Older Patients with AF
This section looks at the epidemiology of age in patients with AF and examines how a patient’s age affects prognosis and treatment
In this section:
Epidemiology
Advancing age is a prominent risk factor for atrial fibrillation (AF).1 Furthermore, amongst patients with AF, age increases the risk of stroke by 1.5-fold per decade.2 This association is typically related to age-related complications, such as frailty, renal impairment, heart failure, hypertension and cognitive impairment, which worsen the prognosis of patients with AF.3,4 Older patients may be living independently, and a stroke event is likely to change the lives of these patients dramatically. Therefore, older people represent a large group of high-risk patients living with AF that we need to protect, with the global burden only expected to increase.1
Older patients with AF are at increased risk of stroke2
Because of their elevated risk of stroke, older patients with AF stand to benefit greatly from anticoagulation, and evidence suggests that these benefits outweigh the risk of bleeding. Despite this, they are among the least likely to receive anticoagulation.2,3,5
Strokes related to AF are largely preventable with appropriate treatment,6 therefore it’s of utmost importance to protect the independence and future of older people living with AF.
Clinical evidence
Subanalyses of patients with AF aged ≥75 years in the phase III clinical studies of non-vitamin K antagonist oral anticoagulants (NOACs; rivaroxaban, apixaban, dabigatran or edoxaban) demonstrated that the efficacy and safety profiles of anticoagulation did not differ with age.7-10 A meta-analysis of these clinical studies further confirmed these findings.11
The ROCKET AF study of rivaroxaban included the highest percentage of older patients (aged ≥75 years) out of all the phase III NOAC studies. These older patients also had the highest average CHADS2 score and the highest percentage of complications including congestive heart failure, diabetes and prior stroke or transient ischaemic attack.7-10
The results of ROCKET AF were consistent with real-world observations, such as those in the phase IV XANTUS study, in which rivaroxaban was associated with low rates of stroke and bleeding events in a broad population of patients with AF, and included 37% of patients aged >75 years.12
Further real-world evidence comes from the prospective, observational SAFIR cohort study of 995 patients aged ≥80 years with AF, where major bleeding events were significantly lower with rivaroxaban compared with vitamin K antagonists (VKAs) at 1 year.13 In addition, according to one-year clinical outcomes pooled from large European registries PREFER in AF and PREFER in AF PROLONGATION, NOAC use was associated with a better net clinical benefit compared with VKAs in 3,825 patients aged ≥75 years with AF, primarily because of the lower rates of major bleeding events.14
It is also reassuring that the retrospective analyses involving frail patients with AF who are typically older, confirmed that rivaroxaban reduced the risk of stroke at 2 years compared with warfarin without altering the risk of major bleeding events.15
These studies suggest that NOACs reduce the risk of stroke compared with VKAs regardless of age, with comparable or lower rates of major bleeding events. Because the evidence highlights that age is not a reason to withhold anticoagulation, more could be done to protect the older population with AF.
Treatment guidelines
European and American guidelines recommend anticoagulation for men with a CHA2DS3-VASc score ≥2 and women with a score ≥3; oral anticoagulation should be considered in men with a score ≥1 and in women with a score ≥2. In practice, because the female gender accounts for a score of 1 each, in the presence of an additional risk factor, all patients should be at least considered for oral anticoagulation.5,16
Age is one of the risk factors considered in this score, with an age ≥75 years accounting for a score of 2 and an age >65 years for a score of 1. Therefore, anticoagulation is recommended in patients aged ≥75 years even if they don’t have other risk factors, and in patients aged >65 years with at least one other risk factor. In patients aged >65 years with no additional risk factors, anticoagulation should still be considered.5,16
ESC and ACC/AHA/HRS guidelines for the management of AF recommend NOACs over VKAs for the treatment of NOAC-eligible patients.5,16 An important consideration for the use of NOACs is dose reductions that might apply to older patients. Apixaban or dabigatran have specific label guidance for recommended dose reductions in patients aged ≥80 years.17,18 Furthermore, because age is associated with declines in renal function, guidance for reduced NOAC doses in this population may need to be considered.17-21 More information on dose reductions in patients with AF and renal impairment can be found here .
