PRoFESS(R) Results Announced At XVII European Stroke Conference

Main Category: Stroke
Also Included In: Clinical Trials / Drug Trials;  Conferences;  Pharma Industry / Biotech Industry
Article Date: 15 May 2008 - 4:00 PST

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Results of the PRoFESS(R) (Prevention Regimen For Effectively avoiding Second Strokes) trial -- the world's largest clinical research study for secondary stroke prevention -- were presented at the XVII European Stroke Conference in Nice, France. In the study, recurrent stroke event rates for Aggrenox(R) and clopidogrel were similar (9.0% and 8.8%, respectively; HR 1.01, 95% CI 0.92-1.11). The study did not meet its primary endpoint of non-inferiority for AGGRENOX versus clopidogrel.(1)

In further exploratory analysis of the main secondary endpoint of the composite of stroke, myocardial infarction or vascular death, AGGRENOX and clopidogrel showed similar outcomes (13.1% versus 13.1%).(1)

In PRoFESS, the AGGRENOX arm had a higher number of hemorrhagic strokes compared to clopidogrel (0.8% and 0.4%, respectively) while ischemic stroke recurrences were less frequent in the AGGRENOX arm compared to the clopidogrel arm (7.7% and 7.9%, respectively).(1)

A post-hoc analysis showed comparable numbers of death and disabling strokes and a similar neurological outcome as measured by the modified Rankin Scale(2) at three months after the recurrent stroke and at the end of the PRoFESS trial between the two treatment arms.(1)

Major hemorrhagic events were observed more frequently in the AGGRENOX group compared with clopidogrel (4.1% versus 3.6%; HR 1.15, 95% CI 1.00-1.32). The benefit-risk ratio expressed as the combination of recurrent stroke and major hemorrhage was not significantly different between AGGRENOX and clopidogrel (11.7% and 11.4% respectively; HR 1.03, 95% CI 0.95-1.11).(1)

"Given the high prevalence of stroke and recurrent stroke in aging societies, physicians need a range of treatment options so they can offer patients a regimen tailored to their individual needs," said Professor Hans-Christoph Diener, MD, University of Essen, Germany, one of the three principal investigators of the study. "Landmark trials like PRoFESS will help clinicians make evidence-based treatment choices and ensure that patients receive optimal therapy for their condition."

The other regimen tested in PRoFESS investigated whether Micardis(R) tablets, combined with standard antiplatelet therapy, can further reduce the risk of recurrent stroke. At the end of the study, the results demonstrated that 8.7% of patients experienced recurrent stroke in the MICARDIS arm versus 9.2% in the placebo arm (p=0.23). Thus, the primary endpoint of superiority of MICARDIS versus placebo could not be statistically confirmed. The mean follow-up period was 2.5 years, and it is unclear whether a longer follow-up period would have yielded statistical significance. The PRoFESS results continue to support the safety and tolerability profile of MICARDIS.

"We are proud to have sponsored the PRoFESS study," said Dr. Thor Voigt, Senior Vice President, Medicine and Drug Regulatory Affairs, Boehringer Ingelheim Pharmaceuticals, Inc. "We set out to advance the understanding of strategies for recurrent stroke prevention and will continue to evaluate the PRoFESS data to help physicians make more informed treatment decisions."

About PRoFESS(R)

PRoFESS(R) (Prevention Regimen For Effectively avoiding Second Strokes) was designed to examine the effects of different prevention regimens on recurrent stroke, including the antiplatelet agent AGGRENOX versus clopidogrel and the efficacy of MICARDIS, an antihypertensive, compared to placebo in preventing recurrent stroke in the presence of background standard antihypertensive therapy. The trial was a randomized, double-blind, placebo-controlled clinical study that included 20,332 patients from 695 sites in 35 countries, with a four-year follow-up of patients.

PRoFESS is a collaborative effort between academia and the sponsor, Boehringer Ingelheim. Co-funders of the telmisartan arm of the study in selected countries are Bayer Schering Pharma and GlaxoSmithKline.

