Boehringer Ingelheim GmbH
Corporate Division Communications
Dr Reinhard Malin
Results of 25,620 patient study ONTARGET (ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial) presented today at the 57th Annual Scientific Session of the American College of Cardiology1
For medical media, outside the US only
Ingelheim, Germany, 31 March, 2008 - The results of the landmark ONTARGET Trial have proven that telmisartan, brand name Micardis, a modern angiotensin II receptor blocker (ARB), is as protective as the current gold standard, ramipril, in reducing the risk of cardiovascular death, myocardial infarction, stroke, and hospitalisation for congestive heart failure in a broad cross-section of high-risk cardiovascular patients and with better tolerability.1 These cardiovascular events occurred in 16.66% of patients receiving telmisartan versus 16.46% of patients 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% CI of 0.94 -1.09.
In 2000, the HOPE trial showed that the cardiovascular risk for patients treated with ramipril is reduced by approximately 20% compared with placebo.2 This meant that every fifth serious cardiovascular event in a high risk group of patients was prevented. A similar effect can now be attributed to telmisartan. The 25,620 high-risk patients in the ONTARGET Trial were already receiving standard care such as statins to lower cholesterol, antiplatelet therapy, betablockers and other antihypertensives.3 Telmisartan was also shown to be significantly better tolerated than ramipril, a widely used angiotensin converting enzyme inhibitor (ACE), with respect to typical ACE-inhibitor side-effects.1 Although patients with an ACE-inhibitor intolerance had been excluded from the trial, 360 patients in the ramipril treatment arm stopped their treatment because they experienced cough versus only 93 patients in the telmisartan arm. 25 patients stopped their treatment in the ramipril arm because of angioneurotic edema, versus only 10 in the telmisartan arm.1
The ONTARGET data also show that telmisartan is associated with a higher treatment compliance.1 Besides efficacy, tolerability and compliance are also important factors to consider as they are crucial for effective long-term treatment for the prevention of serious cardiovascular events.
Telmisartan is now the only angiotensin II receptor blocker (ARB) to have proven cardio & vascular protective benefits beyond blood pressure reduction in this high-risk population.1 Until now, only the ACE-inhibitor ramipril had shown these protective effects.2
ONTARGET also studied the value of combining telmisartan with ramipril, to answer a key question for the clinical community - does combining an ACE inhibitor and an ARB, i.e. the dual renin-angiotensin system (RAS) blockade, offer even better protection compared to single blockade? The results announced today indicate that there is no additional protective benefit achieved for the overall patient population, if ramipril and telmisartan are combined.
Implications of the ONTARGET Trial
"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, hospitalisations for heart failure and deaths", said Professor Salim Yusuf, lead investigator of the ONTARGET Trial Programme 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. We now have a new treatment option for high-risk patients which is effective and better tolerated."
Largest ARB outcome trial ever
ONTARGET is a randomised, double-blind clinical trial, which evaluated 25,620 high-risk cardiovascular patients with normal or controlled blood pressure over an observation period of up to 6 years.
"We are proud to have started ONTARGET, the largest outcome cardiovascular trial ever undertaken with an ARB. It included high-risk cardiovascular patients with a history of coronary heart disease, stroke, transient ischaemic attack, peripheral vascular disease or diabetes with target organ damage. The trial has an extremely robust data base that will enable the medical community to answer questions where no scientific proof was available before. With 99.8% of patients followed over these years, this is one of the best managed landmark trials ever. We owe this excellent management of the trial to the investigators in over 700 centres across 40 countries led by Professor Salim Yusuf and his team at McMaster University, Hamilton, Canada." said Dr Andreas Barner, Member of the Board of Managing Directors of Boehringer Ingelheim, responsible for Research, Development and Medicine.
Benefits related to exceptional properties and structure of telmisartan
Further evidence of the exceptional properties of telmisartan has already been seen in previous trials. In 2007, the AMADEO trial showed that telmisartan achieved significantly greater reduction in proteinuria compared with the ARB losartan beyond blood pressure reduction effects, demonstrating the potential for renal protection with telmisartan in diabetic patients.4 In addition, in 2006 the PRISMA trials in hypertensive patients demonstrated that telmisartan achieved more powerful blood pressure reductions compared with the ACE-inhibitor ramipril.5,6
"The benefits of telmisartan seen in ONTARGET and previous trials may be attributed to the specific pharmacological properties and mode of action of telmisartan, including long half-life, large volume of distribution, high cell penetration and a selective AT1 blockade. ONTARGET now provides the evidence that the properties of telmisartan translate into relevant clinical outcomes", commented Professor Michael Bhm, Director of the Department of Cardiology, Universittsklinik des Saarlandes, Homburg, Germany and National Coordinator of the ONTARGET Trial in Germany.
