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TRANSCEND™ Trial Results Presented at European Society of Cardiology Congress and Published in The Lancet

- Landmark ARB trial investigated Micardis® (telmisartan) against placebo in reducing the composite endpoint of cardiovascular death, myocardial infarction, stroke and hospitalization for congestive heart failure in ACE inhibitor intolerant high-risk patients receiving current standard of care -

Ridgefield, CT, August 31, 2008 —The primary results of the TRANSCEND™* trial demonstrated that treatment with MICARDIS® (telmisartan) 80mg in patients receiving current standard of care resulted in an 8% reduction in the composite endpoint of cardiovascular death, myocardial infarction, stroke and hospitalization for congestive heart failure.  This reduction was not statistically significant (p=0.216; HR 0.92) compared to patients receiving placebo in addition to current standard of care.¹  Results of the main secondary endpoint of TRANSCEND as pre-specified in the statistical plan demonstrated that telmisartan significantly reduced the risk of cardiovascular death, myocardial infarction and stroke in high-risk cardiovascular patients by 13% compared with those patients already receiving current standard of care (p=0.048).¹ This risk reduction was achieved despite a high proportion of patients receiving proven therapies such as statins, anti-platelet agents or beta blockers. The main secondary endpoint of TRANSCEND mirrors the primary endpoint of the landmark HOPE trial.² A post-hoc analysis requested by The Lancet to adjust for multiplicity and overlap with primary endpoint showed a p-value of 0.068.¹ The results were presented today at the annual meeting of the European Society of Cardiology in Munich, Germany and published in The Lancet.

In high-risk patients who cannot tolerate an angiotensin-converting enzyme (ACE) inhibitor, the TRANSCEND trial was designed to investigate potential cardiovascular risk reduction benefits using the second-generation angiotensin II receptor blocker (ARB) telmisartan. Telmisartan was compared to placebo on top of standard therapy (including anti-hypertensives, anti-platelet therapy and statins).

The TRANSCEND trial was part of the ONTARGET™ Trial Program, the largest clinical trial ever undertaken with an ARB, involving more than 31,000 high-risk cardiovascular patients with either normal or controlled blood pressure. The ONTARGET Trial Program was based on the design of the landmark HOPE trial and encompassed two randomized, double-blind, multi-center international outcome trials:  ONTARGET**, the main trial with results reported in March 2008,³ and TRANSCEND, the parallel trial.

“Previously, the ONTARGET™ trial showed that telmisartan was as effective as the ACE inhibitor ramipril in reducing the risk of cardio- and cerebrovascular events, but with a lower rate of discontinuations.  For high-risk patients who cannot tolerate an ACE inhibitor, the TRANSCEND™ results could represent an important step forward,” said Michael Weber, M.D., professor of medicine at the State University of New York, Downstate College of Medicine. 

It was also published that all cardiovascular hospitalizations were significantly reduced with telmisartan (894 vs. 980; p=0.025). Therapy with telmisartan was well tolerated and showed a trend toward a lower rate of discontinuation (640 patients discontinued taking telmisartan vs. 707 taking placebo, p=0.051).¹ The most frequently reported reasons for discontinuation were hypotensive symptoms, syncope, cough, diarrhea, angioedema and renal abnormalities.

TRANSCEND included 5,926 patients from 40 countries who were at high risk for cardiovascular disease (patients older than 55 years, who have had myocardial infarction, peripheral arterial occlusive disease, stroke or transient ischaemic attacks or suffer from diabetes mellitus and additional risk factors) and intolerant to widely-prescribed ACE inhibitors. Patients in the trial were randomized to treatment with telmisartan 80mg/day or placebo. 

It has been reported in medical literature that the incidence of patients with hypertension who are intolerant to ACE inhibitors ranges between 10-39%,^4-6   which often leads to discontinuation of treatment leaving patients unprotected. Side effects associated with ACE inhibitors include intolerable cough and rare, but potentially life threatening, angioedema.^4-6

“The landmark ONTARGET and TRANSCEND trials have contributed significant and important clinical information to the cardiovascular community and could help uncover new treatment strategies to improve patient outcomes and care,” said Thor Voigt, M.D., senior vice president, Medicine and Drug Regulatory Affairs, Boehringer Ingelheim Pharmaceuticals, Inc.

