Thrombolysis for acute stroke in Australia

To the Editor: Waxman’s prompt recovery after a stroke was probably a stroke of luck,1 unless perhaps Saint Mary MacKillop was involved. Amid the conflicting evidence on the effect of thrombolysis on recovery in ischaemic stroke, one fact is beyond doubt — thrombolysis gives no greater improvement at 24 hours than placebo.2 It is the various measures of recovery at 3 months, and the risks of adverse outcomes from protocol violations in administering thrombolysis, that are less clear.

The European Cooperative Acute Stroke Study III (ECASS III) showed that there is a benefit from administering thrombolysis up to 4.5 hours after stroke onset,3 and the complete Safe Implementation of Thrombolysis in Stroke International Stroke Thrombolysis Register (SITS-ISTR) data showed that this benefit can be reproduced in non-trial hospital practice.4 Simpson and colleagues say that the Australian data support this conclusion, even though outcomes show slightly higher mortality compared with rest-of-world data.5

There are several gaps in that line of reasoning. A modified Rankin score (mRS) of 0–1 (zero or minimal disability) is the standard measure of a good outcome. In ECASS III, an mRS of 0–1 was seen in 52.4% of patients who received thrombolysis compared with 45.1% of patients who received placebo.3 However, the SITS-ISTR data showed an mRS of 0–1 in just 40% of patients treated within 3 hours of stroke onset and 44% of patients treated at 3–4.5 hours.4 This is despite lesser stroke severity (National Institutes of Health Stroke Scale score: 10 in the SITS-ISTR cohort v 11.6 in the ECASS III placebo group), selective patient inclusion, and exclusion of patient data with protocol violations known to give worse outcomes.

Achieving a worse result than placebo is hardly evidence for safe and effective use of thrombolysis in normal clinical practice.

However, the Australian study presents the data differently, using an mRS of 0–2 and thereby concluding good outcomes in patients with greater disability than is the accepted good outcome measure.5 Rather than providing the actual data and the percentage of patients with good outcomes, a novel measure of odds ratio comparison with rest-of-world data is made.

Publishing data in the same format as for the full SITS-ISTR report would allay concerns of what may be unfavourable outcomes compared with clinical trial data. Patients deserve to be told what their likely prognosis will be in hospitals that are less experienced in stroke thrombolysis than The Alfred, where Waxman received world-class stroke care.