Phân tích rủi ro của các thuốc chống đông đường uống mới cho chảy máu tiêu hóa và xuất huyết nội sọ ở bệnh nhân rung nhĩ: một tổng quan hệ thống và phân tích meta mạng

Journal of Zhejiang University-SCIENCE B - Tập 18 - Trang 567-576 - 2017
Wei-wei Xu1, Shen-jiang Hu1, Tao Wu1
1Department of Cardiology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China

Tóm tắt

Liệu pháp chống đông bằng các thuốc chống đông đường uống mới (NOACs) ở bệnh nhân rung nhĩ (AF) đã cho thấy có tỷ lệ rủi ro-lợi ích tích cực. Tuy nhiên, đã có sự tranh cãi về các rủi ro của chảy máu tiêu hóa (GIB) và xuất huyết nội sọ (ICH), vì vậy chúng tôi đã tiến hành một tổng quan hệ thống và phân tích meta mạng sử dụng suy diễn Bayesian để phân tích các rủi ro của GIB và ICH ở những bệnh nhân AF sử dụng NOACs. Chúng tôi đã phân tích dữ liệu từ 20 thử nghiệm lâm sàng ngẫu nhiên với 91.671 bệnh nhân AF nhận thuốc chống đông, thuốc chống tiểu cầu hoặc giả dược. Phân tích meta mạng Bayesian của hai mạng lưới bằng chứng khác nhau được thực hiện sử dụng mô hình xác suất nhị thức, dựa trên một mạng lưới mà trong đó các tác nhân khác nhau (và liều lượng) được coi là các nút riêng biệt. Tỷ lệ odds (OR) và khoảng tin cậy 95% (CI) được mô hình hóa bằng phương pháp chuỗi Markov Monte Carlo. Các so sánh gián tiếp với mô hình Bayesian xác nhận rằng aspirin + clopidogrel làm tăng đáng kể rủi ro GIB ở bệnh nhân AF so với giả dược (OR 0.33, 95% CI 0.01–0.92). Warfarin được xác định là làm gia tăng đáng kể rủi ro ICH so với edoxaban 30 mg (OR 3.42, 95% CI 1.22–7.24) và dabigatran 110 mg (OR 3.56, 95% CI 1.10–8.45). Chúng tôi cũng đã xếp hạng các NOACs theo rủi ro thấp nhất của GIB (apixaban 5 mg) và ICH (apixaban 5 mg, dabigatran 110 mg và edoxaban 30 mg). Phân tích meta mạng Bayesian về điều trị bệnh nhân AF không có van với thuốc chống đông cho thấy rằng các NOACs không làm tăng rủi ro GIB và/ hoặc ICH, so với nhau.

Từ khóa

#Thuốc chống đông đường uống mới #rung nhĩ #chảy máu tiêu hóa #xuất huyết nội sọ #phân tích meta #suy diễn Bayesian

