New JACC Analysis Details Cardiovascular Protective Benefits of Carvedilol In Heart Failure Patients

Philadelphia, March 9, 2007 -- Patients with heart failure who received the heart medication carvedilol suffered fewer heart attacks and strokes and were less likely to die of these and other vascular events than patients prescribed another beta blocker, metoprolol tartrate, according to a retrospective analysis of COMET (the Carvedilol or Metoprolol European Trial) published in the March 6th issue of The Journal of the American College of Cardiology.

Study investigators looked at whether the effects on vascular events contributed to the beneficial effect of carvedilol in the COMET trial, the longest and largest mortality trial comparing beta-blockers in heart failure patients. Among its key findings, the analysis documented that carvedilol reduced the risk of heart attacks, unstable angina, or stroke by 19% (p = .017). During the study, 106 of the 160 patients on metoprolol tartrate who had a nonfatal heart attack or stroke later died, while 61 of 124 patients on carvedilol who had a nonfatal heart attack or stroke later died.

COMET was a double-blind, randomized parallel group study designed to compare the effects of carvedilol with those of metoprolol tartrate on the risk of death and hospitalizations in patients with congestive heart failure. The study included more than 3,000 patients with heart failure primarily due to ischemic or dilated cardiomyopathy. Study participants were followed for an average of 58 months. According to COMET investigators, the study results suggested that the use of carvedilol in patients with heart failure extended median survival by 1.4 years.*

*The Carvedilol Or Metoprolol European Trial (COMET) compared carvedilol (target dose: 25 mg bid) to metoprolol tartrate (target dose: 50 mg bid). It is not known whether this formulation of metoprolol at any dose or this low dose of metoprolol in any formulation has any effect on survival or hospitalization in patients with heart failure. Metoprolol tartrate is not indicated in the United States for heart failure. COMET did not compare carvedilol to metoprolol succinate (Toprol-XL®*). The efficacy of carvedilol versus metoprolol succinate in heart failure has not been established in a head-to-head outcomes study. The target dose of metoprolol succinate in heart failure is 200 mg qd. Thus this trial extends the time over which carvedilol manifests benefits on survival in heart failure, but it is not evidence that carvedilol improves outcome over the formulation of metoprolol (Toprol-XL) with benefits in heart failure.

COMET data are based on a formulation of carvedilol that patients must take twice-a-day. The FDA recently approved a once-a-day formulation of carvedilol, which is bioequivalent to the twice-a-day version and delivers the appropriate amount of medicine over a 24-hour span. GSK anticipates making this once-a-day heart medication available to physicians and their patients later this month as Coreg CRTM (carvedilol phosphate) Extended-Release Capsules.    

COMET was jointly sponsored by GlaxoSmithKline and F. Hoffmann-La Roche.

About Carvedilol
Carvedilol is marketed by GlaxoSmithKline in the United States as Coreg (carvedilol) and COREG CR. It is the only beta-blocking agent FDA-approved to improve survival in patients with mild to severe heart failure. It also is the only beta-blocker the FDA has approved to reduce cardiovascular mortality in patients who had a heart attack that reduced how well the heart pumps.

COREG CR and COREG are approved to increase survival in patients with heart failure, reduce the risk of death in patients who had a heart attack that reduced how well the heart pumps, and treat hypertension, also known as high blood pressure.

Important Safety Information

It is important for patients to take their medicine every day as directed by their doctor or health care provider. If patients stop taking COREG CR or COREG suddenly, they could have chest pain and/or a heart attack. If the doctor decides that a patient should stop taking COREG CR or COREG, the doctor may slowly lower the dose over a period of time before stopping it completely.

Some common side effects associated with COREG CR and COREG include shortness of breath, a slow heartbeat, weight gain, fatigue, hypotension, dizziness, faintness, or runny nose/sore throat. People taking COREG CR or 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. Beta-blockers may mask the symptoms of an overactive thyroid or low blood sugar, or may alter blood sugar levels. People with diabetes should report any changes in blood sugar levels to their physician. Contact lens wearers may produce fewer tears or have dry eyes. As with any medicine, patients taking COREG CR or COREG should first tell their doctor what other medications they are taking. COREG CR and COREG should be taken with food.

There are some people who should not take COREG CR or COREG, including 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 CR or COREG. Other people who should not take COREG CR or COREG are those who are prone to asthma or other breathing problems, those with a very slow heartbeat or heart that skips a beat (irregular heartbeat) and those with liver problems.

About GlaxoSmithKline
GlaxoSmithKline, one of the world's leading research-based pharmaceutical and health care companies, is committed to improving the quality of human life by enabling people to do more, feel better and live longer.
For more information: heart medications and heart failure, visit Coreg.

Company information Web site address: http://www.gsk.com.
Cautionary statement regarding forward-looking statements
Under the safe harbor provisions of the US Private Securities Litigation Reform Act of 1995, the company cautions investors that any forward-looking statements or projections made by the company, including those made in this Announcement, are subject to risks and uncertainties that may cause actual results to differ materially from those projected. Factors that may affect the Group's operations are described under 'Risk Factors' in the 'Operating and Financial Review and Prospects' in the company's Annual Report 2005.

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