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Stroke prevention in older patients: How can you protect those who need it most?

Patient case: Evidence-based protection for older patients

 
Patient case: Evidence-based protection for older patients

How would you approach the treatment of the following fictional patient?

  • Anita is a 78-years-old former university lecturer who lives with her husband of 49 years
  • During her retirement, Anita has had more time to explore her love for painting, participating in an art class every week
  • She has four young grandchildren who she enjoys visiting whenever she can
  • Two years ago, Anita noticed that she felt frequently breathless and faint, and she was referred for an electrocardiogram upon a visit to her doctor. The results showed that Anita had atrial fibrillation (AF).

 

Anita’s doctor explained that she is at an increased risk of cardiovascular events due to her AF diagnosis. Having seen friends hospitalized for lengthy periods due to stroke, she is very fearful of the consequences of suffering from a stroke and being separated from her family.

 

What can you do to protect your older patients, like Anita, from these devastating outcomes?

Older patients are particularly vulnerable to stroke 

Advancing age is an independent risk factor for AF3 and, consequently, many strokes in older patients are related to AF. The risk of stroke in patients with AF is raised by 45% per decade of age.4 Older patients who suffer a stroke will be in hospital for longer, are less likely to be discharged to their homes and are at an increased risk of death compared with younger patients.2

Advancing age elevates the risk of stroke of in patients with AF4

Advancing age elevates the risk of stroke of in patients with AF4
AF, atrial fibrillation
 

Anticoagulation is the cornerstone of stroke prevention therapy in patients with AF.5 However, older patients also have an increased risk of bleeding. The incidence of major bleeding in patients aged ≥80 years receiving warfarin is three times higher than in patients aged <80 years.6 Due to this increased risk of bleeding, there is a significant underuse of anticoagulation agents in older patients despite their high stroke risk.7

 

The European Society of Cardiology (ESC) guidelines highlight the benefits of anticoagulation, stating that ‘Frailty, co-morbidities and increased risk of falls do not outweigh the benefits of oral anticoagulation given the small absolute risk of bleeding in anticoagulated elderly patients’.5 This sentiment is echoed in the ThrombosisAdviser podcast by Dr Christian Ruff, who commented, ‘I think you have to be very careful to use an age threshold or frailty assessment, even though we're not very good at assessing frailty, to deny anticoagulation, because the majority of patients, even elderly with co-morbidities, will benefit from anticoagulation.

 

How can you best protect your vulnerable older patients from stroke?

Subanalyses of four phase III trials investigating the efficacy and safety of non-vitamin K antagonist oral anticoagulants (NOACs; apixaban, dabigatran, edoxaban and rivaroxaban) in patients with AF aged ≥75 years demonstrated the consistency of the efficacy and safety profiles of these drugs in this older population, compared with patients aged <75 years.8-11

 

Of the four trials, the rivaroxaban trial, ROCKET AF, enrolled the highest proportion of patients aged ≥75 years, with these patients also having the highest mean CHADS2 (Congestive heart failure, Hypertension, Age ≥75 years, Diabetes mellitus, Stroke or transient ischaemic attack [2 points]) score.8-11
 

] ROCKET AF included a larger proportion of older patients (who are at increased risk of stroke) than other phase III NOAC

ROCKET AF included a larger proportion of older patients (who are at increased risk of stroke) than other phase III NOAC trials8-11
CHADS2, Congestive heart failure, Hypertension, Age ≥75 years, Diabetes mellitus, Stroke or transient ischaemic attack (2 points) 

The net clinical benefit of rivaroxaban compared with warfarin was shown to be greatest in patients aged ≥75 years. The protection from life-threatening bleeding events and all-cause mortality with rivaroxaban was as effective as with warfarin, and these patients were significantly more likely to be protected from non-haemorrhagic stroke than patients <75 years when receiving rivaroxaban compared with warfarin.11

The net clinical benefit of rivaroxaban versus warfarin is greatest in patients with AF aged ≥75 years

The net clinical benefit of rivaroxaban versus warfarin is greatest in patients with AF aged ≥75 years11

Reassuringly, the protection provided by rivaroxaban for older patients in a routine clinical setting has been shown to be consistent with results from randomized controlled trials.12 The protection of French patients with AF aged ≥80 years from ischaemic strokes and mortality was as effective with rivaroxaban as with vitamin K antagonists. Furthermore, a significant reduction in major bleeding and intracerebral haemorrhage events was shown with rivaroxaban compared with vitamin K antagonists in older patients, demonstrating that rivaroxaban can provide these patients with the protection they deserve.12

Real-world evidence demonstrates that rivaroxaban protects patients with AF from major bleeding and intracerebral haemorrhage events

Real-world evidence demonstrates that rivaroxaban protects patients with AF from major bleeding and intracerebral haemorrhage events12
CI, confidence interval; GI, gastrointestinal; HR, hazard ratio; NS, not significant; PS, propensity score; VKA, vitamin K antagonist

Dr Christian Ruff considers this particularly important. He noted, ‘As age is such a strong driver of stroke, [older] patients actually derive the greatest benefit from NOACs… It's safe to anticoagulate patients in their 80s, 90s, even above, because the risk of intracranial haemorrhage, which is the most feared and devastating consequence of anticoagulation, is vanishingly low with all of the NOACs’.

