Early Rhythm Control and the Risks of Ischemic Stroke, Heart Failure, Mortality, and Adverse Events When Performed Early (<3 Months): A Nationwide Cohort Study of Newly Diagnosed Patients with Atrial Fibrillation

Tze-Fan Chao; Yi-Hsin Chan; Chern-En Chiang; Ta-Chuan Tuan; Jo-Nan Liao; Tzeng-Ji Chen; Gregory Y. H. Lip; Shih-Ann Chen

doi:10.1055/a-1807-0336

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2022; 122(11): 1899-1910
DOI: 10.1055/a-1807-0336

Stroke, Systemic or Venous Thromboembolism

Early Rhythm Control and the Risks of Ischemic Stroke, Heart Failure, Mortality, and Adverse Events When Performed Early (<3 Months): A Nationwide Cohort Study of Newly Diagnosed Patients with Atrial Fibrillation

Authors

Tze-Fan Chao^*

¹Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

²Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan

³Cardiovascular Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan
Yi-Hsin Chan^*

⁴The Cardiovascular Department, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan

⁵College of Medicine, Chang Gung University, Taoyuan, Taiwan

⁶Microscopy Core Laboratory, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan
Chern-En Chiang

¹Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

²Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan

³Cardiovascular Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan

⁷General Clinical Research Center, Taipei Veterans General Hospital, Taipei, Taiwan
Ta-Chuan Tuan

¹Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

²Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan

³Cardiovascular Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan
Jo-Nan Liao

¹Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

²Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan

³Cardiovascular Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan
Tzeng-Ji Chen

⁸Department of Family Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
Gregory Y. H. Lip ^*^**

⁹Liverpool Centre for Cardiovascular Science, University of Liverpool & Liverpool Heart and Chest Hospital, Liverpool, United Kingdom

¹⁰Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Aalborg University, Aalborg, Denmark, United Kingdom
Shih-Ann Chen^**

¹Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

²Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan

³Cardiovascular Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan

¹¹Cardiovascular Center, Taichung Veterans General Hospital, Taichung, Taiwan

Abstract

Background In the Early Treatment of Atrial Fibrillation for Stroke Prevention Trial (EAST-AFNET 4), early rhythm control was associated with better clinical outcomes for patients with atrial fibrillation (AF). However, the intervention arm had more structured and regular follow-up, and whether the better outcomes of patients assigned to rhythm control were solely due to “early” intervention or because of more regular and structured follow-up was unclear.

Objective In the present study, we aimed to investigate whether the findings of the EAST trial are applicable to the “real-world” clinical setting, where a less structured management protocol is operated.

Methods From 2001 to 2016, 301,064 newly diagnosed AF patients were identified from Taiwan National Health Insurance Research Database. Among these patients, 62,649 AF patients receiving antiarrhythmic drugs or catheter ablation within 1 year after AF being diagnosed (similar to the timing definition of the EAST-AFNET 4 trial) were categorized as the early rhythm control group, and the remaining 238,415 patients were defined as usual care group. Risks of clinical events were compared between the two groups.

Results Compared with usual care, early rhythm control was associated with a lower adjusted risk of ischemic stroke (adjusted hazard ratio [aHR]: 0.771, 95% confidence interval [CI]: 0.751–0.792; p < 0.001), heart failure (aHR: 0.851, 95% CI: 0.806–0.899; p < 0.001), acute myocardial infarction (aHR: 0.915, 95% CI: 0.877–0.955; p < 0.001), mortality (aHR: 0.794, 95% CI: 0.782–0.806; p < 0.001), and composite adverse events (aHR: 0.823, 95% CI: 0.813–0.834; p < 0.001). Compared with usual care, the lower risks of ischemic stroke (aHR: 0.746, 95% CI: 0.717–0.775), heart failure (aHR: 0.819, 95% CI: 0.798–0.841), mortality (aHR: 0.777, 95% CI: 0.759–0.795), and composite adverse events (aHR: 0.802, 95% CI: 0.787–0.818) associated with early rhythm control were even more evident when performed early (<3 months) compared to later periods (3–6 months, 7–9 months, and 10–12 months; p _int < 0.001). Principal results were generally consistent for majority of subgroups studied and among the cohort after propensity matching.

