Current status of rivaroxaban in elderly patients with pulmonary embolism (Review)
- Authors:
- Zi‑Kai Song
- Hongyan Cao
- Haidi Wu
- Qi Wei
- Minglong Tang
- Shuo Yang
- Yang Liu
- Ling Qin
-
Affiliations: Department of Cardiology, The First Hospital of Jilin University, Changchun, Jilin 130000, P.R. China - Published online on: February 26, 2020 https://doi.org/10.3892/etm.2020.8559
- Pages: 2817-2825
-
Copyright: © Song et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
This article is mentioned in:
Abstract
|
Engbers MJ, van Hylckama Vlieg A and Rosendaal FR: Venous thrombosis in the elderly: Incidence, risk factors and risk groups. J Thromb Haemost. 8:2105–2112. 2010.PubMed/NCBI View Article : Google Scholar |
|
|
Spencer FA, Gurwitz JH, Schulman S, Linkins LA, Crowther MA, Ginsberg JS, Lee AY, Saczynski JS, Anand S, Lessard D, et al: Venous thromboembolism in older adults: A community-based study. Am J Med. 127:530–537.e3. 2014.PubMed/NCBI View Article : Google Scholar |
|
|
Stein PD, Hull RD, Kayali F, Ghali WA, Alshab AK and Olson RE: Venous thromboembolism according to age: The impact of an aging population. Arch Intern Med. 164:2260–2265. 2004.PubMed/NCBI View Article : Google Scholar |
|
|
Karamichalakis N, Georgopoulos S, Vlachos K, Liatakis I, Efremidis M, Sideris A and Letsas KP: Efficacy and safety of novel anticoagulants in the elderly. J Geriatr Cardiol. 13:718–723. 2016.PubMed/NCBI View Article : Google Scholar |
|
|
Sharma M, Cornelius VR, Patel JP, Davies JG and Molokhia M: Efficacy and harms of direct oral anticoagulants in the elderly for stroke prevention in atrial fibrillation and secondary prevention of venous thromboembolism: Systematic review and meta-analysis. Circulation. 132:194–204. 2015.PubMed/NCBI View Article : Google Scholar |
|
|
Gallus A, Jackaman J, Tillett J, Mills W and Wycherley A: Safety and efficacy of warfarin started early after submassive venous thrombosis or pulmonary embolism. Lancet. 2:1293–1296. 1986.PubMed/NCBI View Article : Google Scholar |
|
|
Hirsh J: Low-molecular-weight heparin vs. Warfarin for prophylaxis against deep-vein thrombosis. N Engl J Med. 330(863)1994.PubMed/NCBI View Article : Google Scholar |
|
|
Monreal M, Foz M and Audi L: Warfarin to prevent thromboembolism in chronic atrial fibrillation. Lancet. 1:720–721. 1989.PubMed/NCBI View Article : Google Scholar |
|
|
Buller HR, Lensing AW, Prins MH, Agnelli G, Cohen A, Gallus AS, Misselwitz F, Raskob G, Schellong S and Segers A: Einstein-DVT Dose-Ranging Study investigators: A dose-ranging study evaluating once-daily oral administration of the factor Xa inhibitor rivaroxaban in the treatment of patients with acute symptomatic deep vein thrombosis: The Einstein-DVT Dose-Ranging Study. Blood. 112:2242–2247. 2008.PubMed/NCBI View Article : Google Scholar |
|
|
Scaglione F: New oral anticoagulants: Comparative pharmacology with vitamin K antagonists. Clin Pharmacokinet. 52:69–82. 2013.PubMed/NCBI View Article : Google Scholar |
|
|
EINSTEIN Investigators, Bauersachs R, Berkowitz SD, Brenner B, Buller HR, Decousus H, Gallus AS, Lensing AW, Misselwitz F, Prins MH, et al: Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med. 363:2499–2510. 2010.PubMed/NCBI View Article : Google Scholar |
|
|
EINSTEIN-PE Investigators, Büller HR, Prins MH, Lensin AW, Decousus H, Jacobson BF, Minar E, Chlumsky J, Verhamme P, Wells P, et al: Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med. 366:1287–1297. 2012.PubMed/NCBI View Article : Google Scholar |
