to the editor: I would like to clarify some of the recommendations from the article, “Transient Ischemic Attacks: Part I. Diagnosis and Evaluation,¹” that appeared in American Family Physician. The authors advocate early referral to the emergency department for evaluation and potential treatment with tissue-type plasminogen activator (tPA). They also place this recommendation in their algorithm (Figure 1). Transient ischemic attack (TIA) is not an indication for tPA administration; only confirmed strokes have received this indication. In fact, rapidly improving symptoms, as can occur with TIAs, are a contraindication to the administration of tPA.

Further, there has been much discussion about the role of tPA in patients who have suffered a stroke. Many authorities often quote a 30 percent reduction in disability with this intervention. For the record, the National Institute of Neurological Diseases and Stroke (NINDS) study group demonstrated a 12 percent absolute reduction in disability (number needed to treat [NNT] = 8).² The 30 percent figure that often is quoted (including in the Advanced Cardiac Life Support provider manual³) is relative risk reduction, which is a statistic that is commonly employed to exaggerate the benefits of an intervention. Further, it is always important to point out the harm associated with tPA administration in stroke patients. NINDS demonstrated a 6 percent deterioration caused by intracranial hemorrhage (NNT = 16). The use of tPA in the community hospital setting has been demonstrated to be fraught with problems.⁴

I agree with the current conclusions of the Cochrane Collaboration: “The data are promising and may justify the use of thrombolytic therapy with intravenous recombinant tissue plasminogen activator in experienced centres in highly selected patients where a [license] exists. However, the data do not support the widespread use of thrombolytic therapy in routine clinical practice at this time, but suggest that further trials are needed to identify which patients are most likely to benefit from treatment and the environment in which it may best be given.”⁵

in reply: I thank Dr. Dachs for his interest in the article.¹ We are in agreement that a patient with an accurately diagnosed resolved transient ischemic attack (TIA), defined by the current criteria (transient cerebral ischemic deficit lasting for at least one hour) or by the traditional definition (lasting for at least 24 hours), is not a candidate for tissue-type plasminogen activator (tPA) in the nonacute setting. At the time of an acute cerebral ischemia event, to which the algorithm pertains, the evaluating physician has no way of predicting if the deficit will clear or if it will remain permanent, and, therefore, this presentation could be a TIA or a stroke. For this reason, it is appropriate to evaluate a patient who presents with acute symptoms lasting less than 180 minutes for treatment with intravenous tPA regardless of whether the patient ultimately is diagnosed with a TIA or stroke. The National Institute of Neurological Diseases and Stroke (NINDS) trial for tPA in acute stroke contained a placebo limb and a treatment limb that consisted of potential TIAs and stroke patients. It is not appropriate to wait for patients to clear their symptoms of TIA in the acute setting because “time is brain.” As Dr. Dachs points out, rapidly improving symptoms or signs may indicate resolution of the cerebral ischemia, in which case the risks of intravenous tPA outweigh the benefits. Interestingly, there are data to suggest that although patients might be excluded at the time of initial evaluation for intravenous tPA on the basis of “mild or significantly improving neurologic symptoms,” 32 percent of such patients in one study were deemed dependent at discharge (or deceased).²

My article¹ was a review of the evaluation and treatment of TIA and not of the evaluation or treatment of acute stroke. The points that Dr. Dachs makes about the administration of tPA for acute stroke are well addressed in a previous article in American Family Physician.³ This article³ states “that the use of tPA in community hospitals is feasible and safe as long as the American Heart Association (AHA) guidelines and NINDS protocol are followed.”⁴ The use of tPA for acute ischemic stroke according to strict guidelines has been endorsed by the AHA Stroke Council [now the American Stroke Association] and the American Academy of Neurology. The U.S. Food and Drug Administration approved tPA 11 years ago, and after more than a decade of experience and use, intravenous tPA remains endorsed by these and other related foundations and academies.