The Editorial Executive Committee welcomes letters, which should be less than 250 words. Before a decision to publish is made, letters which refer to a published article may be sent to the author for a response. Any letter may be sent to an expert for comment. When letters are published, they are usually accompanied in the same issue by their responses or comments. The Committee screens out discourteous, inaccurate or libellous statements. The letters are sub-edited before publication. Authors are required to declare any conflicts of interest. The Committee's decision on publication is final.

Letter to the Editor

The article on cardiovascular drugs in older people (Aust Prescr 2013;36:190-4) did not provide up-to-date evidence regarding the use of anticoagulants in older people. The elderly with atrial fibrillation are at the greatest risk of stroke.1,2Risk from falls has been an excuse not to treat. It is estimated that patients with atrial fibrillation, with an average stroke risk of 5% a year, would have to fall approximately 300 times in a year for the risk to outweigh the benefit.3

In people aged 75 years and over with atrial fibrillation, the risk of stroke may be greater than 20% a year and can be reduced to less than 5%.4,5In the ARISTOTLE trial,5apixaban was compared to warfarin in 18 201 patients. In the 5678 patients aged 75 and older, the rate of stroke or systemic embolism per year was only 1.6–2.2%. There was significantly less intracranial haemorrhage with apixaban.

Aspirin as a single drug may be marginally better than placebo, but with the risk of bleeding.6 Aspirin plus clopidogrel is better than aspirin alone, but the risk of bleeding is similar to warfarin.7 We agree with both the Canadian Cardiovascular Society and the European Society of Cardiology who no longer recommend antiplatelet therapy as first line in stroke prevention, irrespective of age, in patients with atrial fibrillation and a CHADS2 score of at least one.8,9

Anticoagulants for stroke prevention in the elderly with atrial fibrillation are indicated in most patients, even if they are frail. Antiplatelet drugs are markedly inferior with similar or greater bleeding risk.6,10,11

David Colquhuon
Cardiologist
Wesley Hospital
Toowong, Qld

Tan Banh
Intern
Mackay Base Hospital
Mackay, Qld

Author's comments

Vasi Naganathan, the author of the article, comments:

The letter raises an important question about the effectiveness and safety of anticoagulants for atrial fibrillation in older people. The authors are correct in their assertion that the evidence from clinical trials shows that anticoagulants are more effective than antiplatelets and have a similar low bleeding risk in the kind of older people who participate in clinical trials. The key question, however, is whether anticoagulants do more good than harm in older people who are frail, have multiple comorbidities and frequent falls. We do not have direct evidence about the efficacy or safety in this group because the inclusion and exclusion critera in anticoagulant trials exclude most of them.

In the ARISTOTLE trial,12 exclusion criteria included increased bleeding risk believed to be a contraindication to oral anticoagulation, severe comorbid condition with a life expectancy of less than one year, severe renal insufficiency and inability to comply with INR monitoring. Over 80% of the patients in the BAFTA trial13 were taking warfarin or aspirin before enrolment, which means the trial selected individuals who had already survived exposure to drugs that increase the risk of bleeding. In the much smaller WASPO trial14 which specifically enrolled octogenarians, people were excluded if they had had one or more falls within the last 12 months or a Mini-Mental State Examination (MMSE) score <26.

The assertion that a patient with atrial fibrillation must have 300 falls a year before the risk of warfarin outweighs the benefit comes from a Markov decision analysis that assumed participants had no disability at all before anticoagulation. It did not take into account the fact that patients who fall often have other risks for bleeding that can lead to major bleeds other than subdural haematomas.15

Unless someone is brave enough to do the definitive trial that specifically looks at anticoagulation in older patients with atrial fibrillation who are truly frail, have comorbidities and are at risk of falling, or we have anticoagulation registries that include these kind of patients, we are left making clinical decisions in an ‘evidence-free zone’ and we will continue to see a wide variation in clinical practice.

References

  1. Borowsky LH, Phillips KA, Selby JV, Go AS, Singer DE. Warfarin use among ambulatory patients with nonvalvular atrial fibrillation: the anticoagulation and risk factors in atrial fibrillation (ATRIA) study. Ann Intern Med 1999;131:927-34 .
  2. Leyden JM, Kleinig TJ, Newbury J, Castle S, Cranefield J, Anderson CS. Adelaide stroke incidence study: declining stroke rates but many preventable cardioembolic strokes. Stroke 2013;44:1226-31 .
  3. Anticoagulant-related bleeding in older persons with atrial fibrillation: physicians’ fears often unfounded. Arch Intern Med 2003;163:1580-6 .
  4. Broderick JP, Dyken M, Feinberg WM, Sacco RL, Easton JD. American Heart Association Prevention Conference. IV. Prevention and Rehabilitation of stroke. Risk factors. Stroke 1997;28:1507-17 .
  5. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2011;365:981-92 .
  6. Hart RG, Pearce LA, Aguilar MI. Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation. Ann Intern Med 2007;146:857-67 .
  7. ACTIVE Writing Group of the ACTIVE Investigators, Pogue J, Hart R, Pfeffer M, Hohnloser S. Clopidogrel plus aspirin versus oral anticoagulation for atrial fibrillation in the Atrial fibrillation Clopidogrel Trial with Irbesartan for prevention of Vascular Events (ACTIVE W): a randomised controlled trial. Lancet 2006;367:1903-12 .
  8. Skanes AC, Healey JS, Cairns JA, Gillis AM, McMurtry MS, Dorian P. Focused 2012 update of the Canadian Cardiovascular Society atrial fibrillation guidelines: recommendations for stroke prevention and rate/rhythm control. Can J Cardiol 2012;28:125-36 .
  9. Atar D, De Caterina R, Savelieva I, Hohnloser SH. 2012 focused update of the ESC Guidelines for the management of atrial fibrillation: an update of the 2010 ESC Guidelines for the management of atrial fibrillation. Developed with the special contribution of the European Heart Rhythm Association. Eur Heart J 2012;33:2719-47 .
  10. Warfarin versus aspirin for stroke prevention in an elderly community population with atrial fibrillation (the Birmingham Atrial Fibrillation Treatment of the Aged Study, BAFTA): a randomised controlled trial. Lancet 2007;370:493-503 .
  11. A randomised controlled trial of warfarin versus aspirin for stroke prevention in octogenarians with atrial fibrillation (WASPO). Age Ageing 2007;36:151-6 .
  12. Granger CB, Alexander JH, McMurray JJ, Lopes RD, Hylek EM, Hanna M, et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2011;365:981-92.
  13. Mant J, Hobbs FD, Fletcher K, Roalfe A, Fitzmaurice D, Lip GY, et al; Midland Research Practices Network (MidReC). Warfarin versus aspirin for stroke prevention in an elderly community population with atrial fibrillation (the Birmingham Atrial Fibrillation Treatment of the Aged Study, BAFTA): a randomised controlled trial. Lancet 2007;370:493-503.
  14. Rash A, Downes T, Portner R, Yeo WW, Morgan N, Channer KS. A randomised controlled trial of warfarin versus aspirin for stroke prevention in octogenarians with atrial fibrillation (WASPO). Age Ageing 2007;36:151-6.
  15. Man-Son-Hing M, Nichol G, Lau A, Laupacis A. Choosing antithrombotic therapy for elderly patients with atrial fibrillation who are at risk for falls. Arch Intern Med 1999;159:677-85.