|
|
Konstantinides SV, Torbicki A, Agnelli G, Danchin N, Fitzmaurice D, Galiè N, Gibbs JS, Huisman MV, Humbert M, Kucher N, et al: 2014 ESC guidelines on the diagnosis and management of acute pulmonary embolism. Eur Heart J. 35:3033–3069. 2014.PubMed/NCBI View Article : Google Scholar |
|
|
Mayr A, Klug G, Greulich S, Metzler B and Feuchtner G: Serpentine-like right atrial mass and fulminant bilateral pulmonary embolism during treatment with rivaroxaban. Int J Cardiovasc Imaging. 32:1001–1002. 2016.PubMed/NCBI View Article : Google Scholar |
|
|
Menichetti M, Rosso S, Menegatti E and Pazzaglia M: Use of rivaroxaban in an elderly patient with intermediate-low early mortality risk due to pulmonary embolism: A case report. J Med Case Rep. 9(274)2015.PubMed/NCBI View Article : Google Scholar |
|
|
Beckman MG, Hooper WC, Critchley SE and Ortel TL: Venous thromboembolism: A public health concern. Am J Prev Med. 38 (Suppl 4):S495–S501. 2010.PubMed/NCBI View Article : Google Scholar |
|
|
Naess IA, Christiansen SC, Romundstad P, Cannegieter SC, Rosendaal FR and Hammerstrom J: Incidence and mortality of venous thrombosis: A population-based study. J Thromb Haemost. 5:692–699. 2007.PubMed/NCBI View Article : Google Scholar |
|
|
McRae S, Tran H, Schulman S, Ginsberg J and Kearon C: Effect of patient's sex on risk of recurrent venous thromboembolism: A meta-analysis. Lancet. 368:371–378. 2006.PubMed/NCBI View Article : Google Scholar |
|
|
Spencer FA, Gore JM, Lessard D, Emery C, Pacifico L, Reed G, Gurwitz JH and Goldberg RJ: Venous thromboembolism in the elderly. A community-based perspective. Thromb Haemost. 100:780–788. 2008.PubMed/NCBI |
|
|
Ageno W, Agnelli G, Imberti D, Moia M, Palareti G, Pistelli R, Rossi R and Verso M: MASTER Investigators: Risk factors for venous thromboembolism in the elderly: Results of the master registry. Blood Coagul Fibrinolysis. 19:663–667. 2008.PubMed/NCBI View Article : Google Scholar |
|
|
Andreotti F, Rocca B, Husted S, Ajjan RA, ten Berg J, Cattaneo M, Collet JP, De Caterina R, Fox KA, Halvorsen S, et al: Antithrombotic therapy in the elderly: Expert position paper of the european society of cardiology working group on thrombosis. Eur Heart J. 36:3238–3249. 2015.PubMed/NCBI View Article : Google Scholar |
|
|
Silverstein MD, Heit JA, Mohr DN, Petterson TM, O'Fallon WM and Melton LJ III: Trends in the incidence of deep vein thrombosis and pulmonary embolism: A 25-year population-based study. Arch Intern Med. 158:585–593. 1998.PubMed/NCBI View Article : Google Scholar |
|
|
Kakkar VV, Howe CT, Flanc C and Clarke MB: Natural history of postoperative deep-vein thrombosis. Lancet. 2:230–232. 1969.PubMed/NCBI View Article : Google Scholar |
|
|
Henriksson P, Westerlund E, Wallen H, Brandt L, Hovatta O and Ekbom A: Incidence of pulmonary and venous thromboembolism in pregnancies after in vitro fertilisation: Cross sectional study. BMJ. 346(e8632)2013.PubMed/NCBI View Article : Google Scholar |
|
|
Montecucco F and Mach F: Should we focus on ‘venous vulnerability’ instead of ‘plaque vulnerability’ in symptomatic atherosclerotic patients? Thromb Haemost. 106:995–996. 2011. |
|
|
Gussoni G, Frasson S, La Regina M, Di Micco P and Monreal M: RIETE Investigators: Three-month mortality rate and clinical predictors in patients with venous thromboembolism and cancer. Findings from the RIETE registry. Thromb Res. 131:24–30. 2013.PubMed/NCBI View Article : Google Scholar |
