Results from SITS-MOST (Safe Implementation of Thrombolysis in Stroke - MOnitoring STudy) published in The Lancet today confirm that routine clinical thrombolysis therapy with Actilyse® (alteplase), the first and only approved treatment for acute ischaemic stroke, is as safe and effective as previously reported in randomised controlled trials when administered within three hours of onset of a stroke.1,2,3 This result is borne out across a wide range of centres, from those with specialist units to those with little previous experience.

"Time is brain and the earlier a patient is treated for stroke, the greater the benefit," according to Nils Wahlgren, Professor of Neurology at the Department of Neurology, Karolinska Institute, Stockholm, Sweden and Chairman of SITS International. "Randomised placebo-controlled trials have already shown that patients who experience a stroke and receive Actilyse thrombolysis treatment within three hours of onset of acute stroke are more likely to go on to survive and be capable of managing activities of daily living independently. To have these results corroborated by the largest-ever stroke registry, SITS-MOST, is tremendously important."

The SITS-MOST results show that mortality rates following Actilyse® treatment were even better in routine practice than had previously been seen in randomised controlled trials (11.3% vs. 17.3%).1 In addition, the incidence of symptomatic haemorrhages and of functional independence at three months were comparable to those seen in randomised controlled trials.1

While the efficacy of Actilyse® has been demonstrated in previous clinical trials,2,3 it is widely acknowledged that the safety and efficacy of a treatment may be different during routine clinical use than is seen during the structured controlled trials process. The authors conclude that SITS-MOST fulfilled the purpose outlined by the European Medicines Agency (EMEA) to show that intravenous stroke thrombolysis is safe in routine clinical use, even by centres with limited prior experience of thrombolytic therapy.

SITS-MOST is an open, prospective, observational safety monitoring study for centres practicing thrombolysis for acute stroke in Europe. Centres with a stroke unit, however sophisticated, could participate in the trial. The aim of SITS-MOST was to evaluate the safety of the routine use of Actilyse® in target populations.

SITS-MOST is the largest stroke registry worldwide, with 6483 patients recruited to the trial in 285 centres across 14 European countries.1 Professor Wahlgren said, "Although the recruitment to the SITS-MOST trial is beyond expectations, we need to encourage new stroke centres without previous experience to take up thrombolysis because less than two percent of all stroke patients in the EU actually receive treatment. This leads to unnecessary patient suffering and increased pressure on rehabilitation resources. SITS-MOST should be seen as a catalyst for the expansion of thrombolysis in stroke centres. SITS would like to see this rise to five percent by 2009."

In a further step, the European Cooperative Acute Stroke Study (ECASS) III is evaluating the efficacy and safety of using Actilyse® in patients with acute ischaemic stroke within a time-window of 3 to 4.5 hours.4 If it can be demonstrated that the therapeutic benefit and safety of Actilyse® treatment can be extended by an additional 1.5 hours after the onset of an acute stroke, many more European stroke patients can look forward to an improved outcome. Results of the ongoing ECASS III trial can be expected in 2008.4

About Actilyse

Stroke is a neurological emergency that can affect a specific area, or sometimes all of the brain. It can be caused by a burst blood vessel (haemorrhagic stroke) or occur when a vessel is obstructed by a blood clot (ischaemic stroke). Actilyse (alteplase) is the first and only treatment available for acute ischaemic stroke recommended by international guidelines as a first-line treatment.5,6,7 Actilyse??? is a clot-busting drug, which is injected directly into a vein. To achieve the best outcome, patients need to receive the medication within three hours of the onset of their stroke symptoms. Randomised placebo-controlled studies have shown that thrombolysis with Actilyse, administered within three hours of the onset of symptoms of ischaemic stroke, significantly improves clinical outcome at three months. Alteplase is an enzyme that occurs naturally in humans and causes blood clots to dissolve. Actilyse (alteplase) is registered in 87 countries across the world and marketed outside North America and Japan by Boehringer Ingelheim.

