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| TITLE |
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Effect of carvedilol on the morbidity of patients with severe chronic heart failure: results of the carvedilol prospective randomized cumulative survival (COPERNICUS) study.
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| AUTHORS |
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Milton Packer, Michael B. Fowler, Ellen B. Roecker, Andrew J. S. Coats, Hugo A. Katus, Henry Krum, Paul Mohacsi, Jean L. Rouleau, Michal Tendera, Christoph Staiger, Terry L Holcslaw, Ildiko Amann-Zalan, David L. DeMets, the COPERNICUS Study Group
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| PUBLICATION INFORMATION |
Journal Name: Circulation
Volume: 106(17)
Pages: 2194-9
Date Published: 10/22/2002
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| ABSTRACT/REVIEW |
What were the researchers trying to learn in this study?
They wanted to know if the beta-blocking drug carvedilol improves patients' ability to function and reduces illness (morbidity) in severe heart failure.
In this analysis, the researchers describe the effects of carvedilol on morbidity in the COPERNICUS study, both subjectively by asking patients to judge how they felt and objectively by recording major clinical events such as the number and length of hospital stays. Specifically, the researchers asked the patients at set times during follow-up whether his or her health had markedly, moderately, or slightly improved, had remained unchanged, or had slightly, moderately, or markedly worsened since the start of the study.
Carvedilol (KAR-ve-dil-ole), sold under the brand name Coreg® by GlaxoSmithKline, belongs to a group of medicines called beta-adrenergic blocking agents, or more commonly, beta-blockers. Beta-blockers work by affecting the response to some nerve impulses in certain parts of the body. As a result, they decrease the heart's need for blood and oxygen by reducing its workload. Beta-blockers are used in the treatment of high blood pressure (hypertension). Some beta-blockers are also used to relieve angina (chest pain) and in heart attack patients to help prevent additional heart attacks.
What did they find?
Although the purpose of this analysis focuses on morbidity, a prior report on these 2,289 patients showed that there were 314 patients who died or who were hospitalized for a cardiovascular reason in the carvedilol group compared to 395 such patients in the placebo (inactive sugar pill) group. This represents a 30.2% chance of dying within 1 year from study entry for those treated with carvedilol compared to 41.6% chance of dying for those taking the placebo.
Carvedilol reduced the combined risk of death or hospitalization for a cardiovascular reason by 27% and the combined risk of death or hospitalization for heart failure by 31% as compared to those treated with placebo.
Patients in the carvedilol group also spent 27% fewer days in the hospital for any reason and 40% fewer days in the hospital for heart failure than those taking the placebo. These differences were a result of both a decrease in the number of hospitalizations and a shorter duration of each admission.
More patients felt improved and fewer patients felt worse in the carvedilol group than in the placebo group after 6 months of maintenance therapy. Carvedilol-treated patients were also less likely than placebo-treated patients to experience a serious adverse event, especially worsening heart failure, sudden death, cardiogenic shock, or ventricular tachycardia. Cardiogenic shock is a disease state in which the heart is damaged enough that it is unable to supply sufficient blood to the body, and ventricular tachycardia is rapid heart beat usually above 100 beats per minute.
Who was studied?
Patients were enrolled if they had difficulty breathing (dyspnea) or fatigue at rest or on minimal exertion for more than 2 months and poor heart function due to low blood flow to the heart muscle (left ventricular ejection fraction less than 25% as a result of an ischemic or nonischemic cardiomyopathy).
All patients received blood pressure lowering therapy in the form of a diuretic to increase urine discharge and reduce fluid retention, which was adjusted to minimize the degree of fluid retention, together with either an angiotensin converting enzyme (ACE) inhibitor or an angiotensin II receptor antagonist (unless these were not tolerated).
Treatment with other medications typically given for heart failure (digitalis, spironolactone, vasodilators, and amiodarone) was allowed, but not required. Patients could be inpatients or outpatients, but they could not have an acute illness that required continued hospitalization.
How was the study done?
They randomly assigned 2,289 patients with symptoms of heart failure at rest or on minimal exertion and with an ejection fraction of less than 25% to treatment with either carvedilol (1,156) or placebo (1,133) in addition to their usual
medications for heart failure for an average of 10.4 months. Each patient then entered a maintenance phase, during which he or she was seen as an outpatient every 2 months until the end of the study.
The primary aim of the study was to measure patient hospitalizations or death following the start of the trial. This report, however, focuses on 4 prespecified secondary study objectives. These included the combined risk of death or hospitalization for any reason, the combined risk of death or hospitalization for a cardiovascular reason, the combined risk of death or hospitalization for heart failure, and the patient global assessment, or the subjective responses of patients to questions about how they felt overall following study enrollment.
What did researchers know before starting this study?
Earlier studies of patients with mild-to-moderate heart failure have shown significantly fewer serious adverse events due to the ill effects of their heart failure. Beta-Blocking agents improved patients' ability to perform normal activities and reduced illness (morbidity) in these mild-to-moderate heart failure patients.
Why did they do it?
They wanted to know if beta-blockers would provide advanced heart failure patients with similar benefits of extended survival and improved quality of life from carvedilol therapy as had been experienced by mild-to-moderate heart failure patients.
What did the researchers say their study results mean?
The researchers concluded that for advanced heart failure patients with symptoms at rest or with minimal exertion, the addition of carvedilol to conventional therapy reduces the severity of heart failure symptoms and reduces the risk of worsening condition, hospitalization, and other serious adverse clinical events.
Author disclosures:
Drs. Packer, Fowler, Coats, Katus, Krum, Mohacsi, Rouleau, Tendera, and DeMets have served as consultants. Dr. Roecker's salary is supported by a research grant. Dr. Amann-Zalan is a current employee and Dr Staiger is a former employee of Roche Pharmaceuticals. Dr. Holcslaw is an employee of GlaxoSmithKline Ltd.
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