Abstract
Several studies have investigated the efficacy and safety outcomes of non-vitamin K antagonist oral anticoagulants (NOACs) versus warfarin in patients with atrial fibrillation (AF) and heart failure (HF). Herein, this meta-analysis was aimed to compare the effect of NOACs with warfarin in this population. We systematically searched the PubMed database until December 2019 for studies that compared the effect of NOACs with warfarin in patients with AF and HF. Risk ratios (RRs) and 95% confidence intervals (CIs) were abstracted and then pooled using a random-effects model. A total of nine studies were included in this meta-analysis. Compared with warfarin use, the use of NOACs was significantly associated with reduced risks of stroke or systemic embolism (RR = 0.82 (95% CI, 0.73–0.92)), all-cause death (RR = 0.87 (95% CI, 0.80–0.94)), major bleeding (RR = 0.84; (95% CI, 0.74–0.97)), intracranial hemorrhage (RR = 0.50; 95% CI, 0.43–0.59), and hemorrhagic stroke (RR = 0.49 (95% CI, 0.38–0.63)). There were no differences in the risks of ischemic stroke (RR = 0.89 (95% CI, 0.75–1.04)) and gastrointestinal bleeding (RR = 1.11 (95% CI, 0.79–1.55)) in patients treated with NOACs versus warfarin. Compared with warfarin use, the use of NOACs had similar or lower risks of thromboembolic and bleeding events in patients with AF and HF.
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References
January CT, Wann LS, Calkins H, Chen LY, Cigarroa JE, Cleveland JC, Ellinor PT, Ezekowitz MD, Field ME, Furie KL, Heidenreich PA, Murray KT, Shea JB, Tracy CM, Yancy CW (2019) 2019 AHA/ACC/HRS Focused Update of the 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society in Collaboration With the Society of Thoracic Surgeons. Circulation 140(2):R665
Zhu W, Xiong Q, Hong K (2015) Meta-analysis of CHADS2 versus CHA2DS2-VASc for predicting stroke and thromboembolism in atrial fibrillation patients independent of anticoagulation. Tex Heart I J 42(1):6–15
Adelborg K, Szépligeti S, Sundbøll J, Horváth-Puhó E, Henderson VW, Ording A, Pedersen L, Sørensen HT (2017) Risk of stroke in patients with heart failure. Stroke. 48(5):1161–1168
Kang SH, Kim J, Park JJ, Oh IY, Yoon CH, Kim HJ, Kim K, Choi DJ (2017) Risk of stroke in congestive heart failure with and without atrial fibrillation. Int J Cardiol 248:182–187
Giugliano RP, Ruff CT, Braunwald E, Murphy SA, Wiviott SD, Halperin JL, Waldo AL, Ezekowitz MD, Weitz JI, Špinar J, Ruzyllo W, Ruda M, Koretsune Y, Betcher J, Shi M, Grip LT, Patel SP, Patel I, Hanyok JJ, Mercuri M, Antman EM (2013) Edoxaban versus warfarin in patients with atrial fibrillation. New Engl J Med. 369(22):2093–2104
Granger CB, Alexander JH, McMurray JJV, Lopes RD, Hylek EM, Hanna M, Al-Khalidi HR, Ansell J, Atar D, Avezum A, Bahit MC, Diaz R, Easton JD, Ezekowitz JA, Flaker G, Garcia D, Geraldes M, Gersh BJ, Golitsyn S, Goto S, Hermosillo AG, Hohnloser SH, Horowitz J, Mohan P, Jansky P, Lewis BS, Lopez-Sendon JL, Pais P, Parkhomenko A, Verheugt FWA, Zhu J, Wallentin L (2011) Apixaban versus warfarin in patients with atrial fibrillation. New Engl J Med. 365(11):981–992