Conclusion In this nationwide cohort study, early rhythm control therapy was associated with a lower risk of adverse events compared with usual care among patients with early AF. Outcomes were even better with earlier (<3 months) intervention.

Keywords

atrial fibrillation - early rhythm control - ischemic stroke - mortality

Volltext

Referenzen

References
1 Chao TF, Liu CJ, Tuan TC. et al. Lifetime risks, projected numbers, and adverse outcomes in asian patients with atrial fibrillation: a report from the taiwan nationwide AF cohort study. Chest 2018; 153 (02) 453-466
2 Potpara TS, Lip GYH, Blomstrom-Lundqvist C. et al. The 4S-AF Scheme (Stroke Risk; Symptoms; Severity of Burden; Substrate): a novel approach to in-depth characterization (rather than classification) of atrial fibrillation. Thromb Haemost 2021; 121 (03) 270-278
3 Lip GYH. The ABC pathway: an integrated approach to improve AF management. Nat Rev Cardiol 2017; 14 (11) 627-628
4 Hindricks G, Potpara T, Dagres N. et al. ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association of Cardio-Thoracic Surgery (EACTS). Eur Heart J 2020
5 Chao TF, Joung B, Takahashi Y. et al. 2021 Focused update consensus guidelines of the Asia Pacific Heart Rhythm Society on Stroke Prevention in Atrial Fibrillation: executive summary. Thromb Haemost 2022; 122 (01) 20-47
6 Wyse DG, Waldo AL, DiMarco JP. et al; Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) Investigators. A comparison of rate control and rhythm control in patients with atrial fibrillation. N Engl J Med 2002; 347 (23) 1825-1833
7 Van Gelder IC, Hagens VE, Bosker HA. et al; Rate Control versus Electrical Cardioversion for Persistent Atrial Fibrillation Study Group. A comparison of rate control and rhythm control in patients with recurrent persistent atrial fibrillation. N Engl J Med 2002; 347 (23) 1834-1840
8 Marrouche NF, Brachmann J, Andresen D. et al; CASTLE-AF Investigators. Catheter ablation for atrial fibrillation with heart failure. N Engl J Med 2018; 378 (05) 417-427
9 Kirchhof P, Camm AJ, Goette A. et al; EAST-AFNET 4 Trial Investigators. Early rhythm-control therapy in patients with atrial fibrillation. N Engl J Med 2020; 383 (14) 1305-1316
10 Chao TF, Chiang CE, Liao JN, Chen TJ, Lip GYH, Chen SA. Comparing the effectiveness and safety of nonvitamin K antagonist oral anticoagulants and warfarin in elderly Asian patients with atrial fibrillation: a nationwide cohort study. Chest 2020; 157 (05) 1266-1277
11 Chao TF, Lip GYH, Liu CJ. et al. Relationship of aging and incident comorbidities to stroke risk in patients with atrial fibrillation. J Am Coll Cardiol 2018; 71 (02) 122-132
12 Chao TF, Lip GYH, Lin YJ. et al. Age threshold for the use of non-vitamin K antagonist oral anticoagulants for stroke prevention in patients with atrial fibrillation: insights into the optimal assessment of age and incident comorbidities. Eur Heart J 2019; 40 (19) 1504-1514
13 Tsai CT, Liao JN, Chiang CE. et al. Association of ischemic stroke, major bleeding, and other adverse events with warfarin use vs non-vitamin K antagonist oral anticoagulant use in patients with atrial fibrillation with a history of intracranial hemorrhage. JAMA Netw Open 2020; 3 (06) e206424
