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.
SOURCE Boehringer Ingelheim Pharmaceuticals, Inc.