Patel MR, Mahaffey KW, Garg J, Pan G, Singer DE, Hacke W, Breithardt G, Halperin JL, Hankey GJ, Piccini JP, Becker RC, Nessel CC, Paolini JF, Berkowitz SD, Fox KAA, Califf RM (2011) Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. New Engl J Med. 365(10):883–891
Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, Parekh A, Pogue J, Reilly PA, Themeles E, Varrone J, Wang S, Alings M, Xavier D, Zhu J, Diaz R, Lewis BS, Darius H, Diener H, Joyner CD, Wallentin L (2009) Dabigatran versus warfarin in patients with atrial fibrillation. New Engl J Med. 361(12):1139–1151
Kirchhof P, Benussi S, Kotecha D, Ahlsson A, Atar D, Casadei B, Castella M, Diener H, Heidbuchel H, Hendriks J, Hindricks G, Manolis AS, Oldgren J, Popescu BA, Schotten U, Van Putte B, Vardas P, Agewall S, Camm J, Baron Esquivias G, Budts W, Carerj S, Casselman F, Coca A, De Caterina R, Deftereos S, Dobrev D, Ferro JM, Filippatos G, Fitzsimons D, Gorenek B, Guenoun M, Hohnloser SH, Kolh P, Lip GYH, Manolis A, McMurray J, Ponikowski P, Rosenhek R, Ruschitzka F, Savelieva I, Sharma S, Suwalski P, Tamargo JL, Taylor CJ, Van Gelder IC, Voors AA, Windecker S, Zamorano JL, Zeppenfeld K (2016) 2016 ESC guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J 37(38):2893–2962
Steffel J, Verhamme P, Potpara TS, Albaladejo P, Antz M, Desteghe L, Haeusler KG, Oldgren J, Reinecke H, Roldan-Schilling V, Rowell N, Sinnaeve P, Collins R, Camm AJ, Heidbüchel H, Lip GYH, Weitz J, Fauchier L, Lane D, Boriani G, Goette A, Keegan R, MacFadyen R, Chiang C, Joung B, Shimizu W (2018) 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(16):1330–1393
Magnani G, Giugliano RP, Ruff CT, Murphy SA, Nordio F, Metra M, Moccetti T, Mitrovic V, Shi M, Mercuri M, Antman EM, Braunwald E (2016) Efficacy and safety of edoxaban compared with warfarin in patients with atrial fibrillation and heart failure: insights from ENGAGE AF-TIMI 48. Eur J Heart Fail 18(9):1153–1161
Ferreira J, Ezekowitz MD, Connolly SJ, Brueckmann M, Fraessdorf M, Reilly PA, Yusuf S, Wallentin L (2013) Dabigatran compared with warfarin in patients with atrial fibrillation and symptomatic heart failure: a subgroup analysis of the RE-LY trial. Eur J Heart Fail 15(9):1053–1061
McMurray JJV, Ezekowitz JA, Lewis BS, Gersh BJ, van Diepen S, Amerena J, Bartunek J, Commerford P, Oh B, Harjola V, Al-Khatib SM, Hanna M, Alexander JH, Lopes RD, Wojdyla DM, Wallentin L, Granger CB (2016) Left ventricular systolic dysfunction, heart failure, and the risk of stroke and systemic embolism in patients with atrial fibrillation. Circ Heart Fail 6(3):451–460
van Diepen S, Hellkamp AS, Patel MR, Becker RC, Breithardt G, Hacke W, Halperin JL, Hankey GJ, Nessel CC, Singer DE, Berkowitz SD, Califf RM, Fox KAA, Mahaffey KW (2013) Efficacy and safety of rivaroxaban in patients with heart failure and nonvalvular atrial fibrillation. Circ Heart Fail 6(4):740–747
