Korean Circ J.  2024 Dec;54(12):811-821. 10.4070/kcj.2024.0073.

The Efficacy and Safety of NOAC in Very Elderly Atrial Fibrillation Patients: Data From the Korean National Health Insurance Cohort Registry

• Choi SH
• Lee YC
• Baek YS

• KMID: 2563795
• DOI: http://doi.org/10.4070/kcj.2024.0073

Abstract

Background and Objectives
We investigated the clinical benefit of anticoagulation with non-vitamin K antagonist oral anticoagulant (NOAC) in very elderly atrial fibrillation (AF) patients through national healthcare insurance registry.
Methods
Clinical data was acquired from the National Health Insurance Service of south Korea. Medical records of 862,935 patients who were diagnosed with AF from 2015 to 2020 were collected for analysis. Patients under the age of 85, prior history of intracranial hemorrhage, gastrointestinal bleeding and prior prescription days of aspirin, warfarin or NOAC exceeding 90 along with follow up period less than 90 days were excluded.
Results
A total of 10,625 patients were eligible for analysis. Patients with oral anticoagulant (hazard ratio [HR], 0.60, 95% confidence interval [CI], 0.53–0.69, p<0.001) showed higher efficacy regarding cerebrovascular accident (CVA) compared to aspirin (HR, 0.84, 95% CI, 0.74–0.95, p=0.008) and no treatment group. Individual comparison of NOAC and aspirin via propensity score matching showed that patients with NOAC (HR, 0.71, 95% CI, 0.61–0.85, p<0.001) showed higher event free survival regarding CVA compared to aspirin. Bleeding risk was also higher for NOAC (HR, 1.28, 95% CI, 1.07–1.56, p=0.006) group but did not result in commensurate increase in mortality (HR, 0.60, 95% CI, 0.45–0.81, p<0.001).
Conclusions
Anticoagulation with NOAC in very elderly patient showed higher event free survival regarding CVA. Despite having higher event rate of bleeding, eventual death was lower for NOAC.

Keyword

Atrial fibrillation; NOAC; Aspirin; Cerebrovascular accident

Figure

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  Figure 1 Flow chart of study population.AF = atrial fibrillation; GI = gastrointestinal; ICH = intracranial hemorrhage; NOAC = non-vitamin K antagonist oral anticoagulant; OAC = oral anticoagulant.

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  Figure 2 Kaplan-Meier plot for cerebrovascular accident (all study population).OAC = oral anticoagulant.

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  Figure 3 Kaplan-Meier plot for bleeding events (all study population).OAC = oral anticoagulant.

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  Figure 4 Kaplan-Meier plot for subgroup matched datasets (NOAC/aspirin, NOAC/warfarin).(A, B) Cerebrovascular accident. (C, D) Bleeding.NOAC = non-vitamin K antagonist oral anticoagulant.

Reference

1. Furberg CD, Psaty BM, Manolio TA, Gardin JM, Smith VE, Rautaharju PM. Prevalence of atrial fibrillation in elderly subjects (the Cardiovascular Health Study). Am J Cardiol. 1994; 74:236–241. PMID: 8037127.

2. Go AS. The epidemiology of atrial fibrillation in elderly persons: the tip of the iceberg. Am J Geriatr Cardiol. 2005; 14:56–61. PMID: 15785146.

3. Langenberg M, Hellemons BS, van Ree JW, et al. Atrial fibrillation in elderly patients: prevalence and comorbidity in general practice. BMJ. 1996; 313:1534. PMID: 8978233.

4. Go AS, Hylek EM, Phillips KA, et al. Prevalence of diagnosed atrial fibrillation in adults: national implications for rhythm management and stroke prevention: the AnTicoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study. JAMA. 2001; 285:2370–2375. PMID: 11343485.

5. Feinberg WM, Blackshear JL, Laupacis A, Kronmal R, Hart RG. Prevalence, age distribution, and gender of patients with atrial fibrillation. Analysis and implications. Arch Intern Med. 1995; 155:469–473. PMID: 7864703.