About Stroke

Stroke is the third-leading cause of death and a leading cause of chronic adult disability in the United States.(3) There are approximately 5.8 million stroke survivors in the United States,(4) and 21.5 percent of people who survive a first stroke or transient ischemic attack (TIA or "mini stroke"), will experience another episode within five years.(3)

About Aggrenox(R)

Aggrenox(R) (aspirin / extended-release dipyridamole) 25mg / 200mg capsules combine a low dose of aspirin and extended-release dipyridamole to reduce the risk of stroke in patients who have had transient ischemia of the brain or completed ischemic stroke due to thrombosis. AGGRENOX is the only combination drug that has shown superiority to low-dose aspirin in a head-to-head trial for the prevention of recurrent stroke with a comparable safety profile.

The most common adverse event with AGGRENOX was headache (38.2% vs 32.4% with placebo), which was more frequent at the onset of therapy but diminished over time. In ESPS 2, GI bleeding with AGGRENOX was comparable to aspirin (4.1% vs 3.2%) and the incidence of intracranial hemorrhage was nine (9) patients (0.6%) in the AGGRENOX group, six (6) patients (0.5%) in the extended-release dipyridamole group, six (6) patients (0.4%) in the aspirin group and seven (7) patients (0.4%) in the placebo group.

AGGRENOX contains aspirin. Patients who consume three or more alcoholic drinks every day should be counseled about the bleeding risks involved with chronic, heavy alcohol use while taking aspirin. Even low doses of aspirin can increase bleeding time, which can adversely affect patients with bleeding disorders. Patients with a history of active peptic ulcer disease should avoid using aspirin, which can cause gastric mucosal irritation and bleeding. AGGRENOX should be avoided in the third trimester of pregnancy.

For more information including complete Prescribing Information, please visit http://www.aggrenox.com.

About Micardis(R) (telmisartan)

Telmisartan is marketed in the United States by Boehringer Ingelheim as MICARDIS(R) tablets. MICARDIS is indicated for the treatment of hypertension.

USE IN PREGNANCY

When used in pregnancy during the second and third trimesters, drugs that act directly on the renin-angiotensin system can cause injury and even death to the developing fetus. When pregnancy is detected, MICARDIS tablets should be discontinued as soon as possible (see WARNINGS, Fetal/Neonatal Morbidity and Mortality).

Thiazides cross the placental barrier and appear in cord blood. There is a risk of fetal or neonatal jaundice, thrombocytopenia, and possibly other adverse reactions that have occurred in adults.

MICARDIS is contraindicated in patients who are hypersensitive to any of their components.

In patients with an activated renin-angiotensin system, such as volume- and/or salt-depleted patients (e.g., those receiving high doses of diuretics), symptomatic hypotension may occur after initiation of MICARDIS therapy. This condition should be corrected prior to administration of MICARDIS tablets, and treatment should start under close medical supervision.

The most common adverse events occurring with MICARDIS tablets monotherapy at a rate of 1% and greater than placebo, respectively, were: upper respiratory tract infection (URTI) (7%, 6%), back pain (3%, 1%), sinusitis (3%, 2%), diarrhea (3%, 2%), and pharyngitis (1%, 0%).

Please visit http://www.micardis.com for full Prescribing Information for MICARDIS.

Boehringer Ingelheim Pharmaceuticals, Inc.

Boehringer Ingelheim Pharmaceuticals, Inc., based in Ridgefield, CT, is the largest U.S. subsidiary of Boehringer Ingelheim Corporation (Ridgefield, CT) and a member of the Boehringer Ingelheim group of companies.

The Boehringer Ingelheim group is one of the world's 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 135 affiliates in 47 countries and approximately 39,800 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 2007, Boehringer Ingelheim posted net sales of US $15.0 billion (10.9 billion euro) while spending approximately one-fifth of net sales in its largest business segment, Prescription Medicines, on research and development.

For more information, please visit http://us.boehringer-ingelheim.com.

References

(1) Sacco R, et al. European Stroke Conference, Nice, France, 14 May 2008.

(2) Modified Rankin Scale. Internet Stroke Center. Available at http://www.strokecenter.org/trials/scales/rankin.html Accessed 4 May 2008

(3) American Heart Association. Heart Disease and Stroke Statistics: 2008 Update. Found at: http://www.circ.ahajournals.org/cgi/reprint/CIRCULATIONAHA.107.187998v1.

(4) American Heart Association/American Stroke Association Heart Disease and Stroke Statistics

Boehringer Ingelheim Pharmaceuticals, Inc.
http://us.boehringer-ingelheim.com