By Harold L. Karpman, MD, FACC, FACP
Clinical Professor of Medicine, David Geffen School of Medicine at UCLA
Dr. Karpman reports no financial relationships relevant to this field of study.
SYNOPSIS: Aspirin administered early after the onset of transient ischemic attack symptoms substantially reduces the risk of developing a stroke.
SOURCE: Rothwell PM, Algra A, Chen Z, et al. Effects of aspirin on risk and severity of early recurrent stroke after transient ischemic attack and ischemic stroke: Time course analysis of randomized trials. Lancet 2016;388:365-375.
The risk of recurrent stroke is up to 10% in the week after a transient ischemic attack (TIA) or minor stroke occurs,1-4 and despite the fact that urgent medical treatment reduces that risk by as much as 80%, many patients inappropriately delay seeking medical attention for days or weeks, even when they make a correct self-diagnosis.5,6 Antithrombotic therapy, such as aspirin, has been recommended for the immediate management of most acute ischemic vascular events,7,8 but prehospital self-adminstration of aspirin has been discouraged after a TIA or stroke because of concerns about possible intracerebral hemorrhage. However, one must recognize that hemorrhages rarely cause TIA symptoms, accounting for < 5% of minor strokes.10,11
Because of the absence of published randomized evidence regarding the effect of aspirin on risk and severity of early recurrent stroke after TIA and minor stroke, Rothwell et al analyzed individual patient data and reviewed original paper records on early outcomes from all available trials of aspirin vs. placebo in secondary prevention after TIA or ischemic stroke. Investigators pooled data from 15,778 participants from 12 trials of aspirin vs. control in secondary prevention. They found that aspirin reduced the six-week risk of recurrent ischemic stroke by about 60% and disabling or fatal ischemic stroke by about 70%, with greatest benefit noted in patients presenting with TIA or minor stroke. The reduction in risk of recurrent ischemic stroke was most evident in patients with less severe baseline deficits and was substantial by the second day after starting aspirin treatment.
After analyzing the results of the pooled data, Rockwell et al concluded that the results confirmed the findings from previous nonrandomized studies regarding the effect of urgent treatment on the early risk of recurrent stroke,5,6,13 supporting the benefits of urgent treatment on the early risk of recurrent stroke. They suggested that most of the benefit of urgent treatment in these previous multi-intervention studies simply was due to aspirin and, therefore, believed it essential to emphasize that patients presenting with TIA or minor strokes should not be sent home from EDs with advice to add aspirin to their next prescription; rather, these patients should be treated acutely with aspirin. It follows that physicians should consider recommending the initiation of aspirin therapy if they suspect TIA — even on an initial telephone contact — if there are no obvious contraindications to aspirin therapy. Furthermore, Rothwell et al concluded that to initiate aspirin as soon as possible after the onset of symptoms, paramedics should administer aspirin therapy in appropriate instances when assessing patients at home. The authors found that other anticoagulant therapy, such as dipyridamole, was not as effective as aspirin, whereas clopidogrel plus aspirin appeared to be more effective than aspirin alone in terms of prevention of early recurrent stroke after TIA and minor ischemic stroke, but had no effect on the severity of the stroke. For longer-term prevention after TIA and ischemic stroke, aspirin demonstrated no significant effect on risk or severity of recurrent ischemic stroke after 12 weeks. However, the early benefit of aspirin was maintained on longer-term follow-up, even though no additional benefit accrued.
Clinicians should be aware that early treatment of TIA with aspirin reduced the six-week and 12-week risk of recurrent ischemic stroke by about 60%, and that adding dipyridamole was of no benefit except after 12 weeks, when it appeared to reduce the risk of recurrent ischemic stroke. The considerable benefits from early aspirin therapy in TIA patients warrants widespread patient education. However, one should recognize that this positive effect occurred for approximately 12 weeks, and that there was no reduction in risk of recurrent ischemic stroke after 12 weeks with aspirin therapy alone.
- Johnston SC, Gress DR, Browner WS, Sidney S. Short-term prognosis after emergency department diagnoses of TIA. JAMA 2000;284:
- Coull A, Lovett JK, Rothwell PM, for the Oxford Vascular Study. Population-based study of early risk of stroke after a transient ischemic attack or minor stroke: Implications for public education and organizations of services. BMJ 2004;328:326-328.
- Giles MF, Rothwell PM. Risk of stroke early after transient ischemic attack: A systematic review and meta-analysis. Lancet Neurol 2007;6:1063-1072.
- Johnston SC, Rothwell PM, Nguyen-Huynh MN, et al. Validation and refinement of scores to predict very early stroke risk after transient ischemic attack. Lancet 2007;369:283-292.
- Rothwell PM, Giles MF, Chandratheva A, et al., for the Early use of Existing Preventative Strategies for Stroke (EXPRESS) study. Major reduction in risk of early recurrent stroke by urgent treatment of TIA and minor stroke (EXPRESS study): A prospective population-based sequential comparison. Lancet 2007;370:1432-1442.
- Luengo-Fernandez R, Gray AM, Rothwell PM. Effect of urgent treatment for transient ischemic attack and minor stroke on disability and hospital costs (EXPRESS study): A prospective population-based sequential comparison. Lancet Neurol 2009;8:235-243.
- Rothwell PM, Algra A, Amarenco P. Medical treatment in acute and long-term secondary prevention after transient ischaemic attack and ischaemic stroke. Lancet 2011;377:1681-1692.
- Antithrombotic Trialists (ATT) Collaboration. Aspirin in the primary and secondary prevention of vascular disease: Collaborative meta-analysis of individual participant data from randomized trials. Lancet 2009;373:1849-1860.
- American Heart Association. Aspirin and Heart Disease. Available at: . Accessed April 13, 2016.
- Wardlaw JM, Keir SL, Dennis MS. The impact of delays in computed tomography of the brain on the accuracy of diagnosis and subsequent management in patients with minor stroke. J Neurol Neurosurg Psychiatry 2003;74:77-81.
- Lovelock CE, Redgrave JN, Briley D, Rothwell PM. Reliable estimation of the proportion of minor stroke due to intracerebral hemorrhage. Int J Stroke 2009;4:6-10.
- Wang X, Zhao X, Johnston SC, et al. Effect of clopidogrel with aspirin on functional outcome in TIA or minor stroke: CHANCE sub study. Neurology 2015;85:573-579.
- Lavallée PC, Meseguer E, Abboud H, et al. A transient ischemic attack clinic with round-the-clock access (SOS-TIA): Feasibility and effects. Lancet Neurol 2007;6:953-960.