Savarese G, Giugliano RP, Rosano GM, McMurray J, Magnani G, Filippatos G, Dellegrottaglie S, Lund LH, Trimarco B, Perrone-Filardi P (2016) Efficacy and safety of novel oral anticoagulants in patients with atrial fibrillation and heart failure: a meta-analysis. JACC Heart Fail 4(11):870–880
Xiong Q, Lau YC, Senoo K, Lane DA, Hong K, Lip GYH (2015) Non-vitamin K antagonist oral anticoagulants (NOACs) in patients with concomitant atrial fibrillation and heart failure: a systemic review and meta-analysis of randomized trials. Eur J Heart Fail 17(11):1192–1200
Fawzy AM, Yang WY, Lip GY (2019) Safety of direct oral anticoagulants in real-world clinical practice: translating the trials to everyday clinical management. Expert Opin Drug Saf 18(3):187–209
Higgins JP, Altman DG, Gotzsche PC, Juni P, Moher D, Oxman AD, Savovic J, Schulz KF, Weeks L, Sterne JA (2011) The Cochrane collaboration’s tool for assessing risk of bias in randomised trials. BMJ. 343:d5928
Wells GA, Shea B, O’Connell D, Peterson J, Welch V, Losos M, Tugwell P (2014) The Newcastle Ottawa Scale (NOS) for assessing the quality of nonrandomized studies in meta-analyses. Available at: http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp. Accessed 29 Dec 2019
Xue Z, Zhou Y, Wu C, Lin J, Liu X, Zhu W (2015) Non-vitamin K antagonist oral anticoagulants in Asian patients with atrial fibrillation: evidences from the real-world data. Heart Fail Rev (in press)
Martinez BK, Bunz TJ, Eriksson D, Meinecke AK, Sood NA, Coleman CI (2019) Effectiveness and safety of rivaroxaban vs. warfarin in patients with non-valvular atrial fibrillation and heart failure. ESC Heart Fail 6(1):10–15
Amin A, Garcia Reeves AB, Li X, Dhamane A, Luo X, Di Fusco M, Nadkarni A, Friend K, Rosenblatt L, Mardekian J, Pan X, Yuce H, Keshishian A (2019) Effectiveness and safety of oral anticoagulants in older adults with non-valvular atrial fibrillation and heart failure. PLoS One 14(3):e213614
Yoshihisa A, Sato Y, Sato T, Suzuki S, Oikawa M, Takeishi Y (2018) Better clinical outcome with direct oral anticoagulants in hospitalized heart failure patients with atrial fibrillation. BMC Cardiovasc Disor 18(1)
Adeboyeje G, Sylwestrzak G, Barron JJ, White J, Rosenberg A, Abarca J, Crawford G, Redberg R (2017) Major bleeding risk during anticoagulation with warfarin, dabigatran, apixaban, or rivaroxaban in patients with nonvalvular atrial fibrillation. J Manag Care Spec PH 23(9):968
Friberg L, Oldgren J (2017) Efficacy and safety of non-vitamin K antagonist oral anticoagulants compared with warfarin in patients with atrial fibrillation. Open Heart 4(2):e682
Connolly SJ, Eikelboom JW, Bosch J, Dagenais G, Dyal L, Lanas F, Metsarinne K, O'Donnell M, Dans AL, Ha J, Parkhomenko AN, Avezum AA, Lonn E, Lisheng L, Torp-Pedersen C, Widimsky P, Maggioni AP, Felix C, Keltai K, Hori M, Yusoff K, Guzik TJ, Bhatt DL, Branch KRH, Cook Bruns N, Berkowitz SD, Anand SS, Varigos JD, Fox KAA, Yusuf S, Sala J, Cartasegna L, Vico M, Hominal MA, Hasbani E, Caccavo A, Zaidman C, Vogel D, Hrabar A, Schygiel PO, Cuneo C, Luquez H, Mackinnon