|
|
Clayton TC, Gaskin M and Meade TW: Recent respiratory infection and risk of venous thromboembolism: Case-control study through a general practice database. Int J Epidemiol. 40:819–827. 2011.PubMed/NCBI View Article : Google Scholar |
|
|
Sweetland S, Beral V, Balkwill A, Liu B, Benson VS, Canonico M, Green J and Reeves GK: Million Women Study Collaborators: Venous thromboembolism risk in relation to use of different types of postmenopausal hormone therapy in a large prospective study. J Thromb Haemost. 10:2277–2286. 2012.PubMed/NCBI View Article : Google Scholar |
|
|
Johnson SA, Eleazer GP and Rondina MT: Pathogenesis, diagnosis, and treatment of venous thromboembolism in older adults. J Am Geriatr Soc. 64:1869–1878. 2016.PubMed/NCBI View Article : Google Scholar |
|
|
Mohebali D, Kaplan D, Carlisle M, Supiano MA and Rondina MT: Alterations in platelet function during aging: Clinical correlations with thromboinflammatory disease in older adults. J Am Geriatr Soc. 62:529–535. 2014.PubMed/NCBI View Article : Google Scholar |
|
|
van Hylckama Vlieg A and Rosendaal FR: High levels of fibrinogen are associated with the risk of deep venous thrombosis mainly in the elderly. J Thromb Haemost. 1:2677–2678. 2003.PubMed/NCBI View Article : Google Scholar |
|
|
Oger E, Lacut K, Van Dreden P, Bressollette L, Abgrall JF, Blouch MT, Scarabin PY and Mottier D: High plasma concentration of factor VIII coagulant is also a risk factor for venous thromboembolism in the elderly. Haematologica. 88:465–469. 2003.PubMed/NCBI |
|
|
Yamamoto K, Takeshita K and Saito H: Plasminogen activator inhibitor-1 in aging. Semin Thromb Hemost. 40:652–659. 2014.PubMed/NCBI View Article : Google Scholar |
|
|
Ferrucci L, Corsi A, Lauretani F, Bandinelli S, Bartali B, Taub DD, Guralnik JM and Longo DL: The origins of age-related proinflammatory state. Blood. 105:2294–2299. 2005.PubMed/NCBI View Article : Google Scholar |
|
|
Mauritz GJ, Marcus JT, Westerhof N, Postmus PE and Vonk-Noordegraaf A: Prolonged right ventricular post-systolic isovolumic period in pulmonary arterial hypertension is not a reflection of diastolic dysfunction. Heart. 97:473–478. 2011.PubMed/NCBI View Article : Google Scholar |
|
|
McIntyre KM and Sasaha AA: The hemodynamic response to pulmonary embolism in patients without prior cardiopulmonary disease. Am J Cardiol. 28:288–294. 1971.PubMed/NCBI View Article : Google Scholar |
|
|
Madhavan MV, Gersh BJ, Alexander KP, Granger CB and Stone GW: Coronary Artery Disease in Patients ≥80 Years of Age. J Am Coll Cardiol. 71:2015–2040. 2018.PubMed/NCBI View Article : Google Scholar |
|
|
Lankhaar JW, Westerhof N, Faes TJ, Marques KM, Marcus JT, Postmus PE and Vonk-Noordegraaf A: Quantification of right ventricular afterload in patients with and without pulmonary hypertension. Am J Physiol Heart Circ Physiol. 291:H1731–H1737. 2006.PubMed/NCBI View Article : Google Scholar |
|
|
Lankeit M, Jimenez D, Kostrubiec M, Dellas C, Hasenfuss G, Pruszczyk P and Konstantinides S: Predictive value of the high-sensitivity troponin T assay and the simplified Pulmonary Embolism Severity Index in hemodynamically stable patients with acute pulmonary embolism: A prospective validation study. Circulation. 124:2716–2724. 2011.PubMed/NCBI View Article : Google Scholar |
|
|
Mehta NJ, Jani K and Khan IA: Clinical usefulness and prognostic value of elevated cardiac troponin I levels in acute pulmonary embolism. Am Heart J. 145:821–825. 2003.PubMed/NCBI View Article : Google Scholar |