About the ONTARGET Trial Program
The ONTARGET Trial Program was the largest clinical trial ever undertaken with an ARB, involving more than 31,000 high-risk cardiovascular patients with either normal or controlled blood pressure.  The ONTARGET Trial Program encompassed two randomized, double-blind, multi-center international outcome trials: ONTARGET, the main trial, and TRANSCEND, the parallel trial.

ONTARGET evaluated more than 25,600 high-risk cardiovascular patients with normal blood pressure or controlled high blood pressure and a history of a broad range of cardiovascular diseases.  The study found that telmisartan is equally effective as the current standard, ramipril, in reducing the risk of cardiovascular death, myocardial infarction, stroke and hospitalization for congestive heart failure, and resulted in fewer discontinuations.  Telmisartan is now the only ARB to have demonstrated cardio and vascular risk reduction benefits beyond lowering blood pressure in this high-risk population; these benefits may be attributed to the specific pharmacological properties and mode of action of the drug.²

The combined primary endpoint in both the TRANSCEND and ONTARGET trials included cardiovascular death, non-fatal myocardial infarction, non-fatal stroke and hospitalization for congestive heart failure.  The secondary endpoint in the TRANSCEND™ trial was the effect of telmisartan treatment on the incidence of newly diagnosed congestive heart failure, revascularization procedures, newly diagnosed diabetes mellitus, cognitive decline and dementia and new onset of atrial fibrillation.

More than 700 sites throughout Asia, Australia, New Zealand, Europe, North/South America and South Africa participated in the ONTARGET™ Trial Program.  The ONTARGET Steering Committee consisted of scientists from McMaster University in Ontario, Canada; Oxford University in Oxford, England; the University of Auckland in Auckland, New Zealand; and Boehringer Ingelheim.

The ONTARGET Trial Program was investigational and was conducted to expand scientific knowledge of telmisartan.  Note that the trial included treatment for conditions outside the approved indication for telmisartan.

About Cardiovascular Disease
Cardiovascular disease (CVD) is the number one cause of death and disability globally⁷ and is responsible for one of every three deaths worldwide – an estimated 17 million people per year.⁸  CVD causes more deaths than cancer, chronic respiratory disease and diabetes combined.⁹ By 2020, it is predicted that CVD will surpass infectious diseases to become the largest cause of death and disability worldwide.¹⁰ It is also contributes significantly to the escalating costs of health care.  In 2006, the cost of CVD in the U.S. was estimated at $403.1 billion.¹¹

About 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.

About Micardis^® (telmisartan)
Telmisartan is marketed in the United States by Boehringer Ingelheim as MICARDIS^® 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 www.micardis.com for full Prescribing Information for MICARDIS.

 

Contact:

Anna Moses
Public Relations
Boehringer Ingelheim Pharmaceuticals, Inc.
Phone: (203) 798-4638
anna.moses@boehringer-ingelheim.com

 

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References

1. Yusuf, S et al. Effects of the angiotensin-receptor blocker telmisartan on cardiovascular events in high-risk patients intolerant to angiotensin-converting enzyme inhibitors: a randomized controlled trial. The Lancet. Published Online, August 31, 2008; DOI:10.1016/S0140-6736(08)61242-8.
2. The Heart Outcomes Prevention Evaluation Study Investigators. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. N Engl J Med 2000; 342:145-53.
3. The ONTARGET investigators. Telmisartan, ramipril, or both in patients at high risk for vascular events. N Eng J Med 2008; 358(15):1547-59.
4. Israili ZH, Hall WD. Cough and angioedema associated with angiotensin-converting enzyme inhibitor therapy. A review of the literature and pathophysiology. Ann Intern Med 1992; 117(3):234-42.
5. Matchar DB, et al. Systematic Review: Comparative effectiveness of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers for treating essential hypertension. Ann Intern Med 2008; 148:16-29.
6. Macaulay TE, Dunn SP. Cross-reactivity of ACE-inhibitor-induced angioedema with ARBs. US Pharmacist 2007; 32 (2).
7. Facts and Figures: World Health Report 2003. World Health Organization
8. The Atlas of Heart Disease and Stroke 2004 World Health Organization http://www.who.int/cardiovascular_diseases/resources/atlas/en/index.html
9. World Health Organization, Cardiovascular Disease http://www.who.int/cardiovascular_diseases/en/
10. Levenson J. et al. Reducing the global burden of cardiovascular disease: the role of risk factors. Preventative Cardiology, 2002; 5: 188-189.
11. Thom T et al. Heart disease and stroke statistics – 2006 update. Circulation 2006; 113:e85-e151.

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