 

 

Providing consistent protection for all patients with AF

Older patients often have other risk factors that make them vulnerable to stroke. Diabetes, impaired kidney function and frailty all confer an increased risk of stroke to patients with AF.13-15

 

It is encouraging that the protection from stroke provided by NOACs is consistent in patients with AF with diabetes or impaired kidney function.16 Rivaroxaban has also demonstrated a reduction in stroke and systemic embolism compared with warfarin in frail patients with AF, without altering the risk of major bleeding.17

Many factors increase the risk of stroke in patients with AF

Many factors increase the risk of stroke in patients with AF13-15
AF, atrial fibrillation

For older patients with AF, like Anita, a once-daily regimen may prove beneficial, as it is associated with significantly improved adherence of patients to medication.18 Rivaroxaban offers simplicity and convenient dosing for all types of patients with AF. A single daily dose of rivaroxaban 20 mg offers your patients the protection they deserve, whilst a simple dose reduction to rivaroxaban 15 mg once daily can provide consistent protection for patients with a creatinine clearance of 15–49 ml/min/1.73 m2.19

 

This convenience is highlighted by Dr Christian Ruff, who commented, ‘One of the nice things… about rivaroxaban is that the dosing is very simple. As soon as the creatinine clearance goes less than 50 [ml/min/1.73 m2], they’re on the 15 milligrams daily for stroke prevention. And obviously, that's the same regardless if their creatinine clearance the next year is 45 than 35 [ml/min/1.73 m2], so you have this broad window.’
 

Looking forward

When considering how best to protect your older patients, like Anita, from their high risk of stroke, the evidence demonstrates that NOACs provide effective protection without an increased risk of bleeding. Real-world evidence and a net clinical benefit analysis further support the use of rivaroxaban, which has the benefit of simple and convenient dosing, in this vulnerable population. 
 

References
  • Yousufuddin M, Young N. Aging and ischemic stroke. Aging (Albany N Y) 2019;11:2542–2544. Return to content
  • Saposnik G, Cote R, Phillips S et al. Stroke outcome in those over 80: a multicenter cohort study across Canada. Stroke 2008;39:2310–2317. Return to content
  • 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
  • Hindricks G, Potpara T, Dagres N et al. 2020 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 2021;42:373–498. Return to content
  • Hylek EM, Evans-Molina C, Shea C et al. Major hemorrhage and tolerability of warfarin in the first year of therapy among elderly patients with atrial fibrillation. Circulation 2007;115:2689–2696. Return to content
  • Ogilvie IM, Newton N, Welner SA et al. Underuse of oral anticoagulants in atrial fibrillation: a systematic review. Am J Med 2010;123:638–645. 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
  • 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
  • Hanon O, Vidal JS, Pisica-Donose G et al. Bleeding risk with rivaroxaban compared with vitamin K antagonists in patients aged 80 years or older with atrial fibrillation. Heart 2020: doi:10.1136/heartjnl-2020-317923. Return to content
  • Stroke Risk in Atrial Fibrillation Working Group. Independent predictors of stroke in patients with atrial fibrillation: a systematic review. Neurology 2007;69:546–554. 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
  • Olesen JB, Lip GYH, Kamper AL et al. Stroke and bleeding in atrial fibrillation with chronic kidney disease. N Engl J Med 2012;367:625–635. 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
  • 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:e008643. Return to content
  • Salmasi S, Loewen PS, Tandun R et al. Adherence to oral anticoagulants among patients with atrial fibrillation: a systematic review and meta-analysis of observational studies. BMJ Open 2020;10:e034778. Return to content
  • Bayer AG. Xarelto® (rivaroxaban) Summary of Product Characteristics. 2021. Available at: https://www.ema.europa.eu/documents/product-information/xarelto-epar-product-information_en.pdf [accessed 8 June 2021] Bayer AG. Xarelto® (rivaroxaban) Summary of Product Characteristics. 2021. Available at: https://www.ema.europa.eu/documents/product-information/xarelto-epar-product-information_en.pdf [accessed 8 June 2021] Return to content

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