Alan John Camm1, Frank Cools2, Saverio Virdone3, Jean-Pierre Bassand4, David Andrew Fitzmaurice5, Keith Alexander Arthur Fox6, Samuel Zachary Goldhaber7, Shinya Goto8, Sylvia Haas9, Lorenzo Giovanni Mantovani10, Gloria Kayani3, Alexander Graham Grierson Turpie11, Freek Willem Antoon Verheugt12, Ajay Kumar Kakkar13. 1. Cardiology Clinical Academic Group Molecular & Clinical Sciences Research Institute, St. George's University of London, London, United Kingdom. Electronic address: jcamm@sgul.ac.uk. 2. Department of Cardiology, AZ KLINA, Brasschaat, Belgium. 3. Department of Clinical Research, Thrombosis Research Institute, London, United Kingdom. 4. Department of Clinical Research, Thrombosis Research Institute, London, United Kingdom; Department of Cardiology, Besançon, Besançon, France. 5. Warwick Medical School, University of Warwick, Coventry, United Kingdom. 6. Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom. 7. Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. 8. Department of Medicine (Cardiology), Tokai University School of Medicine, Kanagawa, Japan. 9. Formerly Department of Medicine, Technical University of Munich, Munich, Germany. 10. Center for Public Health Research (CESP), PostGraduate School of Hygiene and Preventive Medicine, University of Milan Bicocca, Milan, Italy; Value-Based Healthcare Unit, IRCCS Multimedica, Sesto San Giovanni, Italy. 11. Department of Medicine, McMaster University, Hamilton, Ontario, Canada. 12. Department of Cardiology, Onze Lieve Vrouwe Gasthuis (OLVG), Amsterdam, the Netherlands. 13. Department of Clinical Research, Thrombosis Research Institute, London, United Kingdom; University College London, London, United Kingdom.
Abstract
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% CI: 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 lower risk of bleeding. A nonsignificant trend to higher risks of stroke/SE (HR: 1.51; 95% CI: 0.79 to 2.91) and major bleeding (HR: 1.29; 95% CI: 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. (Global Anticoagulant Registry in the Field-AF [GARFIELD-AF]; NCT01090362).
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% CI: 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 lower risk of bleeding. A nonsignificant trend to higher risks of stroke/SE (HR: 1.51; 95% CI: 0.79 to 2.91) and major bleeding (HR: 1.29; 95% CI: 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. (Global Anticoagulant Registry in the Field-AF [GARFIELD-AF]; NCT01090362).
Authors: Özer Badak; Ali Rıza Demir; Tugay Önal; Taylan Akgün; Osman Can Yontar; Ömer Şatıroğlu; Hakan Duman; Ertuğrul Okuyan; Mehmet Melek; İbrahim Etem Dural Journal: Int J Cardiol Heart Vasc Date: 2022-03-02
Authors: Geoffrey D Barnes; Emily Sippola; Allison Ranusch; Linda Takamine; Michael Lanham; Michael Dorsch; Anne Sales; Jeremy Sussman Journal: Implement Sci Commun Date: 2022-02-02