Tài liệu tham khảo

Alexander, J.H., Lopes, R.D., James, S., et al., 2011. Apixaban with antiplatelet therapy after acute coronary syndrome. N. Engl. J. Med., 365(8): 699–708. http://dx.doi.org/10.1056/NEJMoa1105819 Begg, C.B., Mazumdar, M., 1994. Operating characteristics of a rank correlation test for publication bias. Biometrics, 50(4): 1088–1101. http://dx.doi.org/10.2307/2533446 Biondi-Zoccai, G., Malavasi, V., D'Ascenzo, F., et al., 2013. Comparative effectiveness of novel oral anticoagulants for atrial fibrillation: evidence from pair-wise and warfarin controlled network meta-analyses. HSR Proc. Intens. Care Cardiovasc. Anesth., 5(1): 40–54. Camm, A.J., Lip, G.Y., de Caterina, R., et al., 2012. 2012 focused update of the ESC Guidelines for the management of atrial fibrillation: an update of the 2010 ESC Guidelines for the management of atrial fibrillation. Developed with the special contribution of the European Heart Rhythm Association. Eur. Heart J., 33(21): 2719–2747. http://dx.doi.org/10.1093/eurheartj/ehs253 Candel, F.J., Matesanz, M., Cogolludo, F., et al., 2004. Prevalence of atrial fibrillation and relationed factors in a population in the centre Madrid. An. Med. Interna (Madrid), 21(10): 477–482. https://doi.org/10.4321/S0212-71992004001000003 Chatterjee, S., Sardar, P., Biondi-Zoccai, G., et al., 2013. New oral anticoagulants and the risk of intracranial hemorrhage: traditional and Bayesian meta-analysis and mixed treatment comparison of randomized trials of new oral anticoagulants in atrial fibrillation. JAMA Neurol., 70(12): 1486–1490. http://dx.doi.org/10.1001/jamaneurol.2013.4021 Chen, W.C., Chen, Y.H., Hsu, P.I., et al., 2014. Gastrointestinal hemorrhage in warfarin anticoagulated patients: incidence, risk factor, management, and outcome. Bio-Med Res. Int., 2014:463767. http://dx.doi.org/10.1155/2014/463767 Chung, N., Jeon, H.K., Lien, L.M., et al., 2011. Safety of edoxaban, an oral factor Xa inhibitor, in Asian patients with non-valvular atrial fibrillation. Thromb. Haemost., 105(3): 535–544. http://dx.doi.org/10.1160/TH10-07-0451 Connolly, S.J., Pogue, J., Hart, R., et al., 2006. Clopidogrel plus aspirin versus oral anticoagulation for atrial fibrillation in the Atrial fibrillation Clopidogrel Trial with Irbesartan for prevention of Vascular Events (ACTIVE W): a randomised controlled trial. Lancet, 367(9526): 1903–1912. http://dx.doi.org/10.1016/S0140-6736(06)68845-4 Connolly, S.J., Laupacis, A., Gent, M., et al., 1991. Canadian atrial fibrillation anticoagulation (CAFA) Study. J. Am. Coll. Cardiol., 18(2): 349–355. http://dx.doi.org/10.1016/0735-1097(91)90585-W Connolly, S.J., Pogue, J., Hart, R.G., et al., 2009a. Effect of clopidogrel added to aspirin in patients with atrial fibrillation. N. Engl. J. Med., 360(20): 2066–2078. http://dx.doi.org/10.1056/NEJMoa0901301 Connolly, S.J., Ezekowitz, M.D., Yusuf, S., et al., 2009b. Dabigatran versus warfarin in patients with atrial fibrillation. N. Engl. J. Med., 361(12): 1139–1151. http://dx.doi.org/10.1056/NEJMoa0905561 Connolly, S.J., Eikelboom, J., Joyner, C., et al., 2011. Apixaban in patients with atrial fibrillation. N. Engl. J. Med., 364(9): 806–817. http://dx.doi.org/10.1056/NEJMoa1007432 Dias, S., Welton, N.J., Sutton, A.J., 2011. NICE DSU technical support document 2: a generalised linear modelling framework for pairwise and network meta-analysis of randomised controlled trials. Technical Support Document in Evidence Synthesis, No. TSD2. National Institute for Health and Clinical Excellence. http://core.ac.uk/download/pdf/29025987.pdf Dias, S., Welton, N.J., Sutton, A.J., et al., 2013. Evidence synthesis for decision making 4: inconsistency in networks of evidence based on randomized controlled trials. Med. Decis. Making, 33(5): 641–656. http://dx.doi.org/10.1177/0272989X12455847 Dogliotti, A., Paolasso, E., Giugliano, R.P., 2014. Current and new oral antithrombotics in non-valvular atrial fibrillation: a network meta-analysis of 79 808 patients. Heart, 100(5): 396–405. http://dx.doi.org/10.1136/heartjnl-2013-304347 