability of edoxaban in end-stage renal disease subjects undergoing haemodialysis. Thromb Haemost 2015; 113 (04) 719-727
    Article in Thieme ConnectPubMedGoogle Scholar
  • 32 Schulman S, Kearon C, Kakkar AK. et al; RE-COVER Study Group. Dabigatran versus warfarin in the treatment of acute venous thromboembolism. N Engl J Med 2009; 361 (24) 2342-2352
    CrossrefPubMedGoogle Scholar
  • 33 Schulman S, Kakkar AK, Goldhaber SZ. et al; RE-COVER II Trial Investigators. Treatment of acute venous thromboembolism with dabigatran or warfarin and pooled analysis. Circulation 2014; 129 (07) 764-772
    CrossrefPubMedGoogle Scholar
  • 34 Goldhaber SZ, Schulman S, Eriksson H. et al. Dabigatran versus warfarin for acute venous thromboembolism in elderly or impaired renal function patients: pooled analysis for RE-COVER and RE-COVER II. Thromb Haemost 2017; 117 (11) 2045-2052
    Article in Thieme ConnectPubMedGoogle Scholar
  • 35 Bauersachs R, Berkowitz SD, Brenner B. et al; EINSTEIN Investigators. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med 2010; 363 (26) 2499-2510
    CrossrefPubMedGoogle Scholar
  • 36 Büller HR, Prins MH, Lensin AW. et al; EINSTEIN–PE Investigators. Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med 2012; 366 (14) 1287-1297
    CrossrefPubMedGoogle Scholar
  • 37 Prins MH, Lensing AWA, Bauersachs R. et al; EINSTEIN Investigators. Oral rivaroxaban versus standard therapy for the treatment of symptomatic venous thromboembolism: a pooled analysis of the EINSTEIN-DVT and PE randomized studies. Thromb J 2013; 11 (01) 21
    CrossrefPubMedGoogle Scholar
  • 38 Bauersachs RM, Lensing AWA, Prins MH. et al. Rivaroxaban versus enoxaparin/vitamin K antagonist therapy in patients with venous thromboembolism and renal impairment. Thromb J 2014; 12: 25
    CrossrefPubMedGoogle Scholar
  • 39 Agnelli G, Buller HR, Cohen A. et al; AMPLIFY Investigators. Oral apixaban for the treatment of acute venous thromboembolism. N Engl J Med 2013; 369 (09) 799-808
    CrossrefPubMedGoogle Scholar
  • 40 Büller HR, Décousus H, Grosso MA. et al; Hokusai-VTE Investigators. Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism. N Engl J Med 2013; 369 (15) 1406-1415
    CrossrefPubMedGoogle Scholar
  • 41 Fanikos J, Burnett AE, Mahan CE, Dobesh PP. Renal function and direct oral anticoagulant treatment for venous thromboembolism. Am J Med 2017; 130 (10) 1137-1143
    CrossrefPubMedGoogle Scholar
  • 42 Gaertner S, Cordeanu E-M, Nouri S. et al. Rivaroxaban versus standard anticoagulation for symptomatic venous thromboembolism (REMOTEV observational study): analysis of 6-month outcomes. Int J Cardiol 2017; 226: 103-109
    CrossrefPubMedGoogle Scholar
  • 43 Reed D, Palkimas S, Hockman R, Abraham S, Le T, Maitland H. Safety and effectiveness of apixaban compared to warfarin in dialysis patients. Res Pract Thromb Haemost 2018; 2 (02) 291-298
    CrossrefPubMedGoogle Scholar
  • 44 Sarratt SC, Nesbit R, Moye R. Safety outcomes of apixaban compared with warfarin in patients with end-stage renal disease. Ann Pharmacother 2017; 51 (06) 445-450
    CrossrefPubMedGoogle Scholar
  • 45 Schafer JH, Casey AL, Dupre KA, Staubes BA. Safety and efficacy of apixaban versus warfarin in patients with advanced chronic kidney disease. Ann Pharmacother 2018; 52 (11) 1078-1084
    CrossrefPubMedGoogle Scholar
  • 46 Stanton BE, Barasch NS, Tellor KB. Comparison of the safety and effectiveness of apixaban versus warfarin in patients with severe renal impairment. Pharmacotherapy 2017; 37 (04) 412-419
    CrossrefPubMedGoogle Scholar
