Novel Oral Anticoagulants for the Prevention of Stroke in Patients with Atrial Fibrillation and Hypertension: A Meta-Analysis
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Hypertension is associated with increased risk of stroke and bleeding in patients with atrial fibrillation (AF). In the present study, we aimed to investigate the influence of hypertension status in patients with AF receiving treatment with non-vitamin K antagonist oral anticoagulants (NOACs).
PubMed, Embase, and Cochrane Library were searched from the inception of each database to November 2017. Randomized controlled trials (RCTs) that evaluated NOACs versus warfarin in patients with AF and hypertension were identified. A meta-analysis was performed using random- or fixed-effects models according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
Five trials (72,967 patients, including 51,378 patients with hypertension) were enrolled. NOACs significantly reduced the risk of stroke and systemic embolism (hazard ratio [HR] 0.87, 95% confidence interval [CI] 0.81–0.94, n = 51,378 patients), hemorrhagic stroke (HR 0.55, 95% CI 0.41–0.74, n = 28,818 patients), death from any cause (HR 0.91, 95% CI 0.85–0.97, n = 43,101 patients), major bleeding (HR 0.78, 95% CI 0.74–0.83, n = 51,378 patients) and intracranial bleeding (HR 0.50, 95% CI 0.38–0.67, n = 27,185 patients). The benefits of NOACs in comparison with warfarin were consistent in AF patients with or without hypertension (Pinteraction for all outcomes > 0.05).
Our findings suggest that NOACs can be recommended for the prevention of stroke or systemic embolism in patients with AF and hypertension.
We acknowledge Dr. Robert P. Giugliano (Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA) for providing additional data and substantial support.
Compliance with Ethical Standards
No external funding was used in the preparation of this manuscript.
Conflict of interest
Yayuan Zheng, Yuyu Liu, Jihong Bi, Weiguang Lai, Chunyu Lin, Jianhong Zhu, Weimin Yao and Qiusheng Chen declare that they have no potential conflicts of interest that might be relevant to the contents of this manuscript.
This article does not contain any studies with human participants or animals performed by any of the authors.
This article does not contain any studies with human participants or animals performed by any of the authors and no informed consent was needed.
- 2.Granger CB, Alexander JH, McMurray JJ, 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 FW, Zhu J, Wallentin L, ARISTOTLE Committees Investigators. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011;365:981–92.CrossRefGoogle Scholar
- 3.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, ENGAGE AF-TIMI 48 Investigators. Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2013;369:2093–104.CrossRefGoogle Scholar
- 4.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 HC, Joyner CD, Wallentin L, RE-LY Steering Committee Investigators. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361:1139–51.CrossRefGoogle Scholar
- 5.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 KA, Califf RM, ROCKET AF Investigators. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011;365:883–91.CrossRefGoogle Scholar
- 10.Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche PC, Ioannidis JP, Clarke M, Devereaux PJ, Kleijnen J, Moher D. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ. 2009;339:b2700.CrossRefGoogle Scholar
- 13.Rao MP, Halvorsen S, Wojdyla D, Thomas L, Alexander JH, Hylek EM, Hanna M, Bahit MC, Lopes RD, De Caterina R, Erol C, Goto S, Lanas F, Lewis BS, Husted S, Gersh BJ, Wallentin L, Granger CB, Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) Steering Committee and Investigators. Blood pressure control and risk of stroke or systemic embolism in patients with atrial fibrillation: results from the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial. J Am Heart Assoc. 2015;4(12):e002015.CrossRefGoogle Scholar
- 14.Nagarakanti R, Wallentin L, Noack H, Brueckmann M, Reilly P, Clemens A, Connolly SJ, Yusuf S, Ezekowitz MD. Comparison of characteristics and outcomes of dabigatran versus warfarin in hypertensive patients with atrial fibrillation (from the RE-LY trial). Am J Cardiol. 2015;116(8):1204–9.CrossRefGoogle Scholar
- 15.Vemulapalli S, Hellkamp AS, Jones WS, Piccini JP, Mahaffey KW, Becker RC, Hankey GJ, Berkowitz SD, Nessel CC, Breithardt G, Singer DE, Fox KA, Patel MR. Blood pressure control and stroke or bleeding risk in anticoagulated patients with atrial fibrillation: results from the ROCKET AF Trial. Am Heart J. 2016;178:74–84.CrossRefGoogle Scholar
- 16.Matsumoto M, Hori M, Tanahashi N, Momomura S, Uchiyama S, Goto S, Izumi T, Koretsune Y, Kajikawa M, Kato M, Ueda H, Iekushi K, Yamanaka S, Tajiri M. Rivaroxaban versus warfarin in Japanese patients with non-valvular atrial fibrillation in relation to hypertension: a subgroup analysis of the J-ROCKET AF trial. Hypertens Res. 2014;37(5):457–62.CrossRefGoogle Scholar
- 17.Figuera M, Cinza S, Egocheaga I, Marín N, Prieto MA, SILVER BRONCE-AP investigators. Clinical characteristics and management of patients with atrial fibrillation treated with direct oral anticoagulants according to blood pressure control. Hipertens Riesgo Vasc. 2018. https://doi.org/10.1016/j.hipert.2018.01.003.Google Scholar
- 19.Diener HC, Aisenberg J, Ansell J, Atar D, Breithardt G, Eikelboom J, Ezekowitz MD, Granger CB, Halperin JL, Hohnloser SH, Hylek EM, Kirchhof P, Lane DA, Verheugt FWA, Veltkamp R, Lip GYH. Choosing a particular oral anticoagulant and dose for stroke prevention in individual patients with non-valvular atrial fibrillation: part 2. Eur Heart J. 2017;38(12):860–8.Google Scholar
- 22.Kirchhof P, Benussi S, Kotecha D, Ahlsson A, Atar D, Casadei B, Castella M, Diener HC, 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 GY, 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 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Europace. 2016;18(11):1609–78.CrossRefGoogle Scholar
- 24.Savarese G, Giugliano RP, Rosano GM, McMurray J, Magnani G, Filippatos G, Dellegrottaglie S, Lund LH, Trimarco B, Perrone-Filardi P. Efficacy and safety of novel oral anticoagulants in patients with atrial fibrillation and heart failure: a meta-analysis. JACC Heart Fail. 2016;4(11):870–80.CrossRefGoogle Scholar