Columbia University Medical Center

Copernicus Trial Shows Major Mortality Reduction With Carvedilol In Advanced Heart Failure

Results of the COPERNICUS Trial Published in the New England Journal of Medicine

New York, May 31, 2001 — The results of a large-scale multinational trial published in this week’s New England Journal of Medicine showed that the addition of carvedilol (a beta blocker with alpha-blocking properties) to conventional treatment dramatically reduced the risk of death in patients with advanced heart failure. Patients treated with carvedilol had a 35 percent (p=0.00013) lower risk of dying than patients treated with placebo. The COPERNICUS (CarvedilOl ProspEctive RaNdomiIzed CUmulative Survival) trial, conducted by thousands of researchers, including those at the Columbia University College of Physicians & Surgeons, also showed that carvedilol reduced the combined risk of death and hospitalization by 24 percent (p=0.0004) in patients with advanced stages of the disease who were already taking standard therapy, including ACE inhibitors.
“These results add considerably to the existing mandate that patients with heart failure should receive a beta blocker to improve symptoms and to prolong life,” said Dr. Milton Packer, Dickinson W. Richards, Jr., Professor of Medicine at Columbia University College of Physicians & Surgeons, Director of Heart Failure Center at Columbia Presbyterian Medical Center of New York-Presbyterian Hospital and the Principal Investigator of the trial. “Taken together with other evidence, the COPERNICUS trial shows that carvedilol is effective and well tolerated across the entire spectrum of patients with heart failure. We expect that this study will motivate physicians to take action to address the tremendous underutilization of this drug in appropriate patients with impaired cardiac function.”
COPERNICUS is the largest trial ever conducted in patients with advanced chronic heart failure with any drug. The study enrolled 2289 patients at 334 centers, who were treated with either placebo or carvedilol (in addition to conventional therapy) for up to 29 months. Conventional therapy consisted of diuretics and ACE inhibitors, and usually, digitalis. All patients had symptoms at rest or on minimal exertion and had a left ventricular ejection fraction less than 25 percent, but patients in an intensive care unit or receiving intravenous medications to stimulate the heart were not enrolled. The trial was stopped in March, 2000 upon the recommendation of the trial’s Data and Safety Monitoring Board (ethical committee), which observed a major mortality benefit with carvedilol and believed that it was unethical to continue treating patients with placebo. The Board proposed that all patients in the study be offered open-label treatment with carvedilol.
Earlier studies of beta blockers in heart failure primarily enrolled patients with mild or moderate symptoms and recruited few patients with symptoms at rest or on minimal exertion. The few trials that focused on advanced disease raised concerns that beta blockers may not be effective or may be deleterious in patients with Class IV heart failure. The lack of such data has likely contributed to the low utilization of beta blockers in the treatment of heart failure despite persuasive evidence that these drugs can prolong life in patients with mild or moderate disease.
A benefit was apparent in all subgroups of patients that were examined, including women and elderly patients, as well as patients who had extremely depressed cardiac function or who had been hospitalized multiple times for heart failure within one year of their entry into the study. In addition, the number of patients who needed to stop their study medication permanently because of adverse effects or other reasons was lower in the carvedilol group than in the placebo group.

Heart Failure is a Growing Epidemic
Heart failure develops when the heart is weakened and unable to pump blood efficiently through the body. It commonly results from damage to the heart after a heart attack, high blood pressure, or diabetes. Heart failure is the only major cardiovascular disease on the increase. Currently, it affects nearly five-million Americans. An estimated 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, averaging 250,000 annually.
The impact of heart failure has grown despite the use of digitalis, diuretics and ACE inhibitors. Despite compelling evidence about their benefits from previous studies, beta-blocking agents are dramatically under-utilized in the treatment of heart failure. It is estimated that less than 20 percent of patients with heart failure in the U.S. are receiving beta blockers. In Europe, fewer than five percent of patients with heart failure are receiving beta blockers.

New York-Presbyterian Hospital
New York-Presbyterian Hospital is a 2, 639-bed academic medical center created from the merger between The New York Hospital and The Presbyterian Hospital. It provides state-of-the-art inpatient, ambulatory, and preventative care in all areas of medicine at five major centers: New York Weill Cornell Medical Center, Columbia Presbyterian Medical Center, Children’s Hospital of New York, The Allen Pavilion, and the Westchester Division. One of the largest and most comprehensive health-care institutions in the world, the Hospital is committed to excellence in patient care, research, education, and community service. The New York-Presbyterian Healthcare system—which includes acute-care and community hospitals, long-term care facilities, home-health agencies, ambulatory sites, and specialty institutions—ensure high-quality, cost-effective, and conveniently accessible care to communities throughout the tri-state metropolitan region. The system serves over 20 percent of the patients in the New York Metropolitan area. The Hospital has academic affiliations with two of the country’s leading medical colleges: Joan and Sanford I. Weill Medical College of Cornell University and Columbia University College of Physicians & Surgeons.

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