  • 47 Hanni C, Petrovitch E, Ali M. et al. Outcomes associated with apixaban vs warfarin in patients with renal dysfunction. Blood Adv 2020; 4 (11) 2366-2371
    CrossrefPubMedGoogle Scholar
  • 48 Herndon K, Guidry TJ, Wassell K, Elliott W. Characterizing the safety profile of apixaban versus warfarin in moderate to severe chronic kidney disease at a Veterans Affairs hospital. Ann Pharmacother 2020; 54 (06) 554-560
    CrossrefPubMedGoogle Scholar
  • 49 Siontis KC, Zhang X, Eckard A. et al. Outcomes associated with apixaban use in patients with end-stage kidney disease and atrial fibrillation in the United States. Circulation 2018; 138 (15) 1519-1529
    CrossrefPubMedGoogle Scholar
  • 50 Chan KE, Edelman ER, Wenger JB, Thadhani RI, Maddux FW. Dabigatran and rivaroxaban use in atrial fibrillation patients on hemodialysis. Circulation 2015; 131 (11) 972-979
    CrossrefPubMedGoogle Scholar
  • 51 Di Lullo L, Tripepi G, Ronco C. et al. Safety and effectiveness of rivaroxaban and warfarin in moderate-to-advanced CKD: real world data. J Nephrol 2018; 31 (05) 751-756
    CrossrefPubMedGoogle Scholar
  • 52 Weir MR, Berger JS, Ashton V. et al. Impact of renal function on ischemic stroke and major bleeding rates in nonvalvular atrial fibrillation patients treated with warfarin or rivaroxaban: a retrospective cohort study using real-world evidence. Curr Med Res Opin 2017; 33 (10) 1891-1900
    CrossrefPubMedGoogle Scholar
  • 53 Weir MR, Ashton V, Moore KT, Shrivastava S, Peterson ED, Ammann EM. Rivaroxaban versus warfarin in patients with nonvalvular atrial fibrillation and stage IV-V chronic kidney disease. Am Heart J 2020; 223: 3-11
    CrossrefPubMedGoogle Scholar
  • 54 Coleman CI, Kreutz R, Sood NA. et al. Rivaroxaban versus warfarin in patients with nonvalvular atrial fibrillation and severe kidney diseases or undergoing hemodialysis. Am J Med 2019; 132 (09) 1078-1083
    CrossrefPubMedGoogle Scholar
  • 55 Miao B, Sood N, Bunz TJ, Coleman CI. Rivaroxaban versus apixaban in non-valvular atrial fibrillation patients with end-stage renal disease or receiving dialysis. Eur J Haematol 2020; 104 (04) 328-335
    CrossrefPubMedGoogle Scholar
  • 56 Fazio G, Dentamaro I, Gambacurta R, Alcamo P, Colonna P. Safety of edoxaban 30 mg in elderly patients with severe renal impairment. Clin Drug Investig 2018; 38 (11) 1023-1030
    CrossrefPubMedGoogle Scholar
  • 57 Ashley J, McArthur E, Bota S. et al. Risk of cardiovascular events and mortality among elderly patients with reduced GFR receiving direct oral anticoagulants. Am J Kidney Dis 2020; 76 (03) 311-320
    CrossrefPubMedGoogle Scholar
  • 58 Yao X, Inselman JW, Ross JS. et al. Comparative effectiveness and safety of oral anticoagulants across kidney function in patients with atrial fibrillation. Circ Cardiovasc Qual Outcomes 2020; 13 (10) e006515
    PubMedGoogle Scholar
  • 59 Coleman CI, Kreutz R, Sood N. et al. Rivaroxaban's impact on renal decline in patients with nonvalvular atrial fibrillation: a US MarketScan claims database analysis. Clin Appl Thromb Hemost 2019; 25: 1076029619868535
    Google Scholar
  • 60 Pastori D, Ettorre E, Lip GYH. et al. Association of different oral anticoagulants use with renal function worsening in patients with atrial fibrillation: a multicentre cohort study. Br J Clin Pharmacol 2020; 86 (12) 2455-2463
    CrossrefPubMedGoogle Scholar
  • 61 Miyazawa K, Pastori D, Lip GYH. Changes in renal function in patients with atrial fibrillation: Efficacy and safety of the non-vitamin K antagonist oral anticoagulants. Am Heart J 2018; 198: 166-168
    CrossrefPubMedGoogle Scholar
