Glycemic status and risks of thromboembolism and major bleeding in patients with atrial fibrillation

Figures

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  Fig. 1. The flowchart of the enrollment of study patients. From June 1, 2001, to May 31, 2018, 2944, 5065, 6516, 7336, 3908, 3903, and 4314 AF patients with HbA1c levels of < 5.4%, 5.4%–5.6%, 5.7%–5.9%, 6.0%–6.4%, 6.5%–6.9%, 7.0%–7.9%, and \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\ge$$\end{document}≥ 8.0%, respectively, were enrolled in the present study. AF = atrial fibrillation; HbA1c = glycated hemoglobin A1c

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  Fig. 2. Cumulative incidence curves of IS/SE (a) and major bleeding (b) among AF patients in different HbA1c categories. Thromboembolic events appeared to be higher in patients with higher HbA1c levels of 6.5%–6.9%, 7.0%–7.9%, and \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\ge$$\end{document}≥ 8.0% than in the other groups (log-rank P < 0.0001), while the risk of major bleeding was comparable across all groups (log-rank P = 0.0926). AF = atrial fibrillation; HbA1c = glycated hemoglobin A1c; IS/SE = ischemic stroke/systemic embolism

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  Fig. 3. Risks of IS/SE and major bleeding for AF patients in different HbA1c categories. Compared with patients with an HbAc1 level of < 5.4%, the risk of IS/SE significantly increased when HbA1c level was higher than 6.5%, while the risk of IS/SE was similar for patients with HbA1c levels of 5.4%–5.6%, 5.7%–5.9%, and 6.0%–6.4%. In contrast to the risk of IS/SE, the risk of major bleeding was comparable across all HbA1c categories. *Risk of IS/SE was adjusted for CHA2DS2-VASc score, use of insulin or OHAs, use of warfarin or DOACs, and eGFR. †Risk of major bleeding was adjusted for HAS-BLED score, use of insulin or OHAs, use of warfarin or DOACs, and eGFR. AF = atrial fibrillation; CI = confidence interval; DOAC = direct oral anticoagulant; eGFR = estimated glomerular filtration rate; HbA1c = glycated hemoglobin A1c; aHR = adjusted hazard ratio; IS/SE = ischemic stroke or systemic embolism; OHA = oral hypoglycemic agent

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  Fig. 4. Risks of IS/SE and major bleeding in AF patients known to have DM or with unknown DM status across different HbA1c categories. There was no interaction observed with known DM or unknown DM status regarding the risk of IS/SE compared with patients with an HbA1c of < 5.4% in each HbA1c category (P interaction > 0.05 in all categories). There was also a significant trend for an increased risk of IS/SE among patients having HbA1c of 6.5%–6.9%, 7.0%–7.9%, and \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\ge$$\end{document}≥ 8.0% for patients known to have DM or with unknown DM status (for trends, both P < 0.0001). There was no significant difference in the risk of major bleeding across all HbA1c categories in AF patients known to have DM or with unknown DM status. *Risk of IS/SE was adjusted for CHA2DS2-VASc score, use of warfarin or DOACs, and eGFR. †Risk of major bleeding was adjusted for HAS-BLED score, use of warfarin or DOACs, and eGFR. AF atrial fibrillation, aHR adjusted hazard ratio, CI…

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  Fig. 5. Risk of IS/SE for AF patients with/without taking OACs across different HbA1c categories. Results about the analysis of risk of IS/SE were generally consistent with the main analysis when we focused on AF patients not taking OACs (n = 24,931). However, for 9105 patients receiving OACs (3966 with DOACs and 5139 with warfarin), the risk of IS/SE was not higher among patients with a higher HbA1c level than in those with HbA1c of < 5.4%. *Risk of IS/SE was adjusted for CHA2DS2-VASc score, use of insulin or OHAs, and eGFR. AF atrial fibrillation, aHR adjusted hazard ratio, CI confidence interval, DOAC direct oral anticoagulant, eGFR estimated glomerular filtration rate, HbA1c glycated hemoglobin A1c, IS/SE ischemic stroke/systemic embolism, OAC oral anticoagulant

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  Fig. 6. DOACs versus warfarin in AF patients with different HbA1c categories. Overall, DOACs were associated with a lower risk of IS/SE (adjusted HR 0.61, 95% CI 0.49–0.75, P < 0.0001) and major bleeding (adjusted HR 0.30, 95% CI 0.21–0.42, P < 0.0001) without interactions across different HbA1c categories (P interaction > 0.05 for both endpoints). *Risk of IS/SE was adjusted for CHA2DS2-VASc score, use of insulin or OHAs, and eGFR. †Risk of major bleeding was adjusted for HAS-BLED score, use of insulin or OHAs, and eGFR. AF atrial fibrillation, aHR adjusted hazard ratio, CI confidence interval, DOAC direct oral anticoagulant, eGFR estimated glomerular filtration rate, HbA1c glycated hemoglobin A1c, IS/SE ischemic stroke/systemic embolism