Elderly benefit from early stroke therapy

Age should not be a bar to stroke treatment, say Dr Arvind Chandratheva and Dr Olivia Geraghty.

Data on the risks and benefits of treatment are often derived from trials in younger patients. Many randomised control trials (RCTs) also exclude patients with comorbidities, which reduces the eligibility of older patients.

But the likelihood that a patient will benefit from treatment often increases with age, as the absolute risk of a poor outcome without treatment increases. In addition the elderly population is continuing to rise.

Stroke prevention in the elderly illustrates many problems surrounding treatment decisions for older patients.

Stroke in the elderly
Both the STOP and the MRC trials of BP lowering in primary prevention showed that treatment reduced the risk of stroke by half.

All other things being equal, about 800 of the young hypertensives recruited in the MRC trial would have to be treated for one year to prevent one stroke, compared with about 70 of the elderly hypertensives recruited to the STOP trial.

The risk of stroke increases very steeply with age, and stroke in the elderly is associated with more disability, greater rehabilitation requirements, greater likelihood of needing nursing home care and increased mortality, compared with younger patients.

The early risk of major stroke after TIA or minor stroke is up to 20 per cent at 90 days, and is highest in patients with carotid stenosis or AF. This early risk also increases with age.

But secondary prevention of stroke, particularly the use of warfarin for patients with AF and the use of endarterectomy for symptomatic carotid stenosis, often raises the issue of appropriateness of treatment in the elderly.

We have therefore reviewed what is known about the determinants of risk and benefit in older patients of endarterectomy for symptomatic carotid stenosis and of warfarin after TIA or ischaemic stroke in patients with AF.

Carotid endarterectomy
Benefit from endarterectomy for symptomatic carotid disease depends on the degree of carotid stenosis. Surgery results in substantial absolute benefits in patients with 70-99 per cent stenosis.

Pooled analysis of RCTs showed that benefit from surgery was greatest in men, in those randomised to surgery within two weeks of the presenting event, and in patients aged over 75 years.

Fewer than 10 per cent of patients in the trials were over 75 years and there were very few octogenarians. However, a systematic review of all publications found that although operative mortality was increased for patients more than 75 years of age, operative risk of non-fatal stroke was not increased.

Since the trials showed that absolute benefit in patients aged over 75 years was significantly greater than in younger patients it is unlikely that this trend would be completely reversed in routine clinical practice. Therefore age alone should not be a bar to surgery.

Endarterectomy for asymptomatic carotid stenosis has been investigated in two large RCTs, The Asymptomatic Carotid Atherosclerosis Study and the Asymptomatic Carotid Surgery Trial.

The results were broadly similar with five-year absolute reductions in stroke risk following surgery of around 5 per cent. There was insufficient power to draw reliable conclusions about any benefits of surgery in the over 75 age group.

The absolute benefits derived from endarterectomy appear much lower for asymptomatic than symptomatic carotid stenosis.

Atrial fibrillation
Randomised trials of warfarin in non-rheumatic AF illustrate the difficulties of applying the results of research with confidence to older patients.

Also, AF incidence increases substantially with age and is a potent risk factor for ischaemic stroke.

There is strong evidence that adjusted dosage of warfarin is extremely effective in reducing the risk of ischaemic stroke in patients with non-valvular AF, with a 68 per cent reduction calculated by risk in pooled analysis of five RCTs.

However, complication rates in the trials were much lower than in routine practice. Fear of haemorrhage may prompt some physicians to avoid prescribing anticoagulants, especially in elderly patients.

The results of the Birmingham Atrial Fibrillation Treatment of the Aged trial have recently provided data on the effectiveness of warfarin in the elderly in a routine clinical practice setting. In this study, around 1,000 patients with AF aged 75 years or over were randomised to adjusted dosage warfarin (target INR 2-3) or aspirin 75mg per day and followed up for three years.

The primary endpoint was fatal or disabling stroke, intracranial haemorrhage or significant arterial embolism. There were 24 primary events in patients on warfarin and 48 primary events in patients on aspirin. The risk of major haemorrhage was similar in both groups.

Treatment for elderly
The conclusion was that warfarin is more effective than aspirin in stroke prevention in elderly people with AF and that the risks of haemorrhage of the two treatments are similar.

Available evidence shows that surgery for symptomatic carotid stenosis is highly effective in older patients, particularly if performed soon after the presenting TIA or stroke, and, unless contraindicated, warfarin should be used in elderly patients with AF.

More trials are needed in elderly patients, with inclusion of octogenarians, to gain a more concrete evidence base.

Dr Chandratheva and Dr Geraghty are research registrars at the department of clinical neurology, Oxford University.

References

  • Dahlof B, Lindholm L H, Hansson L et al. Morbidity and mortality in the Swedish Trial in Old Patients with Hypertension (STOP-Hypertension). Lancet 1991; 338: 1,281-5.
  • Durward Q J, Ragnarsson T S, Reeder R F, Case J L, Hughes C A. Carotid endarterectomy in nonagenarians. Arch Surg 2005; 140: 625-8
  • Rothwell P M, Eliasziw M, Gutnikov S A et al. Analysis of pooled data from the randomised controlled trials of endarterectomy for symptomatic carotid stenosis. Lancet 2003; 361: 107-16.
  • Bond R, Rerkasem K, Cuffe R, Rothwell P M. A systematic review of the associations between age and sex and the operative risks of carotid endarterectomy. Cerebrovasc Dis 2005; 20: 69-77.
  • Medical Research Council Working Party. MRC trial of treatment of mild hypertension. Br Med J 1985; 291: 97-104.
  • Rothwell P M, Eliasziw M, Gutnikov S A, Warlow C P, Barnett H J. Endarterectomy for symptomatic carotid stenosis in relation to clinical subgroups and timing of surgery. Lancet 2004; 363: 915-24.
  • Hart R G, Benavente O, McBride R, Pearce L A. Antithrombotic therapy to prevent stroke in patients with atrial fibrillation: a meta-analysis. Ann Intern Med 1999; 131: 492-501.
  • Mant J W, Richards S H, Hobbs F D et al. Protocol for Birmingham Atrial Fibrillation Treatment of the Aged study (BAFTA): a randomised controlled trial of warfarin versus aspirin for stroke prevention in the management of atrial fibrillation in an elderly primary care population. BMC Cardiovasc Disord 2003; 3: 9.

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