Physicians' Academy for Cardiovascular Education

Good quality anticoagulation control important in high risk elderly AF patients

Literature - Senoo K and Lip GYH, Stroke 2015


Relationship of Age With Stroke and Death in Anticoagulated Patients With Nonvalvular Atrial Fibrillation: AMADEUS Trial

 
Senoo K and Lip GYH
Stroke. Originally published October 13, 2015. doi: 10.1161/STROKEAHA.115.010614
 

Background

The net clinical benefit of warfarin treatment in atrial fibrillation (AF)  to reduce the risk of ischemic stroke and all-cause mortality increases with age [1], but the absolute risk of bleeding during antithrombotic therapy is also larger with increasing age. Anticoagulation monitoring and drug compliance, and the existence of comorbidities can be a challenge among the elderly [2]. Consequently, elderly patients with AF may not be prescribed anticoagulation or are unable to maintain warfarin use over time. Thus, they may be exposed to a high risk of stroke [3].
Limited age-specific data on the incidence and risk factors of stroke and death in anticoagulated patients with non-valvular AF is available. Only the Birmingham Atrial Fibrillation Treatment of the Aged (BAFTA) trial [4] specifically investigated stroke prevention in AF patients of >75 years, and the Warfarin versus Aspirin for Stroke Prevention in Octogenarians with AF (WASPO) trial studied octogenarians [5].
This is a post hoc analysis of the efficacy and safety outcomes in an elderly anticoagulated AF cohort, namely the Evaluating the Use of SR34006 Compared to Warfarin or Acenocoumarol in Patients With Atrial Fibrillation (AMADEUS) trial [6]. This multicentre, randomised, open-label noninferiority study compared fixed-dose idraparinux with dose-adjusted oral vitamin K antagonist (VKA) therapy in patients with an indication for long-term anticoagulation. Incidence of adverse outcomes (stroke/systemic embolism [SSE], CV death) was investigated in 2293 anticoagulated patients with AF from the warfarin arm and time in therapeutic range (TTR) was related to clinical outcomes.
 

Main results

  • 2293 patients with AF on warfarin were categorised into tertiles by age (<67, 67-74 and >75 years). The primary endpoint of CV death and SSE events occurred in 3.8%, 2.9% and 1.4% per 100 patient-years (PY) in the top, middle and lowest tertile respectively.
  • Any clinically relevant bleeding occurred in 13.3%, 14.4% and 10.7% per 100 PY respectively in the age tertiles. Major bleeding was seen in 2.6%, 1.1% and 0.8% per 100 PY respectively.
  • In the well-controlled warfarin subgroup (TTR>60%), any clinically relevant bleedings were 7.4%, 9.2% and 8.6% per 100PY in the respective tertiles, and major bleedings occurred at a rate of 1.6%, 0.6% and 0.3% per 100 PY.
  • 8 out of 9 total ICH cases in the warfarin group had TTR<60%.
  • Higher absolute rates of the combined primary endpoint were seen with increasing age (P for trend=0.0005, HR: 2.63, 95%CI: 1.23-5.63 for top vs. lowest tertile, HR: 1.92, 95CI: 0.87-4.24 for middle vs. lowest tertile).
  • Absolute rates of any clinically relevant bleeding did not show a significant trend across age categories (P for trend: 0.55).
  • Men were younger than women (mean age men: 69+9 years, women: 72+8 years, P<0.001), but event rates for the primary outcome and any clinically relevant bleeding did not significantly differ between sexes.
  • TTR significantly negatively correlated with any clinically relevant bleeding (r=-0.91, P<0.001) and with CV death/SSE rates (r=-0.76, P=0.01).
 

Conclusion

Anticoagulated elderly AF patients are at high risk of CV death and SSE, and this risk increases with age. Age did not affect the risk of any clinically relevant bleeding. TTR did significantly negatively correlate with both the primary efficacy outcome and any clinically relevant bleedings.
 
Find this article online at Stroke
 

References

1. Hart RG, Pearce LA, Aguilar MI. Meta-analysis: antithrombotic therapy to prevent stroke in  patients who have nonvalvular atrial fibrillation. Ann Intern Med. 2007;146:857–867.
2. Singer DE, Chang Y, Fang MC, et al. The net clinical benefit of warfarin anticoagulation in atrial fibrillation. Ann Intern Med. 2009;151:297–305.
3. DiMarco JP, Flaker G, Waldo AL, et al; AFFIRM Investigators. Factors affecting bleeding risk during anticoagulant therapy in patients with atrial fibrillation: observations from the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study. Am Heart J. 2005;149:650–656. doi: 10.1016/j.ahj.2004.11.015.
4. Hylek EM, D’Antonio J, Evans-Molina C, et al. Translating the results of randomized trials into clinical practice: the challenge of warfarin candidacy among hospitalized elderly patients with atrial fibrillation. Stroke. 2006;37:1075–1080. doi: 10.1161/01. STR.0000209239.71702.ce.
5. Lip GY, Clementy N, Pericart L, et al. Stroke and major bleeding risk in elderly patients aged ≥75 years with atrial fibrillation: the Loire Valley atrial fibrillation project. Stroke. 2015;46:143–150. doi: 10.1161/STROKEAHA.114.007199.
6. Bousser MG, Bouthier J, Buller HR, et al, et al. Comparison of idraparinux with vitamin k antagonists for prevention of thromboembolism in patients with atrial fibrillation: a randomised, open-label, non-inferiority trial. Lancet. 2008;371:315–321.