|
|
Burrowes KS, Clark AR and Tawhai MH: Blood flow redistribution and ventilation-perfusion mismatch during embolic pulmonary arterial occlusion. Pulm Circ. 1:365–376. 2011.PubMed/NCBI View Article : Google Scholar |
|
|
Larsson L, Grimby G and Karlsson J: Muscle strength and speed of movement in relation to age and muscle morphology. J Appl Physiol Respir Environ Exerc Physiol. 46:451–456. 1979.PubMed/NCBI View Article : Google Scholar |
|
|
Olsen H and Lanne T: Reduced venous compliance in lower limbs of aging humans and its importance for capacitance function. Am J Physiol. 275:H878–H886. 1998.PubMed/NCBI View Article : Google Scholar |
|
|
Migliacci R, Becattini C, Pesavento R, Davi G, Vedovati MC, Guglielmini G, Falcinelli E, Ciabattoni G, Dalla Valle F, Prandoni P, et al: Endothelial dysfunction in patients with spontaneous venous thromboembolism. Haematologica. 92:812–818. 2007.PubMed/NCBI View Article : Google Scholar |
|
|
Chopard RP, Miranda Neto MH, Biazotto W and Molinari SL: Age-related changes in the human renal veins and their valves. Ital J Anat Embryol. 99:91–101. 1994.PubMed/NCBI |
|
|
Bergan JJ, Schmid-Schonbein GW, Smith PD, Nicolaides AN, Boisseau MR and Eklof B: Chronic venous disease. N Engl J Med. 355:488–498. 2006.PubMed/NCBI View Article : Google Scholar |
|
|
Mahmoodi BK, Gansevoort RT, Veeger NJ, Matthews AG, Navis G, Hillege HL and van der Meer J: Prevention of Renal and Vascular End-stage Disease (PREVEND) Study Group: Microalbuminuria and risk of venous thromboembolism. JAMA. 301:1790–1797. 2009.PubMed/NCBI View Article : Google Scholar |
|
|
Carpentier P and Priollet P: Epidemiology of chronic venous insufficiency. Presse Med. 23:197–201. 1994.(In French). PubMed/NCBI |
|
|
Miniati M, Prediletto R, Formichi B, Marini C, Di Ricco G, Tonelli L, Allescia G and Pistolesi M: Accuracy of clinical assessment in the diagnosis of pulmonary embolism. Am J Respir Crit Care Med. 159:864–871. 1999.PubMed/NCBI View Article : Google Scholar |
|
|
Pollack CV, Schreiber D, Goldhaber SZ, Slattery D, Fanikos J, O'Neil BJ, Thompson JR, Hiestand B, Briese BA, Pendleton RC, et al: Clinical characteristics, management, and outcomes of patients diagnosed with acute pulmonary embolism in the emergency department: initial report of EMPEROR (Multicenter Emergency Medicine Pulmonary Embolism in the Real World Registry). J Am Coll Cardiol. 57:700–706. 2011.PubMed/NCBI View Article : Google Scholar |
|
|
Robert-Ebadi H and Righini M: Diagnosis and management of pulmonary embolism in the elderly. Eur J Intern Med. 25:343–349. 2014.PubMed/NCBI View Article : Google Scholar |
|
|
Stein PD and Henry JW: Clinical characteristics of patients with acute pulmonary embolism stratified according to their presenting syndromes. Chest. 112:974–979. 1997.PubMed/NCBI View Article : Google Scholar |
|
|
Song Z, Wu H, Cao H, Tang M, Yang S and Qin L: Nephrotic syndrome with acute pulmonary embolism in young adults: Two case reports. Medicine (Baltimore). 97(e11495)2018.PubMed/NCBI View Article : Google Scholar |
|
|
Prandoni P, Lensing AW, Prins MH, Ciammaichella M, Perlati M, Mumoli N, Bucherini E, Visonà A, Bova C, Imberti D, et al: Prevalence of pulmonary embolism among patients hospitalized for syncope. N Engl J Med. 375:1524–1531. 2016.PubMed/NCBI View Article : Google Scholar |
|
|