Dulli, D.A., Stanko, H., Levine, R.L., 2003. Atrial fibrillation is associated with severe acute ischemic stroke. Neuroepidemiology, 22(2): 118–123. http://dx.doi.org/10.1159/000068743 Ezekowitz, M.D., Bridgers, S.L., James, K.E., et al., 1992. Warfarin in the prevention of stroke associated with nonrheumatic atrial fibrillation. Veterans Affairs Stroke Prevention in Nonrheumatic Atrial Fibrillation Investigators. N. Engl. J. Med., 327(20): 1406–1412. http://dx.doi.org/10.1056/NEJM199211123272002 Fuster, V., Ryden, L.E., Cannom, D.S., et al., 2006. ACC/ AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation. Circulation, 114(7): e257-e354. http://dx.doi.org/10.1161/circulationaha.106.177292 Gersh, B.J., Tsang, T.S., Seward, J.B., 2004. The changing epidemiology and natural history of nonvalvular atrial fibrillation: clinical implications. Trans. Am. Clin. Climatol. Assoc., 115:149–159. Gibson, C.M., Mega, J.L., Burton, P., et al., 2011. Rationale and design of the Anti-Xa therapy to lower cardiovascular events in addition to standard therapy in subjects with acute coronary syndrome-thrombolysis in myocardial infarction 51 (ATLAS-ACS 2 TIMI 51) trial: a randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of rivaroxaban in subjects with acute coronary syndrome. Am. Heart J., 161(5): 815–821.e6. http://dx.doi.org/10.1016/j.ahj.2011.01.026 Giorda, C.B., Nada, E., Tartaglino, B., 2014. Pharmacokinetics, safety, and efficacy of DPP-4 inhibitors and GLP-1 receptor agonists in patients with type 2 diabetes mellitus and renal or hepatic impairment. A systematic review of the literature. Endocrine, 46(3): 406–419. http://dx.doi.org/10.1007/s12020-014-0179-0 Giugliano, R.P., Ruff, C.T., Braunwald, E., et al., 2013. Edoxaban versus warfarin in patients with atrial fibrillation. N. Engl. J. Med., 369(22): 2093–2104. http://dx.doi.org/10.1056/NEJMoa1310907 Gomez-Outes, A., Terleira-Fernandez, A.I., Calvo-Rojas, G., et al., 2013. Dabigatran, rivaroxaban, or apixaban versus warfarin in patients with nonvalvular atrial fibrillation: a systematic review and meta-analysis of subgroups. Thrombosis, 2013:640723. http://dx.doi.org/10.1155/2013/640723 Granger, C.B., Alexander, J.H., McMurray, J.J., et al., 2011. Apixaban versus warfarin in patients with atrial fibrillation. N. Engl. J. Med., 365(11): 981–992. http://dx.doi.org/10.1056/NEJMoa1107039 Gullov, A.L., Koefoed, B.G., Petersen, P., et al., 1998. Fixed minidose warfarin and aspirin alone and in combination vs adjusted-dose warfarin for stroke prevention in atrial fibrillation: Second Copenhagen Atrial Fibrillation, Aspirin, and Anticoagulation Study. Arch. Intern. Med., 158(14): 1513–1521. http://dx.doi.org/10.1001/archinte.158.14.1513 Hellemons, B.S., Langenberg, M., Lodder, J., et al., 1999. Primary prevention of arterial thromboembolism in nonrheumatic atrial fibrillation in primary care: randomised controlled trial comparing two intensities of coumarin with aspirin. BMJ, 319(7215): 958–964. http://dx.doi.org/10.1136/bmj.319.7215.958 Higgins, J., Green, S., 2006. Cochrane Handbook for Systematic Reviews of Interventions. John Wiley & Sons, Ltd., Chichester, UK. Holster, I.L., Valkhoff, V.E., Kuipers, E.J., et al., 2013. New oral anticoagulants increase risk for gastrointestinal bleeding: a systematic review and meta-analysis. Gastroenterology, 145(1): 105–112.e15. http://dx.doi.org/10.1053/j.gastro.2013.02.041 Hori, M., Matsumoto, M., Tanahashi, N., et al., 2012. Rivaroxaban vs.warfarin in Japanese patients with atrial fibrillation. Circ. J., 76(9): 2104–2111. http://dx.doi.org/10.1253/circj.CJ-12-0454 Hu, D.Y., Zhang, H.P., Sun, Y.H., et al., 2006. The randomized study of efficiency and safety of antithrombotic therapy in nonvalvular atrial fibrillation: warfarin compared with aspirin. Chin. J. Cardiol., 34(4): 295–298 (in Chinese). Jansen, J.P., Naci, H., 2013. Is network meta-analysis as valid as standard pairwise meta-analysis? It all depends on the distribution of effect modifiers. BMC Med., 11:159. http://dx.doi.org/10.1186/1741-7015-11-159 January, C.T., Wann, L.S., Alpert, J.S., et al., 2014. