Cardiovascular study underway

The pharmaceutical company Boehringer Ingelheim has presented before the American Heart Association’s annual meeting its extensive cardiovascular trial program ONTARGET.

The program will investigate the additional potential of newer blood pressure-reducing medications called angiotensin II receptor blocker such as telmisartan.

Boehringer Ingelheim will also be conducting 10 additional cardiovascular studies.

"This trial program, the biggest ever undertaken by Boehringer Ingelheim, concerns one of the most challenging fields to study in the pharmaceutical industry," said Prof. Peter Sleight, one of the three chairmen of the ONTARGET trial program, from Oxford University in Great Britain.

"The results will provide us with a better understanding of the causes and mechanisms of cardiovascular diseases and the potential of angiotension II receptor blockers. Our aim is to provide patients with safe and effective treatments for life-threatening diseases," Sleight added.

ONTARGET is "Ongoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial." It will involve some 28,000 patients from about 700 sites worldwide for an observation period of up to five years.

Cardiovascular diseases are the most frequent cause of death in many countries and one of the biggest challenges in modern medicine.

According to the World Heart Federation, cardiovascular diseases were evaluated in 1991 as the leading cause of death worldwide, causing over 16.9 million deaths annually.

Preventive treatment options are essential in combating cardiovascular diseases. High blood pressure is one of the most important risk factors for cardiovascular diseases, causing heart attack, heart or kidney failure or stroke. Thus, physicians and the pharmaceutical industry have focused their efforts more consistently in this area.

Besides, newer blood pressure-reducing medications have been shown to have additional potentials to reduce cardiovascular diseases.

Two classes of drugs

Boehringer Ingelheim’s trial program is designed to investigate the preventive potential of a blood pressure-reducing class, called angiotensin II receptor blockers, in comparison with another important blood pressure lowering drug class, the ACE (angiotensin-converting enzyme) inhibitors. Each class will be studied alone and in combination therapy.

Both medications influence angiotensin II, a naturally occurring hormone which helps the body regulate blood pressure. Angiotensin II causes arteries to contract which increases blood pressure. However, both influence angiotensin II in very different ways.

Angiotensin II receptor blockers inhibit the binding of angiotensin II to the receptor that causes arteries to contract, leading to a relaxation of arteries, which allows the blood to flow more freely. This results in decreased blood pressure and better circulation. In contrast, ACE inhibitors prevent the formation of angiotensin II altogether.

Notable benefits can be seen from using angiotensin II receptor blockers, because they block only part of the effects of angiotensin II.

There are two kinds of angiotensin II receptors: type 1 and type 2. Angiotensin II receptor blockers inhibit type 1, but do not affect type 2. Angiotensin II binding to the type 2 receptor is thus able to continue protecting blood vessels from damage. When using ACE inhibitors, patients do not receive the vessel protecting benefits provided by angiotensin II.

The trials

Almost 29,000 patients will be included in the ONTARGET trial program and 6,000 more in the additional studies. Patients from all over the world, including most European countries, South Africa and North America, will be selected.

The additional studies, in the so-called PROTECTION program, will primarily focus on the elderly and diabetic patients, who may benefit mostly from the lower cardiovascular risk.

Initial results of this study program are expected in 2003 with the whole PROTECTION program completed by 2005.

Starting this month, another component of the ONTARGET trial program, a parallel group trial called TRANSCEND, will begin, concentrating on patients who are intolerant to ACE inhibitors.