COPERNICUS: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Determine the Effect of Carvedilol on Mortality in Patients with Severe Chronic Heart Failure Milton Packer Columbia University College of Physicians and Surgeons, New York, USA Previous clinical trials have clearly demonstrated the favorable effect of carvedilol therapy on mortality among patients with mild-to-moderate heart failure. The COPERNICUS Trial has now demonstrated a significant reduction in mortality among patients with severe heart failure who receive carvedilol therapy. Preliminary results had been previously announced for the COPERNICUS trial, which added carvedilol to standard therapy for patients with severe heart failure. The study showed a 35% reduction in all-cause mortality (P << .001) at 21 months, leading the supervising authorities to suspend the trial at that point. At this meeting, Dr. Packer said: "Here today, for the first time, we are announcing all of the other major results of this landmark clinical trial." COPERNICUS included 2,289 patients with symptoms of heart failure at rest or with minimal exertion and with a left ventricular ejection fraction below 25% despite diuretics and angiotensin-converting enzyme (ACE) inhibitors, as well as with use of digoxin if indicated. The results showed that carvedilol significantly reduced all of the following clinical endpoints: Death or hospitalization: 24% Death or cardiovascular hospitalization: 27% Death or hospitalization for heart failure: 31% Any hospitalization: 20% Cardiovascular hospitalization: 28% Heart failure hospitalization: 33% Total days in hospital: 27% Number of hospital admissions: 20% Number of days per admission: 9% All of these reductions were statistically significant. In addition, the number of treatments used (such as IV diuretics, IV inotropic drugs) or the use of echocardiography during hospitalization was reduced. Both the duration and intensity of hospitalizations were reduced for patients receiving carvedilol, and patientsﾕ global assessments improved, as well. Fewer adverse events occurred in the carvedilol group, including worsening heart failure, arrhythmia, and sudden death (p < .05). Perhaps most importantly, there was no increase in the incidence of adverse events during initiation and titration of carvedilol therapy (the possibility of negative effects has often been a concern among physicians beginning beta-blocker therapy in heart failure patients). Dr. Packer pointed out that the benefits of carvedilol may be related to the severity of the disease and that the sickest patients may benefit the most. In response to a question about the historical context of use of beta-blockers in heart failure, Dr. Packer said: "our philosophy of heart failure has changed in the last 10 or 15 years. We used to think of heart failure as a purely hemodynamic phenomenon in terms of a simple decrease in myocardial contractility. In that context, you would not want to give a heart failure patient a negative inotrope. However, we now understand heart failure essentially to be a manifestation of chronic abnormal neurohormonal activation, so blockade of adrenergic stimuli to the heart is beneficial." Reporter: Andre Weinberger, MD Copyright 2000-2013 by HESCO International, Ltd. All rights reserved.