IJ, Ahuad Guerrero RA, Costabel JP, Bartolacci IP, Montana O, Barbieri M, Gomez Vilamajo O, Garcia Duran RO, Schiavi LB, Garrido M, Ingaramo A, Bordonava AP, Pelagagge MJ, Novaretto L, Albisu Di Gennero JP, Ibanez Saggia LM, Alvarez M, Vita NA, Macin SM, Dran RD, Cardona M, Guzman L, Sarjanovich RJ, Cuadrado J, Nani S, Litvak Bruno MR, Chacon C, Maffei LE, Grinfeld D, Vensentini N, Majul CR, Luciardi HL, Gonzalez Colaso PDC, Ferre Pacora FA, Van Den Heuvel P, Verhamme P, Ector B, Debonnaire P, Van De Borne P, Leroy J, Schroe H, Vranckx P, Elegeert I, Hoffer E, Dujardin K, Indio DO, Brasil C, Precoma D, Abrantes JA, Manenti E, Reis G, Saraiva J, Maia L, Hernandes M, Rossi P, Rossi Dos Santos F, Zimmermann SL, Rech R, Abib E Jr, Leaes P, Botelho R, Dutra O, Souza W, Braile M, Izukawa N, Nicolau JC, Tanajura LF, Serrano Junior CV, Minelli C, Nasi LA, Oliveira L, De Carvalho Cantarelli MJ, Tytus R, Pandey S, Lonn E, Cha J, Vizel S, Babapulle M, Lamy A, Saunders K, Berlingieri J, Kiaii B, Bhargava R, Mehta P, Hill L, Fell D, Lam A, Al-Qoofi F, Brown C, Petrella R, Ricci JA, Glanz A, Noiseux N, Bainey K, Merali F, Heffernan M, Della Siega A, Dagenais GR, Dagenais F, Brulotte S, Nguyen M, Hartleib M, Guzman R, Bourgeois R, Rupka D, Khaykin Y, Gosselin G, Huynh T, Pilon C, Campeau J, Pichette F, Diaz A, Johnston J, Shukle P, Hirsch G, Rheault P, Czarnecki W, Roy A, Nawaz S, Fremes S, Shukla D, Jano G, Cobos JL, Corbalan R, Medina M, Nahuelpan L, Raffo C, Perez L, Potthoff S, Stockins B, Sepulveda P, Pincetti C, Vejar M, Tian H, Wu X, Ke Y, Jia K, Yin P, Wang Z, Yu L, Wu S, Wu Z, Liu SW, Bai XJ, Zheng Y, Yang P, Yang YM, Zhang J, Ge J, Chen XP, Li J, Hu TH, Zhang R, Zheng Z, Chen X, Tao L, Li J, Huang W, Fu G, Li C, Dong Y, Wang C, Zhou X, Kong YE, Sotomayor A, Accini Mendoza JL, Castillo H, Urina M, Aroca G, Perez M, Molina De Salazar DI, Sanchez Vallejo G, Fernando MJ, Garcia H, Garcia LH, Arcos E, Gomez J, Cuervo Millan F, Trujillo Dada FA, Vesga B, Moreno Silgado GA, Zidkova E, Lubanda J, Kaletova M, Kryza R, Marcinek G, Richter M, Spinar J, Matuska J, Tesak M, Motovska Z, Branny M, Maly J, Maly M, Wiendl M, Foltynova Caisova L, Slaby J, Vojtisek P, Pirk J, Spinarova L, Benesova M, Canadyova J, Homza M, Florian J, Polasek R, Coufal Z, Skalnikova V, Brat R, Brtko M, Jansky P, Lindner J, Marcian P, Straka Z, Tretina M, Duarte YC, Pow Chon Long F, Sanchez M, Lopez J, Perugachi C, Marmol R, Trujillo F, Teran P, Tuomilehto J, Tuomilehto H, Tuominen M, Tuomilehto H, Kantola I, Steg G, Aboyans V, Leclercq F, Ferrari E, Boccara F, Messas E, Mismetti P, Sevestre MA, Cayla G, Motreff P, Stoerk S, Duengen H, Stellbrink C, Guerocak O, Kadel C, Braun-Dullaeus R, Jeserich M, Opitz C, Voehringer H, Appel K, Winkelmann B, Dorsel T, Nikol S, Darius H, Ranft J, Schellong S, Jungmair W, Davierwala P, Vorpahl M, Bajnok L, Laszlo Z, Noori E, Veress G, Vertes A, Zsary A, Kis E, Koranyi L, Bakai J, Boda Z, Poor F, Jarai Z, Kemeny V, Barton J, Mcadam B, Murphy A, Crean P, Mahon N, Curtin R, Macneill B, Dinneen