Le Gal G, Righini M, Roy PM, Meyer G, Aujesky D, Perrier A and Bounameaux H: Differential value of risk factors and clinical signs for diagnosing pulmonary embolism according to age. J Thromb Haemost. 3:2457–2464. 2005.PubMed/NCBI View Article : Google Scholar |
|
|
Imberti D and Barillari G: eXperience VTE Italian Group: Real-Life Management of Venous Thromboembolism With Rivaroxaban: Results From EXperience VTE, an Italian Epidemiological Survey. Clin Appl Thromb Hemost. 24:241–247. 2018.PubMed/NCBI View Article : Google Scholar |
|
|
Prandoni P, Lensing AW, Buller HR, Carta M, Cogo A, Vigo M, Casara D, Ruol A and ten Cate JW: Comparison of subcutaneous low-molecular-weight heparin with intravenous standard heparin in proximal deep-vein thrombosis. Lancet. 339:441–445. 1992.PubMed/NCBI View Article : Google Scholar |
|
|
Columbus Investigators, Büller HR, Gent M, Gallus AS, Ginsberg J, Prins MH and Baildon R: Low-molecular-weight heparin in the treatment of patients with venous thromboembolism. N Engl J Med. 337:657–662. 1997.PubMed/NCBI View Article : Google Scholar |
|
|
Eekels JJM, Althaus K, Bakchoul T, Kroll H, Kiefel V, Nazy I, Lee LS, Sachs U, Warkentin TE and Greinacher A: An international external quality assessment for laboratory diagnosis of heparin-induced thrombocytopenia. J Thromb Haemost. 17:525–531. 2019.PubMed/NCBI View Article : Google Scholar |
|
|
Toda A, Uehara S, Inoue T, Utoh M, Kusama T, Shimizu M, Uno Y, Mogi M, Sasaki E and Yamazaki H: Effects of aging and rifampicin pretreatment on the pharmacokinetics of human cytochrome P450 probes caffeine, warfarin, omeprazole, metoprolol and midazolam in common marmosets genotyped for cytochrome P450 2C19. Xenobiotica. 48:720–726. 2018.PubMed/NCBI View Article : Google Scholar |
|
|
Prins MH, Lensing AW, Bauersachs R, van Bellen B, Bounameaux H, Brighton TA, Cohen AT, Davidson BL, Decousus H, Raskob GE, et al: 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. 11(21)2013.PubMed/NCBI View Article : Google Scholar |
|
|
Lopez-Jimenez L, Montero M, Gonzalez-Fajardo JA, Arcelus JI, Suárez C, Lobo JL and Monreal M: RIETE Investigators: Venous thromboembolism in very elderly patients: Findings from a prospective registry (RIETE). Haematologica. 91:1046–1051. 2006.PubMed/NCBI |
|
|
Lim W, Dentali F, Eikelboom JW and Crowther MA: Meta-analysis: Low-molecular-weight heparin and bleeding in patients with severe renal insufficiency. Ann Intern Med. 144:673–684. 2006.PubMed/NCBI View Article : Google Scholar |
|
|
Silverstein RL, Bauer KA, Cushman M, Esmon CT, Ershler WB and Tracy RP: Venous thrombosis in the elderly: More questions than answers. Blood. 110:3097–3101. 2007.PubMed/NCBI View Article : Google Scholar |
|
|
Limdi NA, Beasley TM, Baird MF, Goldstein JA, McGwin G, Arnett DK, Acton RT and Allon M: Kidney function influences warfarin responsiveness and hemorrhagic complications. J Am Soc Nephrol. 20:912–921. 2009.PubMed/NCBI View Article : Google Scholar |
|
|
Mangoni AA and Jackson SH: Age-related changes in pharmacokinetics and pharmacodynamics: Basic principles and practical applications. Br J Clin Pharmacol. 57:6–14. 2004.PubMed/NCBI View Article : Google Scholar |
|
|
Garcia D, Regan S, Crowther M, Hughes RA and Hylek EM: Warfarin maintenance dosing patterns in clinical practice: Implications for safer anticoagulation in the elderly population. Chest. 127:2049–2056. 2005.PubMed/NCBI View Article : Google Scholar |
|
|
Campbell NR, Hull RD, Brant R, Hogan DB, Pineo GF and Raskob GE: Aging and heparin-related bleeding. Arch Intern Med. 156:857–860. 1996.PubMed/NCBI |