Addressing the world`s largest healthcare burden
Cardiovascular disease (CVD) is the leading cause of death worldwide, causing over 17.5 million deaths per year.7 7.6 million people die from a heart attack and 5.7 million die from a stroke every year.7 Global deaths from CVD are predicted to reach approximately 25 million by 2020.8 CVD is also currently a leading cause of disability, and is predicted to be the largest cause of disability worldwide by 2020.8 A major stroke is viewed by more than half of those at risk as being worse than death.9
Please be advised
This release is from Boehringer Ingelheim Corporate Headquarters in Germany. Please be aware that there may be national differences between countries regarding specific medical information, including licensed uses. Please take account of this when referring to the information provided in this document. This press release is not intended for distribution within the U.S.A.
Notes to editors
The ONTARGET Trial Programme consists of two randomised, double-blind, multicentre international trials: the principle trial, ONTARGET which reports its results today, and a parallel trial TRANSCEND (Telmisartan Randomized AssessmeNt Study in ACE-i INtolerant subjects with cardiovascular Disease), which is planned to be reported later in the year.3
The treatment arms for the ONTARGET Trial were telmisartan 80mg, ramipril 10mg, and combination therapy with telmisartan 80mg and ramipril 10mg. In the TRANSCEND trial the treatment arms are telmisartan 80mg or placebo - both on top of standard blood pressure care, not including an ACE or another ARB.3
Patients enrolled in the ONTARGET Trial Programme were aged ≥ 55 years, had a history of coronary artery disease, stroke or recent (> 7 days, < I year) transient ischaemic attack, peripheral vascular disease, or diabetes mellitus with target-organ damage such as microalbuminuria, ankle-brachial index < 0.8, or left ventricular hypertrophy.3
The ONTARGET Trial had a four-fold composite endpoint:
hospitalisation for heart failure.
Patients intolerant to ACEs were not eligible for the ONTARGET study. Intolerance to ACE was a requirement for enrolment into TRANSCEND.
About telmisartan (Micardis/Kinzal/Pritor)
Telmisartan is a member of the angiotensin II receptor blocker (ARB) class and approved for the treatment of mild to moderate hypertension. It is being investigated in the most ambitious and far-reaching research programme ever conducted with an ARB. In the ongoing clinical trial programmes ONTARGET , PROTECTION and PRoFESS, over 58,000 patients have been enrolled to investigate the cardiovascular protective effects of telmisartan.
Telmisartan was discovered and developed by Boehringer Ingelheim. Under the trademarks Micardis and MicardisPlus (combination with hydrochlorothiazide) the company markets telmisartan in 84 countries around the world, including the USA, Japan and European countries. Telmisartan is marketed in cooperation with Astellas Pharma Inc. in Japan, Bayer HealthCare in Europe and GlaxoSmithKline in selected markets.
Astellas Pharma Inc. co-promotes telmisartan under the trademark Micardis, Bayer HealthCare promotes telmisartan under the brand names Kinzalmono, Kinzalkomb (combination with hydrochlorothiazide), and Pritor® and PritorPlus in markets across Europe. Pritor and PritorPlus is also marketed by GlaxoSmithKline in selected markets.
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 137 affiliates in 47 countries and 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 10.6 billion euro while spending one fifth of net sales in its largest business segment, Prescription Medicines, on research and development. 2007 business figures will be available from 8 April 2008 onwards.
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1.The ONTARGET Investigators. Telmisartan, ramipril, or both in patients at high risk for vascular events. N Eng J Med. Published online 31 Mar 2008.
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 (ONTARGET/TRANSCEND) trials Am Heart J 2004; 148(1):52-61.
4. Bakris G, et al. Influence of glycemic control on proteinuria in patients with type 2 diabetes and overt nephropathy and hypertension: results of the AMADEO trial. 67th Sci Sess of the American Diabetes Association (ADA), Chicago, 22 - 26 Jun 2007 (Poster) 2007.
5. Williams B, et al. The prospective, randomised investigation of the safety and efficacy of telmisartan versus ramipril using ambulatory blood pressure monitoring (PRISMAI). J Hypertens 2006; 24:193-200.
6. Lacourcière Y, et al. A multicenter, 14-weeks study of telmisartan and ramipril in patients with mild to moderate hypertension using ambulatory blood pressure monitoring. Am J Hypertens 2006; 19:104-12
7. World Health Organization, Fact Sheet 317: Cardiovascular Diseases February 2007. http://www.who.int/mediacentre/factsheets/fs317/en/index.html (Accessed March 2008)
8. Murray CJL, Lopez AD. eds. The Global Burden of Disease: A Comprehensive Assessment of Mortality and Disability from Diseases, Injuries, and Risk Factors in 1990 and Projected to 2020. Cambridge; Harvard University Press 2001.
9. Primary Prevention of Ischemic Stroke. A Guideline From the American Heart Association/American Stroke Association Stroke Council. Stroke 2006; 37:1583-1633.