Early Administration of Aggrenox(R) is Effective and Safe After Acute Ischaemic Stroke or TIA

INGELHEIM, Germany -

- For Healthcare Media Outside the U.S.A., Canada, and Japan

Early secondary prevention with Aggrenox(R) (extended-release dipyridamole [200 mg] plus ASA* [25mg]) is at least as effective and safe as initial treatment with ASA 100 mg alone after an ischaemic stroke or transient ischaemic attack (TIA). Results from the EARLY[1] study, presented for the first time at the 13th Congress of the European Federation of Neurological Societies in Florence on 15 September 2009, showed that while functional outcome at 3 months was similar between the two treatment groups there were numerically fewer recurrent ischaemic events in patients who received Aggrenox(R) from the first day after their ischaemic event compared to those patients who received ASA as initial therapy.

“Guidelines recommend administration of ASA as the gold standard for early secondary prevention after ischaemic stroke,” explained Professor Reinhard Dengler, Director of the Neurology Clinic at the Hannover Medical School and Coordinating Investigator of EARLY. “We now have scientifically-based experience with early administration of extended-release dipyridamole plus ASA. EARLY is the first study to have investigated this in a prospective manner.”

EARLY involved more than 250 investigators from 46 stroke units across Germany, who enrolled and treated 543 patients within 24 hours of an ischaemic event. The study is based on the PROBE (prospective, randomized, open-label to treatment blinded to endpoint) design and had two treatment arms:

- 283 patients received Aggrenox(R) (extended-release dipyridamole [200 mg] plus ASA [25mg]) twice daily from day 1 to day 90 after an ischaemic stroke or TIA - 260 patients received ASA 100 mg once daily between days one and seven, followed by Aggrenox(R) (extended-release dipyridamole [200 mg] plus ASA [25mg]) twice daily between days 8 and 90.

The primary efficacy outcome (severity of disability) was measured 90 days after the ischaemic event based on a blinded telephone assessment using the Modified Rankin Scale (mRS). After 90 days, 56.4 per cent of patients who received Aggrenox(R) treatment from Day 1 had little or no disability (mRS 0-1) compared with 52.4 per cent of patients in the ASA initial therapy group (odds ratio 0.96; 95% CI: 0.65.-1.42; p = 0.83).

For the combined secondary outcome of vascular and non-vascular death, non-fatal stroke, TIA, non-fatal myocardial infarction and bleeding complications, EARLY showed that there were numerically fewer events with early administration of Aggrenox(R) compared with ASA (hazard ratio [HR]: 0.7; 95% CI: 0.41-1.19; p = 0.19). The relative risk of a relevant outcome was 30 per cent lower in the early Aggrenox(R) therapy group (28 patients; 9.9 per cent) than in the ASA initial therapy group (38 patients; 14.6 per cent). The difference in the occurrence of non-fatal stroke and TIA was particularly marked, with 32 events (12.3 per cent) in the ASA initial therapy group compared with 20 (7.1 per cent) in the early Aggrenox(R) therapy group (HR: 0.63; 95% CI: 0.34-1.14; p = 0.12). Although not statistically significant, these data in favour of initial therapy with Aggrenox(R) are consistent with the results of the ESPS-2[2] and ESPRIT[3] studies, which showed treatment with the extended-release dipyridamole /ASA combination to be safe and superior to treatment with ASA alone.

“Although the trend in favour of early initiation of Aggrenox(R) is not significant, we see biological pointers which indicate a benefit,” explained Prof. Dengler.

Safety data from EARLY indicate that initial therapy with Aggrenox(R) was as safe as initial treatment with ASA, with respect to serious adverse events and deaths. In patients who received early initiation with Aggrenox(R) there was an increased incidence of headache and gastrointestinal complaints

“EARLY has shown that early initiation of therapy with extended-release dipyridamole plus ASA is at least as safe and effective as early initiation of treatment with ASA alone,” said Prof. Dengler.

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This release is from Boehringer Ingelheim Corporate Headquarters in Germany. Please be aware that there may be national differences between countries regarding specific medical information, including licensed uses. Please take account of this when referring to the information provided in this document. This press release is not intended for distribution within the U.S.A.

Notes to Editor:

*ASA = acetylsalicylic acid (Aspirin(R))

Modified Rankin Scale

The Modified Rankin Scale is a numerical functional assessment scale used to rank levels of disability after stroke. Patients receive a score between 0 and 6, where 0 represents no symptoms at all and higher scores represent increasingly severe disability.[4]

About ESPS-2

In the ESPS-2 study it was shown that the combination of low dose aspirin plus extended-release dipyridamole (marketed as Aggrenox(R) and Asasantin Retard(R)) reduced the risk of recurrent stroke by 37 precent compared to placebo. Stroke risk was reduced by 18.1% in the aspirin-alone group.[2]

About ESPRIT

The ESPRIT trial compared a combination of ASA and dipyridamole with ASA alone. The majority of patients on the combination received a free combination of ASA and extended-release dipyridamole (200mg twice daily); 8 percent of the patients received the fixed-dose combination (200mg extended-release dipyridamole plus 25 mg ASA twice daily, as marketed as Aggrenox(R) and Asasantin(R) Retard). Free ASA dosages varied from 30 to 325mg/day.[3]

About Aggrenox(R)

Aggrenox(R) (marketed as Aggrenox(R) and as Asasantin(R) Retard) is an antiplatelet agent that combines extended release dipyridamole and ASA. A product of Boehringer Ingelheim’s research and development, it is indicated for the prevention of recurrent stroke and transient ischaemic attack (TIA).[5]

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 138 affiliates in 47 countries and 41,300 employees. Since it was founded in 1885, the independent, family-owned company has been committed to researching, developing, manufacturing and marketing novel products of high therapeutic value for human and veterinary medicine.

In 2008, Boehringer Ingelheim posted net sales of 11.6 billion euro while spending one fifth of net sales in its largest business segment Prescription Medicines on research and development.

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References 1. Dengler R et al. Early treatment of Aspirin and Extended-Release Dipyridamole versus Aspirin alone for treatment of Minor Ischaemic Stroke within 24 hour of stroke-onset (EARLY-Trial): a randomised, open-labelled, blinded-endpoint trial. Eur J Neurol 2009 (Suppl). 2. Diener HC et al. European Stroke Prevention Study 2: Efficacy and Safety data. J Neurol Sci 1997: 151 (Suppl); 1-77 3. ESPRIT Study Group. Aspirin plus dipyridamole versus aspirin alone after cerebral ischaemia of arterial origin (ESPRIT). Lancet 2006: 367; 1665-1673 4. Modified Rankin Scale. Internet Stroke Center. Available at www.strokecenter.org/trials/scales/rankin.html Accessed 7 September 2009 5. Summary of product characteristics. Asasantin Retard(R). Electronic medicines compendium. emc.medicines.org.uk Accessed 7 September 2009

Source: Boehringer Ingelheim

Contact: John Pugh, Corporate Division Communications, Boehringer Ingelheim GmbH, 55216 Ingelheim/Germany, E-mail: press at boehringer-ingelheim.com