The latest results from ESPRIT (European/Australasian Stroke Prevention in Reversible Ischaemia Trial), published in the February 2007 issue of Lancet Neurology, confirm that the combination of dipyridamole plus aspirin is the treatment of choice for secondary stroke prevention in patients with stroke of arterial origin.1 The combination treatment showed a 24 percent relative risk reduction of the primary outcome event (death from all vascular causes, non-fatal stroke, non-fatal myocardial infarction, or major bleeding complication) compared with medium-intensity anticoagulation therapy.1

The benefit of prescribing dipyridamole plus aspirin to prevent new vascular events in patients who have had a stroke is clear, said Professor Ale Algra, University of Utrecht, Netherlands and lead investigator of the ESPRIT study. These patients are at high risk of having new vascular events that may be fatal, therefore effective antithrombotic therapy is vital. Earlier results from ESPRIT2 showed that a combination of dipyridamole plus aspirin is 20 percent better than aspirin alone, and our new results suggest that the combination is also better than treatment with anticoagulants.

Of key importance for the safety aspects of the antithrombotic treatment for secondary stroke prevention in ESPRIT was that the risk for major bleeding complications was at least 60 percent lower in patients receiving the combination of dipyridamole plus aspirin compared with anticoagulants. The patients in ESPRIT who were treated with dipyridamole plus aspirin had substantially fewer bleeding complications than those on anticoagulants," commented Professor Algra. For patients on anticoagulants, any potential beneficial effect in preventing ischaemic events was completely offset by an excess of major bleeding complications.

ESPRIT was an independent, international, investigator-led study that compared currently available oral anticoagulation (target international normalised ratio of 2.0 3.0), or the combination dipyridamole (400 mg daily) plus aspirin (30 - 325 mg daily), with aspirin alone in patients who had suffered a transient ischaemic attack (TIA) or a minor ischaemic stroke.3 The majority of patients received a free combination of aspirin and dipyridamole, the aspirin dosage varied from 30 to 325mg/day; up to 8 percent of the patients received the fixed-dose combination (200 mg extended release dipyridamole plus 25 mg aspirin twice daily, as marketed under Aggrenox and Asasantin). Although the study was open label, the assessment of outcome events was blinded. Earlier results from ESPRIT, published in The Lancet in May 2006, demonstrated a clear benefit for the combination treatment compared with aspirin alone in preventing vascular death, secondary stroke, myocardial infarction or major bleeding.2

International treatment guidelines currently recommend three treatment options for secondary stroke prevention: the combination of aspirin and diypridamole, aspirin alone and clopidogrel for stroke of arterial origin. Anticoagulants are mainly recommended for patients with stroke of cardiac origin. ESPRIT has demonstrated the benefit of the combination treatment over aspirin alone and currently available oral anticoagulants in patients with stroke of arterial origin.

Comparing the fixed-dose combination (Aggrenox, Asasantin) with clopidogrel is currently under investigation in PRoFESS (Prevention Regimen For Effectively avoiding Second Strokes), the largest stroke prevention study ever undertaken. The study closed enrolment in July 2006 and recruited more than 20,000 patients. First results are expected in 2008.

About ESPRIT

The European/Australasian Stroke Prevention in Reversible Ischaemia Trial (ESPRIT) was an investigator-led study designed to end the uncertainty about the relative effectiveness of three antithrombotic treatments after Transient Ischaemic Attack (TIA) or minor stroke of presumed arterial origin. Patients were randomised to three treatment arms: acetylsalicylic acid (ASA), ASA plus dypiridamole, and oral anticoagulation therapy within six months of a TIA or minor stroke of presumed arterial origin. The dipyridamole plus ASA versus ASA (aspirin) comparison is the subject of a publication in the The Lancet,2 while the dipyridamole plus ASA versus anticoagulation therapy comparison is published in Lancet Neurology1. The dose range of aspirin in ESPRIT was 30 - 325 mg/ day, with a median dosage of 75 mg/day. A total of 83 percent of the patients received extended-release dipyridamole, and up to 8 percent received the fixed-dose combination twice daily, which is marketed as Aggrenox or Asasantin. The ESPRIT trial used a composite endpoint which is not part of the Aggrenox (Asasantin) label. All patients were asked to return every six months for a consultation with their randomising physician or a trained trial nurse. Patients were followed up for a period of up to five years (mean length of follow-up was 3.5 years in the first part of ESPRIT and 4.6 years in the second part) with checks every six months. Baseline characteristics and prescribed dose of acetylsalicylic acid were similar in all treatment groups. None of the sponsors had a commercial interest in the outcome of the study.

About Aggrenox

Aggrenox is an antithrombotic 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 TIA. Marketed as Aggrenox and as Asasantin Retard is registered in over 50 countries worldwide.

About Stroke

Stroke is an acute event, which arises from disease of the blood vessels that supply blood to the brain. A stroke or cerebrovascular accident (CVA) causes sudden damage to the brain tissue and occurs when a blood vessel that is carrying oxygen and other nutrients to the brain bursts or is clogged by a blood clot or particulate material.4 The nerve cells are deprived of oxygen and die within minutes. Consequently, bodily functions under the control of those nerve cells will fail. The effects of a stroke are often permanent because the dead brain cells cannot be replaced.

About Transient Ischemic Attack (TIA)

TIA is often called a mini stroke with symptoms very similar to a full stroke including sudden weakness, numbness, clumsiness or pins and needles on one side of the body; sudden loss of, or blurred sight in one or both eyes; and slurred speech or difficulty finding words. Symptoms, however, subside within 24 hours. Without treatment a quarter of people suffering a TIA will go on to have a full-blown stroke within a few years.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 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. The ESPRIT Study Group. Medium intensity oral anticoagulants versus aspirin after cerebral ischaemia of arterial origin (ESPRIT): a randomised controlled trial. Lancet Neurology 2007;6:115-124

2. The ESPRIT Study Group. Aspirin plus dipyridamole versus aspirin alone after cerebral ischaemia of arterial origin (ESPRIT): randomised controlled trial. The Lancet 2006;367:1665-73

3. De Schryver EL. Design of ESPRIT: an international randomized trial for secondary prevention after non-disabling cerebral ischaemia of arterial origin. European/Australian Stroke Prevention in Reversible Ischaemia Trial (ESPRIT) group. Cerebrovasc Dis 2000;10:147-50

4. Heart and Stroke Facts. The American Stroke Association

5. Transient Ischaemic Attack Backgrounder. The Stroke Association UK

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