About SITS-MOST

Systematic reviews of randomised controlled trials indicate that treatment with thrombolytics is highly beneficial when given within three hours from onset of stroke symptoms. SITS-MOST (Safe Implementation of Thrombolysis in Stroke - MOnitoring STudy), the world??s largest stroke registry/network for acute stroke centres, has demonstrated that broad implementation of thrombolysis in acute stroke treatment is both as safe and as effective in routine clinical practice as it has been shown to be in randomised clinical trials. Data from SITS-MOST (n=6483) show that real-life treatment with Actilyse within three hours resulted in both improved mortality (11.3% vs. 17.3%) and safety (symptomatic intracerebral haemorrhage 7.3% vs. 8.6%) when compared to randomised controlled trials.1

SITS-MOST is embedded within the Safe Implementation of Thrombolysis in Stroke International Stroke Thrombolysis Register (SITS-ISTR), an internet-based, international monitoring registry for auditing the safety and efficacy of routine therapeutic use of thrombolysis in acute ischaemic stroke. The registry is available to clinicians in many countries worldwide except Japan and North America. Acute stroke treatment with thrombolysis is currently under-used with wide variations from country to country and region to region. Less than two percent of overall stroke patients in the EU currently receive thrombolysis (acutestroke).

About SITS (Safe Implementation of Thrombolysis in Stroke)

SITS is an academic-driven, non-profit, international collaborative initiative by the medical profession to certify excellence in acute stroke treatment. SITS started as an initiative by participants in the European-Australian randomised stroke thrombolysis studies (ECASS) and then spread to many centres in several countries. SITS initiated an internet-based interactive thrombolysis register, to serve as an instrument for clinical centres to follow their own treatment results and compare with other centres in their countries and in the collaborating countries. The register is now the technical basis for the International Stroke Thrombolysis Register (SITS-ISTR) and SITS Monitoring Study (SITS-MOST). In 2007, SITS plans to launch randomised trials on thrombectomy and other interventions. SITS continues to register patients for stroke thrombolysis with the aim to treat at least five percent of all stroke patients in 2009, using the approved treatment indications.

About ECASS III

The objective of the ECASS III study is to evaluate the efficacy and safety of intravenous thrombolysis using Actilyse in patients with acute ischaemic stroke and confirm that the thrombolytic therapy with Actilyse within a time-window of 3 to 4.5 hours after ischaemic stroke onset improves outcome compared to a placebo-treated control group. The study started in July 2003 and recruitment is ongoing. It is planned to include 800 patients into this trial in 15 European countries.

About Boehringer Ingelheim

The Boehringer Ingelheim group is one of the world??s 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 143 affiliates in 47 countries and almost 37,500 employees. Since it was founded in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing novel products of high therapeutic value for human and veterinary medicine.

In 2005, Boehringer Ingelheim posted net sales of 9.5 billion euro while spending almost one fifth of net sales in its largest business segment Prescription Medicines on research and development.

References:

1 Wahlgren N et al. Thrombolysis with alteplase for acute ischaemic stroke in the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST): an observational study. Lancet 2007;369:275-82

2 Hacke W et al. Association of outcome with early stroke treatment: pooled analysis of ATLANTIS, ECASS and NINDS rt-PA stroke trials. Lancet 2004;363:768-774

3 Hill, M.D. and A.M. Buchan, Thrombolysis for acute ischemic stroke: results of the Canadian Alteplase for Stroke Effectiveness Study. Cmaj, 2005. 172(10): p. 1307-12

4 ECASS 3 - The European Cooperative Acute Stroke Study ecass3

5 Strokeupdate. Stockholm: Karolinska Stroke Update Meeting, 2000. Consensus Statement on Thrombolysis: Available from: strokeupdate/ALLCURRENT/Consensus/Consensus_2000/2000.htm

6 Adams HP Jr, Adams RJ, Brott T et al. Guidelines for the early management of patients with ischaemic stroke: a scientific statement from the Stroke Council of the American Stroke Association. Stroke 2003; 34: 1056 83

7 The European Stroke Initiative Executive Committee and and European Stroke Initiative Writing Group: European stroke initiative recommendations for stroke management update 2003. Cerebrovasc Dis 2003; 16: 311 37

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