Intravenous thrombolysis for acute ischaemic stroke: from randomised clinical trials to daily practice

In the Netherlands, as in most Western countries, stroke is a major contributor to the total burden of disease, with an estimated 39,600 hospital admissions, 9,000 deaths, and approximately 241,600 people living with the consequences of a stroke in 2009.1 Fortunately, improvements are observed, stroke mortality is declining; due to a both declines in incidence of stroke as well as in case fatality.2,3 New treatments like thrombolysis for acute ischaemic stroke are highly effective, but the main cause of increased survival rates after stroke is a better coordination of care, through widespread implementation of stroke units.4,5 Thrombolysis refers to the breakdown of blood clots by stimulating fibrinolysis. In 1995 a large American study on the effectiveness of thrombolysis with intravenous alteplase (recombinant tissue plasminogen activator, rTPA) for patients with acute ischaemic stroke was published. Patients treated with intravenous alteplase had a better functional outcome at three months.6 However two European trials (MAST I and MAST E) had unfavourable results and the ECASS I had inconclusive results.7-9 The higher complication rate was attributed to a too high dose of thrombolytic and the lack of improvement was attributed to the extended time window of 6 hours. In 1998 the ECASS II trial was published, but it also showed inconclusive results.10 A few years later in 2000 the Cochrane Review (including all the trials mentioned above) was published and showed that thrombolytic therapy appears to result in a significant net reduction in the proportion of dependency or death. The relative reduction in risk of poor outcome, defined as a modified Rankin Score >2, was 17.5% (95% CI: 7 to 26%).11 The scepticism about treatment with rTPA gradually declined. Steadily but slowly, more and more hospitals started to treat acute ischaemic stroke patients with thrombolysis, but in daily practice, several circumstances and causes put a constraint on the number of patients who could be treated, the most important cause being the narrow time window for treatment. Taking that narrow time window into account, it was estimated that up to 24% of the stroke patients presenting at the emergency care might be eligible for thrombolysis. 12 In 2002-2003 however, the rate of thrombolysis in Dutch hospitals varied between 1% and 8%, with a few exceptions.13 Clearly, improvements could be made. In addition, concern about bleeding complications remained an issue. A European license for alteplase was provided on the condition that safety and effectiveness would be monitored in a European registry. This resulted in the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST).

• View at Worldcat

Free Full Text ( Final Version , 2mb )