Mortality in Patients With Atrial Fibrillation Receiving Nonrecommended Doses of Direct Oral Anticoagulants

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY

卷:76

Article

Camm, Alan John¹  Cools, Frank²  Virdone, Saverio³  Bassand, Jean-Pierre^3,4  Fitzmaurice, David Andrew⁵  Fox, Keith Alexander Arthur⁶  Goldhaber, Samuel Zachary^7,8  Goto, Shinya⁹  Haas, Sylvia¹⁰  Mantovani, Lorenzo Giovanni^11,12  Kayani, Gloria³  Turpie, Alexander Graham Grierson¹³  Verheugt, Freek Willem Antoon¹⁴  Kakkar, Ajay Kumar^3,15 

[1] St Georges Univ London, Cardiol Clin Acad Grp, Mol & Clin Sci Res Inst, London, England

[2] AZ KLINA, Dept Cardiol, Brasschaat, Belgium

[3] Thrombosis Res Inst, Dept Clin Res, London, England

[4] Univ Besancon, Dept Cardiol, Besancon, France

[5] Univ Warwick, Warwick Med Sch, Coventry, W Midlands, England

[6] Univ Edinburgh, Ctr Cardiovasc Sci, Edinburgh, Midlothian, Scotland

[7] Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA

[8] Harvard Med Sch, Boston, MA 02115 USA

[9] Tokai Univ, Sch Med, Dept Med Cardiol, Hiratsuka, Kanagawa, Japan

[10] Tech Univ Munich, Dept Med, Munich, Germany

[11] Univ Milano Bicocca, Ctr Publ Hlth Res CESP, Postgrad Sch Hyg & Prevent Med, Milan, Italy

[12] IRCCS Multimed, Value Based Healthcare Unit, Sesto San Giovanni, Italy

[13] McMaster Univ, Dept Med, Hamilton, ON, Canada

[14] Onze Lieve Vrouwe Gasthuis OLVG, Dept Cardiol, Amsterdam, Netherlands

[15] UCL, London, England

关键词: atrial fibrillation;    direct oral anticoagulants;    dosing;    stroke prevention;   

DOI  :  10.1016/j.jacc.2020.07.045

来源: Elsevier

【 摘 要 】

BACKGROUND The recommended doses for direct oral anticoagulants (DOACs) to prevent stroke and systemic embolism (SE) in patients with atrial fibrillation (AF) are described in specific regulatory authority approvals. OBJECTIVES The impact of DOAC dosing, according to the recommended guidance on all-cause mortality, stroke/SE, and major bleeding, was assessed at 2-year follow-up in patients with newly diagnosed AF. METHODS Of a total of 34,926 patients enrolled (2013 to 2016) in the prospective GARFIELD-AF (Global Anticoagulant Registry in the FIELD-AF), 10,426 patients received a DOAC. RESULTS The majority of patients (72.9%) received recommended dosing, 23.2% were underdosed, and 3.8% were overdosed. Nonrecommended dosing (underdosage and overdosage combined) compared with recommended dosing was associated with a higher risk of all-cause mortality (hazard ratio [HR]: 1.24; 95% confidence interval [CI]: 1.04 to 1.48); HR: 1.25 (95% CI: 1.04 to 1.50) for underdosing, and HR: 1.19 (95% 0: 0.83 to 1.71) for overdosing. The excess deaths were cardiovascular including heart failure and myocardial infarction. The risks of stroke/SE and major bleeding were not significantly different irrespective of the level of dosing, although underdosed patients had a significantly tower risk of bleeding. A nonsignificant trend to higher risks of stroke/SE (HR: 1.51; 95% 0: 0.79 to 2.91) and major bleeding (HR: 1.29; 95% 0: 0.59 to 2.78) was observed in patients with overdosing. CONCLUSIONS In GARFIELD-AF, most patients received the recommended DOAC doses according to country-specific guidelines. Prescription of nonrecommended doses was associated with an increased risk of death, mostly cardiovascular death, compared with patients on recommended doses, after adjusting for baseline factors. (C) 2020 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation.

【 授权许可】

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