Urgency for TIA: Push Turns to Shove

Science Editorials and Reviews - Edited by S. Andrew Josephson, MD

December 13, 2007

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This editorial was developed for AAN.com, which is publishing expert opinions on a variety of hot topics in neurology.

S. Claiborne Johnston, MD, PhD
UCSF, Department of Neurology
Author Disclosure Statement

Summary

Several large-scale studies have shown that the risk of stroke is very high in the days to weeks following a transient ischemic attack (TIA). Two groups recently established urgent TIA clinics to evaluate and treat patients with TIA as soon as possible after presenting with symptoms. Both found that the risk of stroke was lower in those patients seen in these clinics, and suggest that the immediate initiation of aggressive therapies after TIA could substantially reduce the stroke risk in this population.

Introduction

The high risk of stroke in the days following TIA has now been well established. From 21 studies that have been careful to follow-up patients closely in the initial hours and days after diagnosis, the average stroke risk was 11% in the 90 days after a TIA, with half of the events occurring in the first 48 hours. These events have occurred in spite of standard treatment, such as antiplatelet therapy, statins, blood pressure control, endarterectomy, and anticoagulation for atrial fibrillation. However, initiation of optimal secondary prevention after TIA is far from complete and nearly always delayed.

Events can only be prevented if you intervene before they occur. Recognizing that most events were occurring in the first few days after TIA, the call to initiate treatment immediately after TIA has been made by some for years. Urgency in evaluation and treatment has only recently been incorporated into published guidelines, but the level of evidence supporting these recommendations has been relatively weak, based on the logic rather than specific studies comparing urgent to delayed initiation. 1 One notable exception is endarterectomy for symptomatic internal carotid artery stenosis, in which secondary analysis from pooled randomized trials demonstrates that endarterectomy within two weeks following a TIA or minor stroke is associated with much better outcomes than more delayed surgery.

Two recently published studies provide additional evidence suggesting that early reliable initiation of proven therapies after TIA may have substantial impact. 2 Though both were well done, neither study is a randomized trial, so results should be interpreted with caution.

The EXPRESS Study

Faced with high rates of stroke in their study in Oxford, England, and acknowledging delayed and incomplete initiation of secondary prophylaxis, the authors set up an urgent care clinic for patients diagnosed with TIA and minor stroke to replace one offering less aggressive care.2 The clinic was staffed to allow evaluation within 24 hours of an initial diagnosis, at least during week days. Hospitalization for TIA is infrequent in Britain. Without changing methods of case ascertainment, the authors compared care and outcomes before and after the clinic was initiated.

Most patients sent to the urgent TIA clinic were initiated on a statin, an antihypertensive medication, and an antithrombotic medication. Carotid imaging was done rapidly and endarterectomy was performed within seven days in 40% of appropriate candidates. Over the next 18 months, 90-day stroke risk declined to 2.1% among those seen in the urgent care clinic compared to 10.3% in the 18 months before it was initiated. For the 25% admitted to the hospital with TIA, there was no significant decline in 90-day stroke risk, which remained at 11.9%. The authors did not identify any differences in selection of patients for clinic evaluation over time, but this was an observational study so this cannot be certain. Nonetheless, the decline was impressive and appeared to begin immediately after the urgent care clinic was started.

The SOS Study

A similar urgent care clinic for TIA started in Paris, accepting referrals on weekdays for patients with recent TIA. 3 Though there was delay in evaluating some patients, most were seen within 24 hours of the initial event. Among those seen within 24 hours of symptom onset, the 90-day risk of stroke was 1.6% compared to an expected rate of 6.5% based on distribution of ABCD2 scores, a prognostic scheme that has been validated in multiple settings. Rates of stroke were not monitored prior to initiation of the new clinic. Again, this is an observational study and there is no control group, but the findings are at least suggestive.

Is It Real?

  • Both these studies concluded that risk reductions of 80% are possible simply by optimizing proven therapies after TIA. This is not inconsistent with theory as long as each proven intervention is used and works independently, and if the comparison is with doing nothing proven. Of course, treatment in these studies was much better than prior but still was not optimal, and there was significant prior usage of proven treatments in Oxford and in the cohorts of patients used for comparison in the SOS study. So, unless these interventions work better in these patients than in the previous trials, 80% risk reductions are probably not realistic.
  • Of course, it is possible that these interventions work even better in these high risk patients. Also, about half the patients in the Oxford study received both aspirin and clopidogrel 75 mg daily after an initial load of 300 mg. A pilot randomized trial called FASTER, published alongside the SOS study, found that this regimen was associated with a 36% risk reduction for stroke when given immediately following TIA. 4 The study was small and the result nonsignificant, but it does support the need for more data on this combination when given acutely.

Conclusion

Do antiplatelet agents, statins, antihypertensives, anticoagulation for patients with atrial fibrillation, and endarterectomy for symptomatic high grade carotid stenosis work? Absolutely. There are solid large-scale trials supporting each of these interventions. Are they going to work better if initiated sooner? Even without specific trials or observational studies, given the high risk of stroke, it would be stunning if they did not help patients more when initiated sooner. In light of this, the findings from these two new studies are not surprising and provide a needed shove behind the message that we must begin treatment immediately following TIA. I don't believe we are done with the existing armamentarium, however. In the FASTER trial, 11% treated with aspirin alone still had a new stroke within 90 days after TIA or minor stroke, and these patients were generally treated optimally. We need more effective treatments, and this will require additional trials targeting these high-risk patients.

Acknowledgment

The author thanks S. Andrew Josephson, MD, for his review of the manuscript.

References

  1. Johnston SC, Nguyen-Huynh MN, Schwarz ME, et al. National Stroke Association guidelines for the management of transient ischemic attacks. Annals of Neurology 2006;60:301-313.
  2. Rothwell PM, Giles MF, Chandratheva A, et al. Effect of urgent treatment of transient ischaemic attack and minor stroke on early recurrent stroke (EXPRESS study): a prospective population-based sequential comparison. Lancet 2007;370:1432-1442.
  3. Lavallee PC, Meseguer E, Abboud H, et al. A transient ischaemic attack clinic with round-the-clock access (SOS-TIA): feasibility and effects. Lancet Neurol 2007;6:953-960.
  4. Kennedy J, Hill MD, Ryckborst KJ, Eliasziw M, Demchuk AM, Buchan AM. Fast assessment of stroke and transient ischaemic attack to prevent early recurrence (FASTER): a randomised controlled pilot trial. Lancet Neurol 2007;6:961-969.

Author Disclosure

Dr. Johnston has nothing to disclose.