See knowledge base section on ‘Patients with Renal Impairment’
References
- Zathar Z, Karunatilleke A, Fawzy AM, Lip GYH. Atrial Fibrillation in Older People: Concepts and Controversies. Frontiers in medicine 2019;6:175. Return to content
- van Walraven C, Hart RG, Connolly S et al. Effect of age on stroke prevention therapy in patients with atrial fibrillation: the atrial fibrillation investigators. Stroke 2009;40:1410-1416. Return to content
- Patti G, Lucerna M, Pecen L et al. Thromboembolic risk, bleeding outcomes and effect of different antithrombotic strategies in very elderly patients with atrial fibrillation: a sub-analysis from the PREFER in AF (PREvention oF Thromboembolic Events-European Registry in Atrial Fibrillation). J Am Heart Assoc 2017;6:e005657. Return to content
- Madhavan M, Holmes DN, Piccini JP et al. Association of frailty and cognitive impairment with benefits of oral anticoagulation in patients with atrial fibrillation. Am Heart J 2019;211:77-89 Return to content
- Kirchhof P, Benussi S, Kotecha D et al. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J 2016;37:2893–2962. Return to content
- Freedman B, Potpara TS, Lip GY. Stroke prevention in atrial fibrillation. Lancet 2016;388:806-817. Return to content
- Halperin JL, Hankey GJ, Wojdyla DM et al. Efficacy and safety of rivaroxaban compared with warfarin among elderly patients with nonvalvular atrial fibrillation in the Rivaroxaban Once Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF). Circulation 2014;130:138–146. Return to content
- Halvorsen S, Atar D, Yang H et al. Efficacy and safety of apixaban compared with warfarin according to age for stroke prevention in atrial fibrillation: observations from the ARISTOTLE trial. Eur Heart J 2014;35:1864–1872. Return to content
- Lauw MN, Eikelboom JW, Coppens M et al. Effects of dabigatran according to age in atrial fibrillation. Heart 2017;103:1015–1023. Return to content
- Kato ET, Giugliano RP, Ruff CT et al. Efficacy and safety of edoxaban in elderly patients with atrial fibrillation in the ENGAGE AF-TIMI 48 trial. J Am Heart Assoc 2016;5:e003432. Return to content
- Ruff CT, Giugliano RP, Braunwald E et al. Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials. Lancet 2014;383:955–962. Return to content
- Camm AJ, Amarenco P, Haas S et al. XANTUS: a real-world, prospective, observational study of patients treated with rivaroxaban for stroke prevention in atrial fibrillation. Eur Heart J 2016;37:1145–1153. Return to content
- Hanon O, Chaussade E, David JP et al. SAFIR cohort: One-year prospective follow-up of very old and frail patients treated with direct oral anticoagulant, rivaroxaban. Arch Cardiovasc Dis Suppl 2020;12:115. Return to content
- Patti G, Pecen L, Lucerna M et al. Net clinical benefit of non-vitamin K antagonist vs vitamin K antagonist anticoagulants in elderly patients with atrial fibrillation. Am J Med 2019;132:749–757. Return to content
- Martinez BK, Sood NA, Bunz TJ, Coleman CI. Effectiveness and safety of apixaban, dabigatran, and rivaroxaban versus warfarin in frail patients with nonvalvular atrial fibrillation. J Am Heart Assoc 2018;7. Return to content
- 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. Return to content
- Bristol Myers Squibb, Pfizer. Eliquis® (apixaban) Summary of Product Characteristics. 2020. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002148/WC500107728.pdf [accessed 30 July 2020]. Bristol Myers Squibb, Pfizer. Eliquis® (apixaban) Summary of Product Characteristics. 2020. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002148/WC500107728.pdf [accessed 30 July 2020]. Return to content
- Boehringer Ingelheim International GmbH. Pradaxa® (dabigatran etexilate) Summary of Product Characteristics. 2020. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000829/WC500041059.pdf [accessed 30 July 2020]. Boehringer Ingelheim International GmbH. Pradaxa® (dabigatran etexilate) Summary of Product Characteristics. 2020. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000829/WC500041059.pdf [accessed 30 July 2020]. Return to content
- Bayer AG. Xarelto® (rivaroxaban) Summary of Product Characteristics. 2020. Available at: https://www.ema.europa.eu/documents/product-information/xarelto-epar-product-information_en.pdf [accessed 30 July 2020]. Bayer AG. Xarelto® (rivaroxaban) Summary of Product Characteristics. 2020. Available at: https://www.ema.europa.eu/documents/product-information/xarelto-epar-product-information_en.pdf [accessed 30 July 2020]. Return to content
- Daiichi Sankyo Europe GmbH. Lixiana® (edoxaban) Summary of Product Characteristics. 2020. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002629/WC500189045.pdf [accessed 30 July 2020]. Daiichi Sankyo Europe GmbH. Lixiana® (edoxaban) Summary of Product Characteristics. 2020. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002629/WC500189045.pdf [accessed 30 July 2020]. Return to content
- Beyer-Westendorf J, Kreutz R, Posch F, Ay C. The CHA2DS2-VASc score strongly correlates with glomerular filtration rate and predicts renal function decline over time in elderly patients with atrial fibrillation and chronic kidney disease. Int J Cardiol 2018;253:71-77. Return to content