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: executive summary. Circulation, 130(23): 2071–2104. http://dx.doi.org/10.1161/CIR.0000000000000040 Levi, M., Eerenberg, E., Kamphuisen, P.W., 2011. Bleeding risk and reversal strategies for old and new anticoagulants and antiplatelet agents. J. Thromb. Haemost., 9(9): 1705–1712. http://dx.doi.org/10.1111/j.1538-7836.2011.04432.x Luengo-Fernandez, R., Gray, A.M., Rothwell, P.M., 2006. Population-based study of determinants of initial secondary care costs of acute stroke in the United Kingdom. Stroke, 37(10): 2579–2587. http://dx.doi.org/10.1161/01.STR.0000240508.28625.2c Lumley, T., 2002. Network meta-analysis for indirect treatment comparisons. Stat. Med., 21(16): 2313–2324. http://dx.doi.org/10.1002/sim.1201 Mant, J., Hobbs, F.D., Fletcher, K., et al., 2007. Warfarin versus aspirin for stroke prevention in an elderly community population with atrial fibrillation (the Birmingham Atrial Fibrillation Treatment of the Aged Study, BAFTA): a randomised controlled trial. Lancet, 370(9586): 493–503. http://dx.doi.org/10.1016/S0140-6736(07)61233-1 Mega, J.L., Braunwald, E., Wiviott, S.D., et al., 2012. Rivaroxaban in patients with a recent acute coronary syndrome. N. Engl. J. Med., 366(1): 9–19. http://dx.doi.org/10.1056/NEJMoa1112277 Ogawa, S., Shinohara, Y., Kanmuri, K., 2011. Safety and efficacy of the oral direct factor Xa inhibitor apixaban in Japanese patients with non-valvular atrial fibrillation. Circ. J., 75(8): 1852–1859. http://dx.doi.org/10.1253/circj.CJ-10-1183 Patel, M.R., Mahaffey, K.W., Garg, J., et al., 2011. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N. Engl. J. Med., 365(10): 883–891. http://dx.doi.org/10.1056/NEJMoa1009638 Petersen, P., Boysen, G., Godtfredsen, J., et al., 1989. Placebocontrolled, randomised trial of warfarin and aspirin for prevention of thromboembolic complications in chronic atrial fibrillation: the Copenhagen AFASAK Study. Lancet, 333(8631): 175–179. http://dx.doi.org/10.1016/S0140-6736(89)91200-2 Ruff, C.T., Giugliano, R.P., Braunwald, E., et al., 2014. Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials. Lancet, 383(9921): 955–962. http://dx.doi.org/10.1016/S0140-6736(13)62343-0 Sacco, R.L., Adams, R., Albers, G., et al., 2006. Guidelines for prevention of stroke in patients with ischemic stroke or transient ischemic attack. Stroke, 37(2): 577–617. http://dx.doi.org/10.1161/01.STR.0000199147.30016.74 Sato, H., Ishikawa, K., Kitabatake, A., et al., 2006. Low-dose aspirin for prevention of stroke in low-risk patients with atrial fibrillation: Japan Atrial Fibrillation Stroke Trial. Stroke, 37(2): 447–451. http://dx.doi.org/10.1161/01.STR.0000198839.61112.ee Slot, K.B., Berge, E., Dorman, P., et al., 2008. Impact of functional status at six months on long term survival in patients with ischaemic stroke: prospective cohort studies. BMJ, 336(7640): 376–379. http://dx.doi.org/10.1136/bmj.39456.688333.BE Spiegelhalter, D., Thomas, A., Best, N., 2004. WinBUGS User Manual. MRC Biostatistics Unit, Cambridge. Sweeting, M.J., Sutton, A.J., Lambert, P.C., 2004. What to add to nothing? Use and avoidance of continuity corrections in meta-analysis of sparse data. Stat. Med., 23(9): 1351–1375. http://dx.doi.org/10.1002/sim.1761 The Boston Area Anticoagulation Trial for Atrial Fibrillation Investigators, 1990. The effect of low-dose warfarin on the risk of stroke in patients with nonrheumatic atrial fibrillation. N. Engl. J. Med., 323(22): 1505–1511. http://dx.doi.org/10.1056/NEJM199011293232201 Yamashita, T., Koretsune, Y., Yasaka, M., et al., 2012. Randomized, multicenter, warfarin-controlled phase IIstudy of edoxaban in Japanese patients with non-valvular atrial fibrillation. Circ. J., 76(8): 1840–1847. http://dx.doi.org/10.1253/circj.CJ-11-1140 Zhang, S., 2012. Clinical considerations of anticoagulation therapy for patients with atrial fibrillation. J. Zhejiang Univ.-Sci. B (Biomed. & Biotechnol.), 13(4): 609–615. http://dx.doi.org/10.1631/jzus.B1201007