Elsevier

The Lancet

Volume 377, Issue 9778, 14–20 May 2011, Pages 1681-1692
The Lancet

Series
Medical treatment in acute and long-term secondary prevention after transient ischaemic attack and ischaemic stroke

https://doi.org/10.1016/S0140-6736(11)60516-3Get rights and content

Summary

Stroke is a major cause of death and disability worldwide. Without improvements in prevention, the burden will increase during the next 20 years because of the ageing population, especially in developing countries. Major advances have occurred in secondary prevention during the past three decades, which demonstrate the broader potential to prevent stroke. We review the main medical treatments that should be considered for most patients with transient ischaemic attack or ischaemic stroke in the acute phase and the long term, and draw attention to recent developments.

Introduction

Stroke causes nearly 10% of all deaths worldwide.1 In 2002, stroke-related disability was the sixth most common cause of reduced disability-adjusted life-years,1 and stroke is predicted to rise to fourth in this list by 2030, partly because of the ageing population.2 The incidence of stroke is already higher than that of acute myocardial infarction in at least some regions.3 In developed countries, stroke accounts for more than 4% of direct health-care expenditure, with an absolute cost of about £9 billion in the UK and more than US$40 billion in the USA.4, 5 Stroke also has substantial indirect costs related to complications, such as post-stroke dementia, depression, falls, fractures, and epilepsy. Yet, the proportion of research funds directed towards stroke remains disproportionately low.6

Although primary prevention is most important in reduction of the burden of stroke, effective secondary prevention is also essential. About 30% of strokes occur in individuals with a previous transient ischaemic attack (TIA) or stroke,7 and more than 50% occur in individuals with previous vascular events of any kind.8 Recurrent strokes are more severe than first strokes and are more likely to cause dementia.9 However, much progress has been made in prevention of recurrent stroke,10 with evidence of effectiveness in randomised trials shown for aspirin in 1978, aspirin plus dipyridamole in 1987, warfarin for patients with atrial fibrillation in 1993, carotid endarterectomy for severe symptomatic carotid stenosis in 1991, clopidogrel in 1996, blood-pressure reduction in 2001, and cholesterol reduction with simvastatin in 2004 and atorvastatin in 2006. Most patients who have a TIA or stroke therefore end up taking several drugs long term.

The combined effect of all these different interventions on stroke risk cannot easily be derived from analysis of randomised trials, but can be seen in population-based studies that span the period over which they have been introduced. Figure 1 shows the risks of recurrent stroke in all patients in a UK population-based study presenting with TIA and non-disabling stroke in 2002–10 compared with those in the same population in 1981–86. Our review considers the evidence behind the interventions that have led to this improvement in outcome. Although surgical and vascular interventional techniques such as carotid endarterectomy and stenting have contributed to the improvement in outcomes,11, 12 their absolute effect at the population level is small. This review will therefore be confined to the medical treatments that should be considered for most patients with TIA or ischaemic stroke. Lifestyle modifications, such as smoking cessation, reduction of alcohol intake, increased exercise, or decisions about concomitant drugs such as hormone replacement therapy, will not be covered. Although the treatments used are similar in both circumstances, secondary prevention will be considered separately for the acute phase, which is regarded as the first 90 days, and for the long term thereafter, partly because of differences in the evidence base.

Section snippets

Prognosis and triage

Early estimates suggested that TIA and minor stroke were fairly benign conditions with a low risk of recurrent stroke (1–2% at 7 days and 2–4% at 1 month), but these estimates were based on studies in which patients were recruited weeks or months after their initial event.13 More recently, prospective studies from the time of the presenting event have shown that stroke risk is much higher after TIA14 and after minor stroke.15 A meta-analysis14 of 18 such studies reported a stroke risk of 3·1%

Background

The evidence base from randomised controlled trials for long-term secondary prevention of stroke is more robust than for than for acute prevention, although rates of appropriate treatment are often low.49, 50 We review the main medical therapeutic strategies.

Cerebral ischaemia of arterial origin

Appropriate use of antiplatelet drugs and anticoagulants after TIA or ischaemic stroke depends on whether the underlying cause is cardioembolic or of presumed arterial origin. Aspirin is recommended for secondary prevention after cerebral

Potential long-term benefits of aggressive multi-risk-factor control

Estimation of the combined effects of treatment of all major risk factors in secondary prevention of stroke is difficult. If one uses the observed treatment effects from randomised trials and assumes that the relative effects of each intervention are independent of the effects of the others, then treatment of all major risk factors is estimated to reduce the risk of recurrent stroke by about 80% compared with no treatment.131 A treatment effect of this size is supported by the observed

Conclusion

Secondary prevention with antiplatelet agents, antihypertensives, statins and anticoagulation, and carotid endarterectomy as appropriate should be initiated urgently after TIA or minor stroke because of the high risks of early stroke recurrence. For long-term secondary prevention, most guidelines recommend aspirin plus dipyridamole or clopidogrel as the first-line approach after cerebral ischaemia of arterial origin. With a cardiac origin, factor Xa and thrombin inhibitors are challenging the

Search strategy and selection criteria

Each of the authors is an expert in secondary stroke prevention. They continuously update their own literature databases from which they drew for this Review. Where possible, data from previous systematic reviews have been quoted.

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