Thrombolysis for acute stroke in Australia

In reply: We were delighted to hear of Waxman’s “miraculous” recovery, and admire the world-class standard of stroke care which was delivered at The Alfred.1 The Australian data in the Safe Implementation of Thrombolysis in Stroke (SITS) database up to 2008 included tertiary referral centres and outer metropolitan hospitals, and centres with varying experience of using recombinant tissue plasminogen activator (rt-PA) in clinical practice. There was no difference in outcomes according to experience of the treating centres. We believe that the non-trial clinical data presented in our article are a realistic indication of expected outcomes for all patients receiving thrombolysis for stroke in Australia.

The choice of a modified Rankin score (mRS) of 0–2 as an outcome measure in our article was largely dictated by the SITS international analysis. The aim of our study was to compare outcomes in Australia with those in the rest of the world; these were also not significantly different when an mRS of 0–1 was used as an outcome measure (mRS 0–1 at 3 months, 34.6% for Australia v 37.8% for the rest of the world; P = 0.13).

The original National Institute of Neurological Disorders and Stroke (NINDS) trial data,2 now more than 15 years old, have been analysed and re-analysed and, arguably, it is time to move on from rehashing the data. However, if one wishes to follow this path, there was in fact a significant difference in improvement at 24 hours between patients in the rt-PA and placebo groups. Smith’s statement that thrombolysis gives no greater improvement at 24 hours than placebo is correct in terms of the proportion of patients with an improvement in National Institutes of Health Stroke Scale (NIHSS) score of 4 or more, but this is a low benchmark and many untreated patients also show a relatively mild improvement at 24 hours. If one considers major neurological improvement (MNI, defined as an improvement in 24-hour NIHSS score of 8 or more), this was seen in a greater proportion of patients in the rt-PA group compared with the placebo group.3 Patients with MNI have a much greater chance of achieving minimal or no disability at 3 months, which is by far the most accepted outcome measure for thrombolytic therapy. This major early recovery is frequently seen in patients who receive rt-PA, and has been termed the “Lazarus effect”. Waxman was fortunate enough to experience this effect — but it occurs far too often with rt-PA in stroke to pass the Catholic Church criteria for a miracle.