S, Halabi M, Zimlichman R, Zeltser D, Turgeman Y, Klainman E, Lewis B, Katz A, Atar S, Zimlichman R, Nikolsky E, Bosi S, Naldi M, Faggiano P, Robba D, Mos L, Sinagra G, Cosmi F, Oltrona Visconti L, Carmine DM, Di Pasquale G, Di Biase M, Mandorla S, Bernardinangeli M, Piccinni GC, Gulizia MM, Galvani M, Venturi F, Morocutti G, Baldin MG, Olivieri C, Perna GP, Cirrincione V, Kanno T, Daida H, Ozaki Y, Miyamoto N, Higashiue S, Domae H, Hosokawa S, Kobayashi H, Kuramochi T, Fujii K, Mizutomi K, Saku K, Kimura K, Higuchi Y, Abe M, Okuda H, Noda T, Mita T, Hirayama A, Onaka H, Inoko M, Hirokami M, Okubo M, Akatsuka Y, Imamaki M, Kamiya H, Manita M, Himi T, Ueno H, Hisamatsu Y, Ako J, Nishino Y, Kawakami H, Yamada Y, Koretsune Y, Yamada T, Yoshida T, Shimomura H, Kinoshita N, Takahashi A, Yusoff K, Wan Ahmad WA, Abu Hassan MR, Kasim S, Abdul Rahim AA, Mohd Zamrin D, Machida M, Higashino Y, Utsu N, Nakano A, Nakamura S, Hashimoto T, Ando K, Sakamoto T, Prins FJ, Lok D, Milhous JG, Viergever E, Willems F, Swart H, Alings M, Breedveld R, De Vries K, Van Der Borgh R, Oei F, Zoet-Nugteren S, Kragten H, Herrman JP, Van Bergen P, Gosselink M, Hoekstra E, Zegers E, Ronner E, Den Hartog F, Bartels G, Nierop P, Van Der Zwaan C, Van Eck J, Van Gorselen E, Groenemeijer B, Hoogslag P, De Groot MR, Loyola A, Sulit DJ, Rey N, Abola MT, Morales D, Palomares E, Abat ME, Rogelio G, Chua P, Del Pilar JC, Alcaraz JD, Ebo G, Tirador L, Cruz J, Anonuevo J, Pitargue A, Janion M, Guzik T, Gajos G, Zabowka M, Rynkiewicz A, Broncel M, Szuba A, Czarnecka D, Maga P, Strazhesko I, Vasyuk Y, Sizova Z, Pozdnyakov Y, Barbarash O, Voevoda M, Poponina T, Repin A, Osipova I, Efremushkina A, Novikova N, Averkov O, Zateyshchikov D, Vertkin A, Ausheva A, Commerford P, Seedat S, Van Zyl L, Engelbrecht J, Makotoko EM, Pretorius CE, Mohamed Z, Horak A, Mabin T, Klug E, Bae J, Kim C, Kim C, Kim D, Kim YJ, Joo S, Ha J, Park CS, Kim JY, Kim Y, Jarnert C, Mooe T, Dellborg M, Torstensson I, Albertsson P, Johansson L, Al-Khalili F, Almroth H, Andersson T, Pantev E, Tengmark B, Liu BO, Rasmanis G, Wahlgren C, Moccetti T, Parkhomenko A, Tseluyko V, Volkov V, Koval O, Kononenko L, Prokhorov O, Vdovychenko V, Bazylevych A, Rudenko L, Vizir V, Karpenko O, Malynovsky Y, Koval V, Storozhuk B, Cotton J, Venkataraman A, Moriarty A, Connolly D, Davey P, Senior R, Birdi I, Calvert J, Donnelly P, Trevelyan J, Carter J, Peace A, Austin D, Kukreja N, Hilton T, Srivastava S, Walsh R, Fields R, Hakas J, Portnay E, Gogia H, Salacata A, Hunter JJ, Bacharach JM, Shammas N, Suresh D, Schneider R, Gurbel P, Banerjee S, Grena P, Bedwell N, Sloan S, Lupovitch S, Soni A, Gibson K, Sangrigoli R, Mehta R, I-Hsuan Tsai P, Gillespie E, Dempsey S, Hamroff G, Black R, Lader E, Kostis JB, Bittner V, Mcguinn W, Branch K, Malhotra V, Michaelson S, Vacante M, Mccormick M, Arimie R, Camp A, Dagher G, Koshy NM, Thew S, Costello F, Heiman M, Chilton R, Moran M, Adler F, Comerota A, Seiwert A, French W, Serota H, Harrison R, Bakaeen F, Omer S, Chandra L, Whelan A, Boyle