|
|
Ageno W, Gallus AS, Wittkowsky A, Crowther M, Hylek EM and Palareti G: Oral anticoagulant therapy: Antithrombotic therapy and prevention of thrombosis, 9th edition: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 141 (Suppl 2):e44S–e88S. 2012.PubMed/NCBI View Article : Google Scholar |
|
|
Cook LM, Kahn SR, Goodwin J and Kovacs MJ: Frequency of renal impairment, advanced age, obesity and cancer in venous thromboembolism patients in clinical practice. J Thromb Haemost. 5:937–941. 2007.PubMed/NCBI View Article : Google Scholar |
|
|
Barba R, Marco J, Martin-Alvarez H, Rondon P, Fernández-Capitan C, Garcia-Bragado F and Monreal M: RIETE investigators: The influence of extreme body weight on clinical outcome of patients with venous thromboembolism: Findings from a prospective registry (RIETE). J Thromb Haemost. 3:856–862. 2005.PubMed/NCBI View Article : Google Scholar |
|
|
Steffel J, Verhamme P, Potpara TS, Albaladejo P, Antz M, Desteghe L, Haeusler KG, Oldgren J, Reinecke H, Roldan-Schilling V, et al: The 2018 European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation. Eur Heart J. 39:1330–1393. 2018.PubMed/NCBI View Article : Google Scholar |
|
|
Eriksson BI, Borris LC, Friedman RJ, Haas S, Huisman MV, Kakkar AK, Bandel TJ, Beckmann H, Muehlhofer E, Misselwitz F, et al: Rivaroxaban versus enoxaparin for thromboprophylaxis after hip arthroplasty. N Engl J Med. 358:2765–2775. 2008.PubMed/NCBI View Article : Google Scholar |
|
|
Eikelboom JW, Connolly SJ, Bosch J, Dagenais GR, Hart RG, Shestakovska O, Diaz R, Alings M, Lonn EM, Anand SS, et al: Rivaroxaban with or without Aspirin in Stable Cardiovascular Disease. N Engl J Med. 377:1319–1330. 2017.PubMed/NCBI View Article : Google Scholar |
|
|
Geldhof V, Vandenbriele C, Verhamme P and Vanassche T: Venous thromboembolism in the elderly: Efficacy and safety of non-VKA oral anticoagulants. Thromb J. 12(21)2014.PubMed/NCBI View Article : Google Scholar |
|
|
Greinacher A, Thiele T and Selleng K: Reversal of anticoagulants: An overview of current developments. Thromb Haemost. 113:931–942. 2015.PubMed/NCBI View Article : Google Scholar |
|
|
van Bellen B, Bamber L, Correa de Carvalho F, Prins M, Wang M and Lensing AW: Reduction in the length of stay with rivaroxaban as a single-drug regimen for the treatment of deep vein thrombosis and pulmonary embolism. Curr Med Res Opin. 30:829–837. 2014.PubMed/NCBI View Article : Google Scholar |
|
|
Lefebvre P, Coleman CI, Bookhart BK, Wang ST, Mody SH, Tran KN, Zhuo DY, Huynh L and Nutescu EA: Cost-effectiveness of rivaroxaban compared with enoxaparin plus a vitamin K antagonist for the treatment of venous thromboembolism. J Med Econ. 17:52–64. 2014.PubMed/NCBI View Article : Google Scholar |
|
|
Merli GJ, Hollander JE, Lefebvre P, Laliberté F, Raut MK, Germain G, Bookhart B and Pollack CV: Costs of hospital visits among patients with deep vein thrombosis treated with rivaroxaban and LMWH/warfarin. J Med Econ. 19:84–90. 2016.PubMed/NCBI View Article : Google Scholar |
|
|
Ho P, Brooy BL, Hayes L and Lim WK: Direct oral anticoagulants in frail older adults: A geriatric perspective. Semin Thromb Hemost. 41:389–394. 2015.PubMed/NCBI View Article : Google Scholar |
|
|
Siegal DM, Curnutte JT, Connolly SJ, Lu G, Conley PB, Wiens BL, Mathur VS, Castillo J, Bronson MD, Leeds JM, et al: Andexanet Alfa for the Reversal of Factor Xa Inhibitor Activity. N Engl J Med. 373:2413–2424. 2015.PubMed/NCBI View Article : Google Scholar |
