CHICAGO, March 31 /PRNewswire/ -- The results of the landmark ONTARGET(TM) trial have demonstrated that MICARDIS(R) (telmisartan), a second-generation angiotensin II receptor blocker (ARB), is equally effective as the current standard, ramipril, in reducing the risk of cardiovascular death, myocardial infarction, stroke and hospitalization for congestive heart failure in a broad cross-section of high-risk cardiovascular patients with normal blood pressure or controlled high blood pressure, and resulted in fewer discontinuations.(1) These cardiovascular events occurred in 1,423 patients (16.7 percent) receiving telmisartan versus 1,412 patients (16.5 percent) receiving ramipril.(1) The relative risk (ratio of the probability of the event occurring in the telmisartan group versus the ramipril group) was 1.01, with a 95 percent CI of 0.94 - 1.09.
Telmisartan is now the only ARB to have demonstrated cardio and vascular risk reduction benefits beyond lowering blood pressure in this high-risk population;(1) these benefits may be attributed to the specific pharmacological properties and mode of action of the drug. Previously, in 2000, the HOPE trial showed that the cardiovascular risk for patients treated with the angiotensin-converting enzyme (ACE) inhibitor ramipril was reduced by approximately 20 percent compared with placebo.(2) This meant that every fifth serious cardiovascular event in a high risk group of patients was prevented.(2)
"The ONTARGET trial shows that telmisartan is a well-tolerated treatment in high-risk cardiovascular patients that is as effective as ramipril in preventing heart attacks, stroke and hospitalizations for heart failure and deaths," said Professor Salim Yusuf, lead investigator of the ONTARGET Trial Program and Director of the Population Health Research Institute at McMaster University, Hamilton, Canada. "The ONTARGET results have important implications for the management of patients with cardiovascular diseases."
In this trial, which was based on the HOPE study design, the benefits of telmisartan were demonstrated in a large group (8,542) of high-risk patients who were already receiving standard care such as statins to lower cholesterol, antiplatelet therapy, beta blockers and other antihypertensives.(3) Telmisartan treatment led to fewer discontinuations than treatment with ramipril, a widely used ACE inhibitor.(1) Although patients with an ACE inhibitor intolerance had been excluded from the trial, 360 (4.2 percent) patients in the ramipril treatment arm stopped their treatment because they experienced cough, a common ACE inhibitor side effect, versus only 93 (1.1 percent) patients in the telmisartan arm. Twenty-five patients stopped their treatment in the ramipril arm because of angioedema, versus only 10 in the telmisartan arm.(1) The incidence of hypotension was higher in the telmisartan arm (229 patients, 2.7 percent) versus the ramipril (149 patients, 1.7 percent) arm.(1)
"Boehringer Ingelheim is proud to have supported ONTARGET(TM), the largest cardiovascular outcomes trial of its kind and the first of a series of landmark clinical studies sponsored by our company. ONTARGET is just one example of Boehringer Ingelheim's leadership in trying to address the needs of people with cardiovascular disease," commented J. Martin Carroll, president and chief executive officer of Boehringer Ingelheim Pharmaceuticals, Inc. "We are committed to pursuing further research that evaluates ways to reduce the risk of damaging events in the heart, brain and other organs due to cardiovascular disease and to uncover new treatment strategies that may improve patient outcomes and care."
ONTARGET also studied the value of combining telmisartan with ramipril, to evaluate whether combining an ACE inhibitor and an ARB, i.e. the dual renin-angiotensin system (RAS) blockade, could offer even better risk reduction compared to single blockade, a key question for the clinical community. The results announced today indicate that there was no additional risk reduction benefit achieved and a higher discontinuation rate if telmisartan and ramipril are combined.(1)
About the ONTARGET(TM) Trial Program
The ONTARGET Trial Program is 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 encompasses two randomized, double-blind, multi-center international outcome trials: ONTARGET, the main trial with results reported today, and TRANSCEND(TM) (Telmisartan Randomized Assessment Study in ACE-intolerant subjects with cardiovascular disease), the parallel trial with results planned to be reported later in 2008.
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 compared the effectiveness of the ARB telmisartan to the ACE inhibitor ramipril in reducing the combined risk of cardiovascular death, myocardial infarction, stroke and hospitalization for congestive heart failure (CHF) in patients at risk. The study also compared the efficacy of the combination of the ARB telmisartan and the ACE inhibitor ramipril compared to ramipril alone in achieving the same combined endpoint.
The combined primary endpoint in the ONTARGET trial included cardiovascular death, non-fatal myocardial infarction, non-fatal stroke and hospitalization for congestive heart failure. In addition, a broad variety of secondary and tertiary endpoints were studied, including: newly diagnosed diabetes, cognitive decline/dementia, nephropathy, atrial fibrillation and left ventricular hypertrophy.
Treatment arms for the ONTARGET(TM) trial were telmisartan 80 mg, ramipril 10 mg and a combination therapy with telmisartan 80 mg and ramipril 10 mg. All treatments were applied in addition to standard care for high-risk cardiovascular patients.
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 consists 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 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 globally(4) and is responsible for one of every three deaths worldwide -- an estimated 17 million people per year.(5) CVD causes more deaths than cancer, chronic respiratory disease and diabetes combined.(6) By 2020, it is predicted that CVD will surpass infectious diseases to become the largest cause of death and disability worldwide.(7) 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.(8)
Boehringer Ingelheim and Cardiovascular Medicine
Boehringer Ingelheim continues its century-long history of innovation and commitment to continuing research to further understand cardiovascular disease -- the number one cause of death worldwide. Boehringer Ingelheim has introduced novel agents in the management of hypertension and treatment of secondary stroke and continues to invest in a comprehensive cardiovascular pipeline. The Company's cardiovascular medicine clinical trial program includes ONTARGET, PRoFESS, TRANSCEND and other studies involving more than 75,000 patients in more than 40 countries. These studies were designed to evaluate ways to reduce the risk of damaging events in the heart, brain and other organs due to cardiovascular disease and to uncover new treatment strategies that improve patient outcomes and care.
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 137 affiliates in 47 countries and approximately 38,400 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 2006, Boehringer Ingelheim posted net sales of US $13.3 billion (10.6 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(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 www.micardis.com for full Prescribing Information for MICARDIS.
References:
1 The ONTARGET Investigators. Telmisartan, ramipril, or both in patients at high risk for vascular events. N Engl J Med 2008; 358:1547-59.
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/TRANSCEND Investigators. Rationale, design, and baseline characteristics of 2 large, simple, randomized trials evaluating telmisartan, ramipril, and their combination in high-risk patients; The Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial/Telmisartan Randomized Assessment study In ACE Intolerant Subjects with Cardiovascular disease
4 Facts and Figures: World Health Report 2003. World Health Organization
5 The Atlas of Heart Disease and Stroke 2004 World Health Organization http://www.who.int/cardiovascular_diseases/resources/atlas/en/index.html
6 World Health Organization, Cardiovascular Disease http://www.who.int/cardiovascular_diseases/en/
7 Levenson J. et al. Reducing the global burden of cardiovascular disease: the role of risk factors. Preventative Cardiology, 2002; 5: 188-189.
8 Thom T et al. Heart disease and stroke statistics - 2006 update. Circulation. 2006; 113:e85-e151.
CONTACT: Anna Moses of Boehringer Ingelheim Pharmaceuticals, Inc.,
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Web site: http://us.boehringer-ingelheim.com/
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