6. Ding WY, Blomström-Lundqvist C, Fauchier L, et al. Contemporary management of atrial fibrillation and the predicted vs. absolute risk of ischaemic stroke despite treatment: a report from ESC-EHRA EORP-AF Long-Term General Registry. Europace. 2023; 25:277–282. PMID: 36427202.

7. January CT, Wann LS, Calkins H, et al. 2019 AHA/ACC/HRS focused update of the 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association task force on clinical practice guidelines and the Heart Rhythm Society in collaboration with the Society of Thoracic Surgeons. Circulation. 2019; 140:e125–e151. PMID: 30686041.

8. Kim D, Yang PS, Joung B. Optimal rhythm control strategy in patients with atrial fibrillation. Korean Circ J. 2022; 52:496–512. PMID: 35790494.

9. Yoon M, Oh J, Chun KH, et al. Clinical implications of device-detected atrial fibrillation in cardiac resynchronization therapy. Korean Circ J. 2023; 53:483–496. PMID: 37271751.

10. Zuo ML, Liu S, Chan KH, et al. The CHADS₂ and CHA₂DS₂-VASc scores predict new occurrence of atrial fibrillation and ischemic stroke. J Interv Card Electrophysiol. 2013; 37:47–54. PMID: 23389054.

11. Gargiulo G, Goette A, Tijssen J, et al. Safety and efficacy outcomes of double vs. triple antithrombotic therapy in patients with atrial fibrillation following percutaneous coronary intervention: a systematic review and meta-analysis of non-vitamin K antagonist oral anticoagulant-based randomized clinical trials. Eur Heart J. 2019; 40:3757–3767. PMID: 31651946.

12. Jackson LR 2nd, Peterson ED, Okeagu E, Thomas K. Review of race/ethnicity in non vitamin K antagonist oral anticoagulants clinical trials. J Thromb Thrombolysis. 2015; 39:222–227. PMID: 25362508.

13. Gu ZC, Kong LC, Yang SF, et al. Net clinical benefit of non-vitamin K antagonist oral anticoagulants in atrial fibrillation and chronic kidney disease: a trade-off analysis from four phase III clinical trials. Cardiovasc Diagn Ther. 2019; 9:410–419. PMID: 31737513.

14. Sardar P, Chatterjee S, Chaudhari S, Lip GY. New oral anticoagulants in elderly adults: evidence from a meta-analysis of randomized trials. J Am Geriatr Soc. 2014; 62:857–864. PMID: 24786913.

15. Larsen TB, Skjøth F, Nielsen PB, Kjældgaard JN, Lip GY. Comparative effectiveness and safety of non-vitamin K antagonist oral anticoagulants and warfarin in patients with atrial fibrillation: propensity weighted nationwide cohort study. BMJ. 2016; 353:i3189. PMID: 27312796.

16. Chao TF, Liu CJ, Lin YJ, et al. Oral anticoagulation in very elderly patients with atrial fibrillation: a nationwide cohort study. Circulation. 2018; 138:37–47. PMID: 29490992.

17. Jeong JH, Choi JI. A ‘gender paradox’ of female as a stroke risk in atrial fibrillation: do women live longer than men? Korean Circ J. 2022; 52:604–605. PMID: 35929053.

18. Akashi S, Oguri M, Ikeno E, et al. Outcomes and safety of very-low-dose edoxaban in frail patients with atrial fibrillation in the ELDERCARE-AF randomized clinical trial. JAMA Netw Open. 2022; 5:e2228500. PMID: 35997978.

19. Okumura K, Lip GY, Akao M, et al. Edoxaban for the management of elderly Japanese patients with atrial fibrillation ineligible for standard oral anticoagulant therapies: rationale and design of the ELDERCARE-AF study. Am Heart J. 2017; 194:99–106. PMID: 29223441.

20. Rochmah TN, Rahmawati IT, Dahlui M, Budiarto W, Bilqis N. Economic burden of stroke disease: a systematic review. Int J Environ Res Public Health. 2021; 18:7552. PMID: 34299999.

21. Tan E, Gao L, Collier JM, et al. The economic and health burden of stroke among younger adults in Australia from a societal perspective. BMC Public Health. 2022; 22:218. PMID: 35114974.