Volume 194 - Issue 8
A population-based study of thrombolysis for acute stroke in South Australia
Author: Daniel M Fatovich
Med J Aust 2011; 194 (8): 431-432. || doi: 10.5694/j.1326-5377.2011.tb03049.x
Published online: 18 April 2011
Published online: 18 April 2011
To the Editor: The report by Leyden and colleagues highlights the value of examining the total experience of stroke thrombolysis in one population.1 The results are devastating: protocol violations in more than a third of cases (consistent with other reports of up to 50%2), and a 10% symptomatic intracranial haemorrhage (ICH) rate (representing a number needed to harm [NNH] of 10). As a clinician, I would be “gutted” if my treatment harmed every 10th patient. The 22% mortality at 3 months is consistent with real-world evidence that stroke thrombolysis increases mortality.3
Although the authors state that the rate of symptomatic ICH was not statistically significantly different to that in the National Institute of Neurological Disorders and Stroke (NINDS) study, an absolute increase of 3.6% (10% versus 6.4%) is clinically important to patients and their families. Presumably, this is largely related to the age protocol violations: 10 of 53 resulted in symptomatic haemorrhage (19%; NNH = 5), including seven cases of intracerebral haemorrhage and five deaths. In all, there were 39 cases of any ICH (25%; NNH = 4).
The article highlights that 54% of thrombolysis cases were not on the Safe Implementation of Thrombolysis in Stroke (SITS) registry. This result adds to the concerns of a selection bias in the SITS registry. As the authors point out, the sample size is small — too small, in my opinion, to draw any rigorous conclusions. This highlights that registry results should, at best, be hypothesis generating. However, it has also been highlighted that patients in the SITS International Stroke Thrombolysis Register do worse than those in the placebo group of the European Cooperative Acute Stroke Study III (ECASS III).4
The authors also refer to the ECASS III results, which contend that the time window for stroke thrombolysis should be extended to 4.5 hours. However, methodological and analytical flaws in this study, as well as the NINDS study, cast doubt on this statement.5 A recently published independent review of evidence on stroke thrombolysis concluded, “There is no consistent or proven benefit to thrombolytics”; it included all 11 clinical trials, of which nine had no benefit (with four of these causing harm).6 There are multiple examples in medicine where small studies suggest a benefit, but larger more definitive studies confirm otherwise.
Hence, it is very important to look at the totality of the evidence.7 While I agree with the authors that poor access to acute stroke units is deplorable, the real challenge is to define the role, if any, for thrombolysis in acute stroke. Pronouncements that we need to be thrombolysing more are a disservice to those who seek the truth.
References
- Leyden JM, Chong WK, Kleinig T, et al. A population-based study of thrombolysis for acute stroke in South Australia. Med J Aust 2011; 194: 111-115. 0_CBBFDIIG
- Katzan IL, Furlan AJ, Lloyd LE, et al. Use of tissue-type plasminogen activator for acute ischemic stroke: the Cleveland area experience. JAMA 2000; 283: 1151-1158. 0_CBBEJBBA
- Dubinsky R, Lai SM. Mortality of stroke patients treated with thrombolysis: analysis of nationwide inpatient sample. Neurology 2006; 66: 1742-1744. 0_i1095852
- Smith BJ. Thrombolysis for acute stroke in Australia [letter]. Med J Aust 2011; 194: 212. 0_i1095854
- Mosely M. Is tPA study intentionally deceptive? Emerg Med News 2009; 31: 5-6. 0_i1095856
- Newman D. Thrombolytics for acute ischemic stroke. The NNT Group, 2010. http://www.thennt.com/thrombolytics-for-stroke (accessed Mar 2011).
- Ioannidis JP. Why most published research findings are false. PLoS Med 2005; 2: e124. 0_i1095861