  • 62 Nabiee M, Dashti-Khavidaki S, Khajeh B. Dose discordance of direct acting oral anticoagulants using different equations for estimating GFR: a literature review. Exp Rev Clin Pharm 2020; 13 (08) 857-863
    CrossrefPubMedGoogle Scholar
  • 63 Schwartz JB. Potential effect of substituting estimated glomerular filtration rate for estimated creatinine clearance for dosing of direct oral anticoagulants. J Am Geriatr Soc 2016; 64 (10) 1996-2002
    CrossrefPubMedGoogle Scholar
  • 64 World Health Organization. Overweight and obesity. Accessed November 20, 2020 at: https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight
    Google Scholar
  • 65 NHLBI Obesity Education Initiative. The Practical Guide: Identification, Evaluation, and Treatment of Overweight and Obesity in Adults. Accessed November 24, 2020 at: https://www.nhlbi.nih.gov/files/docs/guidelines/prctgd_c.pdf
    Google Scholar
  • 66 Centers for Disease Control and Prevention. Defining adult overweight and obesity. Accessed November 24, 2020 at: https://www.cdc.gov/obesity/adult/defining.html
    Google Scholar
  • 67 Virani SS, Alonso A, Benjamin EJ. et al; American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics – 2020 update: a report from the American Heart Association. Circulation 2020; 141 (09) e139-e596
    CrossrefPubMedGoogle Scholar
  • 68 Freeman AL, Pendleton RC, Rondina MT. Prevention of venous thromboembolism in obesity. Expert Rev Cardiovasc Ther 2010; 8 (12) 1711-1721
    CrossrefPubMedGoogle Scholar
  • 69 Martin K, Beyer-Westendorf J, Davidson BL, Huisman MV, Sandset PM, Moll S. Use of the direct oral anticoagulants in obese patients: guidance from the SSC of the ISTH. J Thromb Haemost 2016; 14 (06) 1308-1313
    CrossrefPubMedGoogle Scholar
  • 70 Wallace JL, Reaves AB, Tolley EA. et al. Comparison of initial warfarin response in obese patients versus non-obese patients. J Thromb Thrombolysis 2013; 36 (01) 96-101
    CrossrefPubMedGoogle Scholar
  • 71 Tellor KB, Nguyen SN, Bultas AC, Armbruster AL, Greenwald NA, Yancey AM. Evaluation of the impact of body mass index on warfarin requirements in hospitalized patients. Ther Adv Cardiovasc Dis 2018; 12 (08) 207-216
    CrossrefPubMedGoogle Scholar
  • 72 Ogunsua AA, Touray S, Lui JK, Ip T, Escobar JV, Gore J. Body mass index predicts major bleeding risks in patients on warfarin. J Thromb Thrombolysis 2015; 40 (04) 494-498
    CrossrefPubMedGoogle Scholar
  • 73 Tittl L, Endig S, Marten S, Reitter A, Beyer-Westendorf I, Beyer-Westendorf J. Impact of BMI on clinical outcomes of NOAC therapy in daily care - results of the prospective Dresden NOAC Registry (NCT01588119). Int J Cardiol 2018; 262: 85-91
    CrossrefPubMedGoogle Scholar
  • 74 Kubitza D, Becka M, Zuehlsdorf M, Mueck W. Body weight has limited influence on the safety, tolerability, pharmacokinetics, or pharmacodynamics of rivaroxaban (BAY 59-7939) in healthy subjects. J Clin Pharmacol 2007; 47 (02) 218-226
    CrossrefPubMedGoogle Scholar
  • 75 Mueck W, Lensing AWA, Agnelli G, Decousus H, Prandoni P, Misselwitz F. Rivaroxaban: population pharmacokinetic analyses in patients treated for acute deep-vein thrombosis and exposure simulations in patients with atrial fibrillation treated for stroke prevention. Clin Pharmacokinet 2011; 50 (10) 675-686
    CrossrefPubMedGoogle Scholar
  • 76 Barsam SJ, Patel JP, Roberts LN. et al. The impact of body weight on rivaroxaban pharmacokinetics. Res Pract Thromb Haemost 2017; 1 (02) 180-187
    CrossrefPubMedGoogle Scholar
  • 77 Speed V, Green B, Roberts LN. et al. Fixed dose rivaroxaban can be used in extremes of bodyweight: a population pharmacokinetic analysis. J Thromb Haemost 2020; 18 (09) 2296-2307