14 Chang TY, Chan YH, Chiang CE. et al. Risks and outcomes of gastrointestinal malignancies in anticoagulated atrial fibrillation patients experiencing gastrointestinal bleeding: A nationwide cohort study. Heart Rhythm 2020; 17 (10) 1745-1751
15 Chang CH, Lee YC, Tsai CT. et al. Continuation of statin therapy and a decreased risk of atrial fibrillation/flutter in patients with and without chronic kidney disease. Atherosclerosis 2014; 232 (01) 224-230
16 Cheng CL, Kao YH, Lin SJ, Lee CH, Lai ML. Validation of the National Health Insurance Research Database with ischemic stroke cases in Taiwan. Pharmacoepidemiol Drug Saf 2011; 20 (03) 236-242
17 Hsieh CY, Chen CH, Li CY, Lai ML. Validating the diagnosis of acute ischemic stroke in a National Health Insurance claims database. J Formos Med Assoc 2015; 114 (03) 254-259
18 Lin YS, Chen TH, Chi CC. et al. Different implications of heart failure, ischemic stroke, and mortality between nonvalvular atrial fibrillation and atrial flutter-a view from a national cohort study. J Am Heart Assoc 2017; 6 (07) 6
19 Cheng CL, Lee CH, Chen PS, Li YH, Lin SJ, Yang YH. Validation of acute myocardial infarction cases in the national health insurance research database in taiwan. J Epidemiol 2014; 24 (06) 500-507
20 Kaplan RM, Koehler J, Ziegler PD, Sarkar S, Zweibel S, Passman RS. Stroke risk as a function of atrial fibrillation duration and CHA₂DS₂-VASc score. Circulation 2019; 140 (20) 1639-1646
21 Sun W, Freedman B, Martinez C, Wallenhorst C, Yan BP. Atrial fibrillation detected by single time-point handheld electrocardiogram screening and the risk of ischemic stroke. Thromb Haemost 2022; 122 (02) 286-294
22 Wallenhorst C, Martinez C, Freedman B. Risk of ischemic stroke in asymptomatic atrial fibrillation incidentally detected in primary care compared with other clinical presentations. Thromb Haemost 2022; 122 (02) 277-285
23 Wachter R, Freedman B. Subclinical atrial fibrillation and the risk of recurrent ischemic stroke. Thromb Haemost 2021; 121 (06) 697-699
24 Guo Y, Lane DA, Wang L. et al; mAF-App II Trial Investigators. Mobile Health technology to improve care for patients with atrial fibrillation. J Am Coll Cardiol 2020; 75 (13) 1523-1534
25 Romiti GF, Pastori D, Rivera-Caravaca JM. et al. Adherence to the ‘Atrial Fibrillation Better Care’ pathway in patients with atrial fibrillation: impact on clinical outcomes-a systematic review and meta-analysis of 285,000 patients. Thromb Haemost 2022; 122 (03) 406-414
26 Proietti M, Romiti GF, Olshansky B, Lane DA, Lip GYH. Comprehensive management with the ABC (Atrial Fibrillation Better Care) pathway in clinically complex patients with atrial fibrillation: a post hoc ancillary analysis from the AFFIRM trial. J Am Heart Assoc 2020; 9 (10) e014932
27 Yao Y, Guo Y, Lip GYH. mAF-App II Trial investigators. The effects of implementing a mobile health-technology supported pathway on atrial fibrillation-related adverse events among patients with multimorbidity: the mAFA-II randomized clinical trial. JAMA Netw Open 2021; 4 (12) e2140071
28 Proietti M, Vitolo M, Harrison SL. et al; ESC-EHRA EORP-AF Long-Term General Registry Investigators. Real-world applicability and impact of early rhythm control for European patients with atrial fibrillation: a report from the ESC-EHRA EORP-AF long-term general registry. Clin Res Cardiol 2022; 111 (01) 70-84

Zusatzmaterial

Supplementary Material (PDF)