EACH YEAR FOR PATIENTS WITH ADVANCED HEART FAILURE

"The results of COPERNICUS, if applied appropriately, can have a greater impact on public health than most trials in cardiovascular medicine," said Milton Packer, M.D., Director, Heart Failure Center and Professor of Medicine, Columbia University College of Physicians and Surgeons in New York, NY and Chairman of the Steering Committee. "Over 300,000 patients in the United States die each year from heart failure. The results of the COPERNICUS trial showed that carvedilol has the potential to save as many as 50,000 lives annually, offering new hope for patients with the most advanced stage of heart failure."

Heart failure, a syndrome which occurs when the heart loses its ability to pump enough blood throughout the body, is a common disease that affects nearly 5 million Americans and is the only major cardiovascular disease on the rise. The fact that more people are surviving heart attacks is one contributing factor to this rise in incidence — it is estimated that 20 percent of the more than 1.1 million people who survive heart attacks go on to develop heart failure within six months. Approximately

400,000 to 700,000 new cases of heart failure are diagnosed each year and the number of deaths in the U.S. from this condition has more than doubled since 1979. Annual direct expenditures for heart failure

in the United States have been estimated at up to $40 billion, almost half of which is due to

hospitalization costs. Heart failure is responsible for more than 11 million physician office visits and over 3.5 million hospitalizations each year, making it the most frequent cause of hospitalization for people age 65 and older. Hospitalization risk is high in heart failure patients, and once hospitalized the patient’s risk for recurrent hospitalizations and death increases. Hospital readmission rates for heart failure approach 20 percent at one month and are as high as 47 percent after three to six months following the initial hospital stay.

"Heart failure is a serious public health problem, since patients with heart failure have greater disability and are hospitalized more often than patients with all forms of cancer combined," said Dr. Packer. "This study is critical because it shows that if physicians treated 1,000 patients like those in COPERNICUS with carvedilol for one year, they could save 70 lives."

Because of the impressive results with beta-blocking agents in large clinical trials, especially their effects on survival and hospitalizations, beta blocking agents are now recommended along with ACE inhibitors and diuretics as routine treatment for appropriate patients with mild to moderate heart failure. Despite this compelling evidence, beta blocking agents are dramatically under-utilized in the treatment of heart failure. It is estimated that less than 15 percent of patients with heart failure in the U.S. are receiving beta blockers.

To better understand the experience of beta blockade in treating heart failure patients in the usual care setting, as opposed to the more rigid clinical trial setting, the Coreg Heart Failure Registry, COHERE, has also been initiated and is currently enrolling patients. COHERE which aims to enroll 6,000 patients nationwide will be the first and largest prospective patient registry for an agent with beta blockade in heart failure treatment (Coreg). The experience with COHERE may provide additional impetus for more widespread use and acceptance of beta blocking agents in patients with heart failure.

The COPERNICUS study was conducted in over 300 medical centers in 21 countries and enrolled over 2,200 patients with advanced heart failure who had symptoms at rest or on minimal exertion, but not requiring intensive care unit care or intravenous treatments to support their heart’s function. In this controlled trial, half of the patients received Coreg and half received a placebo (sugar pill), which were

both added to the heart failure medications the patients were already taking (ACE inhibitors, diuretics,

and commonly digoxin). Patients were evaluated for an average of 10.5 months. Results of the study showed that treatment with Coreg decreased mortality by 35%. Additionally, Coreg treated patients showed:

• 31% reduction in all-cause mortality or heart failure hospitalizations
• 27% reduction in all-cause mortality or cardiovascular hospitalizations
• 24% reduction in all-cause mortality or hospitalizations for any reason

Coreg was very well tolerated. Statistically significantly more patients from the placebo group withdrew from the trial due to adverse reactions or other reasons than those from the carvedilol group.

Coreg, approved in May 1997, is the only drug with beta blocking properties approved in the U.S. for heart failure. It is presently indicated for the treatment of mild or moderate heart failure. Carvedilol is promoted in the United States as Coreg, by SmithKline Beecham Pharmaceuticals and Roche, and marketed in the rest of the world as Coreg, Dilatrend, and Kredex by Roche Pharmaceuticals. The COPERNICUS data will be filed with the FDA for their review and approval. SmithKline Beecham and Roche are seeking to broaden Coreg’s current indication to include patients with advanced heart failure.

Some common side effects associated with Coreg include shortness of breath, a slow heartbeat, weight gain, fatigue, dizziness or faintness. People taking Coreg who have any of these symptoms should call their doctor. Additionally, if patients experience fatigue or dizziness, they should sit or lie down and avoid driving or hazardous tasks. As with any medicine, there are some people who should not take Coreg. The people who should not take Coreg include those with severe heart failure who are hospitalized in the intensive care unit. Also, people who require certain intravenous medications that help support their circulation (inotropic medications) should not receive Coreg. Other people who should not take Coreg are those with asthma or other breathing problems, those with a very slow heartbeat or heart

that skips a beat (irregular heartbeat), those with liver disease and those who are allergic to Coreg. People with diabetes should report any changes in blood sugar levels to their physician. Contact lens wearers may produce less tears or have dry eyes. As with any medicine, patients taking Coreg should also first tell their doctor what other medications they are taking.

SmithKline Beecham–one of the world's leading healthcare companies -discovers, develops, manufactures and markets pharmaceuticals, vaccines, over-the-counter medicines and health-related consumer products. For company information, visit SmithKline Beecham on the World Wide Web at http://www.sb.com.

Contact: Megan Smith (212) 598-2810 212-598-2880