    CrossrefPubMedGoogle Scholar
  • 78 Arachchillage D, Reynolds R, Devey T, Maclean R, Kitchen S, van Veen JJ. Effect of extremes of body weight on drug level in patient treated with standard dose of rivaroxaban for venous thromboembolism; real life experience. Thromb Res 2016; 147: 32-35
    CrossrefPubMedGoogle Scholar
  • 79 Upreti VV, Wang J, Barrett YC. et al. Effect of extremes of body weight on the pharmacokinetics, pharmacodynamics, safety and tolerability of apixaban in healthy subjects. Br J Clin Pharmacol 2013; 76 (06) 908-916
    CrossrefPubMedGoogle Scholar
  • 80 Wasan SM, Feland N, Grant R, Aston CE. Validation of apixaban anti-factor Xa assay and impact of body weight. Thromb Res 2019; 182: 51-55
    CrossrefPubMedGoogle Scholar
  • 81 Borst JM, van Rein N, Bakker ECMD. et al. Body weight is negatively associated with direct oral anticoagulant trough concentrations in dabigatran and apixaban users. Br J Haematol 2020; ; (epub ahead of print) DOI: 10.1111/bjh.17009.
    CrossrefPubMedGoogle Scholar
  • 82 Di Minno MND, Lupoli R, Di Minno A, Ambrosino P, Scalera A, Dentali F. Effect of body weight on efficacy and safety of direct oral anticoagulants in the treatment of patients with acute venous thromboembolism: a meta-analysis of randomized controlled trials. Ann Med 2015; 47 (01) 61-68
    CrossrefPubMedGoogle Scholar
  • 83 Patil T, Lebrecht M. A single center retrospective cohort study evaluating use of direct oral anticoagulants (DOACs) in morbidly obese veteran population. Thromb Res 2020; 192: 124-130
    CrossrefPubMedGoogle Scholar
  • 84 Wysokinski WE, Froehling DA, Houghton DE. et al. Effectiveness and safety of apixaban and rivaroxaban for acute venous thromboembolism therapy in patients with extremes in bodyweight. Eur J Haematol 2020; 105 (04) 484-494
    CrossrefPubMedGoogle Scholar
  • 85 Coons JC, Albert L, Bejjani A, Iasella CJ. Effectiveness and safety of direct oral anticoagulants versus warfarin in obese patients with acute venous thromboembolism. Pharmacotherapy 2020; 40 (03) 204-210
    CrossrefPubMedGoogle Scholar
  • 86 Kushnir M, Choi Y, Eisenberg R. et al. Efficacy and safety of direct oral factor Xa inhibitors compared with warfarin in patients with morbid obesity: a single-centre, retrospective analysis of chart data. Lancet Haematol 2019; 6 (07) e359-e365
    Google Scholar
  • 87 Spyropoulos AC, Ashton V, Chen YW, Wu B, Peterson ED. Rivaroxaban versus warfarin treatment among morbidly obese patients with venous thromboembolism: comparative effectiveness, safety, and costs. Thromb Res 2019; 182: 159-166
    CrossrefPubMedGoogle Scholar
  • 88 Perales IJ, San Agustin K, DeAngelo J, Campbell AM. Rivaroxaban versus warfarin for stroke prevention and venous thromboembolism treatment in extreme obesity and high body weight. Ann Pharmacother 2020; 54 (04) 344-350
    CrossrefPubMedGoogle Scholar
  • 89 Quan S, Smith J, Wu C, Koshman SL, Nguyen B, Bungard TJ. Anticoagulant therapies and outcomes in obese patients with acute venous thromboembolism. Thromb Res 2020; 187: 56-62
    CrossrefPubMedGoogle Scholar
  • 90 Sa RA, Al-Ani F, Lazo-Langner A, Louzada ML. Efficacy and safety of direct oral anticoagulants in obese patients with venous thromboembolism. Blood 2019; 134 (Suppl. 01) 3675
    CrossrefPubMedGoogle Scholar
  • 91 Costa OS, Beyer-Westendorf J, Ashton V. et al. Effectiveness and safety of rivaroxaban versus warfarin in obese patients with acute venous thromboembolism: analysis of electronic health record data. J Thromb Thrombolysis 2020; ; (epub ahead of print) DOI: 10.1007/s11239-020-021990.