A, Roberts-Thomson P, Rogers J, Carroll P, Colquhoun D, Shaw J, Blombery P, Amerena J, Hii C, Royse A, Singh B, Selvanayagam J, Jansen S, Lo W, Hammett C, Poulter R, Narasimhan S, Wiggers H, Nielsen H, Gislason G, Kober L, Houlind K, Boenelykke Soerensen V, Dixen U, Refsgaard J, Zeuthen E, Soegaard P, Hranai M, Gaspar L, Pella D, Hatalova K, Drozdakova E, Coman I, Dimulescu D, Vinereanu D, Cinteza M, Sinescu C, Arsenescu C, Benedek I, Bobescu E, Dobreanu D, Gaita D, Iancu A, Iliesiu A, Lighezan D, Petrescu L, Pirvu O, Teodorescu I, Tesloianu D, Vintila MM, Chioncel O (2018) Rivaroxaban with or without aspirin in patients with stable coronary artery disease: an international, randomised, double-blind, placebo-controlled trial. Lancet 391(10117):205–218
Zannad F, Anker SD, Byra WM, Cleland JGF, Fu M, Gheorghiade M, Lam CSP, Mehra MR, Neaton JD, Nessel CC, Spiro TE, van Veldhuisen DJ, Greenberg B (2018) Rivaroxaban in patients with heart failure, sinus rhythm, and coronary disease. New Engl J Med 379(14):1332–1342
Ntaios G, Vemmos K, Lip GY (2019) Oral anticoagulation versus antiplatelet or placebo for stroke prevention in patients with heart failure and sinus rhythm: Systematic review and meta-analysis of randomized controlled trials. Int J Stroke:32384623
Chung S, Kim T, Uhm J, Cha M, Lee J, Park J, Park J, Kang K, Kim J, Park HW, Choi E, Kim J, Kim C, Lee YS, Shim J, Joung B (2019) Stroke and systemic embolism and other adverse outcomes of heart failure with preserved and reduced ejection fraction in patients with atrial fibrillation (from the comparison study of drugs for symptom control and complication prevention of atrial fibrillation [CODE-AF]). Am J Cardiol (in press)
Schrutka L, Seirer B, Duca F, Binder C, Dalos D, Kammerlander A, Aschauer S, Koller L, Benazzo A, Agibetov A, Gwechenberger M, Hengstenberg C, Mascherbauer J, Bonderman D (2019) Patients with heart failure and preserved ejection fraction are at risk of gastrointestinal bleeding. J Clin Med 8(8):1240
Melgaard L, Gorst-Rasmussen A, Lane DA, Rasmussen LH, Larsen TB, Lip GY (2015) Assessment of the CHA2DS2-VASc score in predicting ischemic stroke, thromboembolism, and death in patients with heart failure with and without atrial fibrillation. JAMA. 314(10):1030–1038
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Under the directions of Jian Hu and Jianyong Ma, Faxiu Chen, Yunguo Zhou, Qin Wan, and Peng Yu contributed to the whole process of this meta-analysis including study design, literature search, data curation, methodology, data analysis, data interpretation, and draft writing. Jian Hu and Jianyong Ma revised the original draft.
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Chen, F., Zhou, Y., Wan, Q. et al. Effect of non-vitamin K antagonist oral anticoagulants versus warfarin in heart failure patients with atrial fibrillation. Heart Fail Rev 26, 1391–1397 (2021). https://doi.org/10.1007/s10741-020-09946-8
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DOI: https://doi.org/10.1007/s10741-020-09946-8