    CrossrefPubMedGoogle Scholar
  • 92 Doucette K, Latif H, Vakiti A, Tefera E, Patel B, Fitzpatrick K. Efficacy and safety of direct-acting oral anticoagulants (DOACs) in the overweight and obese. Adv Hematol 2020; 2020: 3890706
    PubMedGoogle Scholar
  • 93 Elshafei MN, Mohamed MFH, El-Bardissy A. et al. Comparative effectiveness and safety of direct oral anticoagulants compared to warfarin in morbidly obese patients with acute venous thromboembolism: systematic review and a meta-analysis. J Thromb Thrombolysis 2020; ; (epub ahead of print) DOI: 10.1007/s11239-020-021179-4.
    CrossrefPubMedGoogle Scholar
  • 94 Kido K, Shimizu M, Shiga T, Hashiguchi M. Meta-analysis comparing direct oral anticoagulants versus warfarin in morbidly obese patients with atrial fibrillation. Am J Cardiol 2020; 126: 23-28
    CrossrefPubMedGoogle Scholar
  • 95 Costa OS, Beyer-Westendorf J, Ashton V. et al. Effectiveness and safety of rivaroxaban versus warfarin in obese nonvalvular atrial fibrillation patients: analysis of electronic health record data. Curr Med Res Opin 2020; 36 (07) 1081-1088
    CrossrefPubMedGoogle Scholar
  • 96 Martin KA, Lee CR, Farrell TM, Moll S. Oral anticoagulant use after bariatric surgery: a literature review and clinical guidance. Am J Med 2017; 130 (05) 517-524
    CrossrefPubMedGoogle Scholar
  • 97 Thomas Z, Bareket Y, Bennett W. Rivaroxaban use following bariatric surgery. J Thromb Thrombolysis 2014; 38 (01) 90-91
    CrossrefPubMedGoogle Scholar
  • 98 Kröll D, Stirnimann G, Vogt A. et al. Pharmacokinetics and pharmacodynamics of single doses of rivaroxaban in obese patients prior to and after bariatric surgery. Br J Clin Pharmacol 2017; 83 (07) 1466-1475
    CrossrefPubMedGoogle Scholar
  • 99 Kröll D, Nett PC, Borbély YM. et al. The effect of bariatric surgery on the direct oral anticoagulant rivaroxaban: the extension study. Surg Obes Relat Dis 2018; 14 (12) 1890-1896
    CrossrefPubMedGoogle Scholar
  • 100 Mahlmann A, Gehrisch S, Beyer-Westendorf J. Pharmacokinetics of rivaroxaban after bariatric surgery: a case report. J Thromb Thrombolysis 2013; 36 (04) 533-535
    CrossrefPubMedGoogle Scholar
  • 101 Rottenstreich A, Barkai A, Arad A, Raccah BH, Kalish Y. The effect of bariatric surgery on direct-acting oral anticoagulant drug levels. Thromb Res 2018; 163: 190-195
    CrossrefPubMedGoogle Scholar
  • 102 Lee D, DeFilipp Z, Judson K, Kennedy M. Subtherapeutic anticoagulation with dabigatran following Roux-en-Y gastric bypass surgery. J Cardiol Cases 2013; 8 (01) e49-e50
    CrossrefPubMedGoogle Scholar
  • 103 De Caterina R, Lip GYH. The non-vitamin K antagonist oral anticoagulants (NOACs) and extremes of body weight-a systematic literature review. Clin Res Cardiol 2017; 106 (08) 565-572
    CrossrefPubMedGoogle Scholar
  • 104 Dobesh PP, Terry KJ. Measuring or monitoring of novel anticoagulants: Which laboratory test to request?. Curr Emerg Hosp Med Rep 2013; 1: 208-216
    CrossrefPubMedGoogle Scholar
  • 105 Dale BJ, Chan NC, Eikelboom JW. Laboratory measurement of the direct oral anticoagulants. Br J Haematol 2016; 172 (03) 315-336
    CrossrefPubMedGoogle Scholar
  • 106 Martin K, Moll S. Direct oral anticoagulant drug level testing in clinical practice: a single institution experience. Thromb Res 2016; 143: 40-44
    CrossrefPubMedGoogle Scholar