Effect of Carvedilol on Survival in Severe Chronic Heart Failure

Packer, Milton; Coats, Andrew J.S.; Fowler, Michael B.; Katus, Hugo A.; Krum, Henry; Mohaçsi, Paul; Rouleau, Jean‐Lucien; Tendera, Michał; Castaigne, A; Roecker, Ellen B.; Schultz, M.; DeMets, David L.

doi:10.1056/nejm200105313442201

Cited by 2,797 publications

(921 citation statements)

References 29 publications

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“…In mid‐1990s, the American Heart Association and the American College of Cardiology published the first clinical guidelines for heart failure (HF) 2, 3. Based in large part on the results of the SOLVD (Studies of Left Ventricular Dysfunction),4 SAVE (Survival and Ventricular Enlargement),5 CONSENSUS (Cooperative North Scandinavian Enalapril Survival Study),6 COPERNICUS (Carvedilol Prospective Randomized Cumulative Survival Study),7 MERIT‐HR (Metoprolol CR/XL Randomized Intervention Trial in Congestive Heart Failure),8 and CIBIS‐II (Cardiac Insufficiency Bisoprolol Study II)9 trials, HF guidelines have consistently focused on the benefits of neurohormonal therapy to delay progression and improve survival for patients with HF with reduced ejection fraction (HFrEF). More recent guidelines have also included emphasis on the importance of achieving and maintaining decongestion regardless of ejection fraction 10, 11, 12…”

Section: Introductionmentioning

confidence: 99%

Reasons for Guideline Nonadherence at Heart Failure Discharge

Gilstrap

Stevenson

Small

et al. 2018

JAHA

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BackgroundCardiology has advanced guideline development and quality measurement. Recognizing the substantial benefits of guideline‐directed medical therapy, this study aims to measure and explain apparent deviations in heart failure (HF) guideline adherence by clinicians at hospital discharge and describe any impact on readmission rates.Methods and ResultsThe extent of decongestion and prescription of neurohormonal therapy were recorded prospectively for 226 HF discharges, including 132 (58%) from an academic hospital and 94 (42%) from a community hospital. Among all discharges, 25% were discharged with residual congestion (30% academic versus 18% community, P=0.070). Among discharges of patients with HF with reduced ejection fraction, 37% (45% academic versus 18% community, P<0.001) were discharged without β‐blocker therapy or with lower doses than at admission. Moreover, 46% of patients with HF with reduced ejection fraction (48% academic versus 39% community, P=0.390) were discharged without an angiotensin‐converting enzyme inhibitor or angiotensin II receptor blocker or with lower doses than at admission. Renal dysfunction was the most common reason for discharge with congestion, and hypotension the most common reason for discharge with no or decreased neurohormonal therapy. There was a trend toward higher 90‐day readmission rates after discharge with residual congestion.ConclusionsClinicians frequently deviate from guidelines in both academic and community hospitals; however, this deviation may not always indicate poor quality. Application of guidelines recommended for stable populations is increasingly limited for hospitalized patients by hypotension, renal dysfunction, and inotrope use. Patients with renal dysfunction, hypotension, and recent inotrope use merit further study to determine best practices and possibly to adjust quality metrics for HF severity.

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Section: Introductionmentioning

confidence: 99%

Reasons for Guideline Nonadherence at Heart Failure Discharge

Gilstrap

Stevenson

Small

et al. 2018

JAHA

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“…We prospectively evaluated the patients enrolled in the Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS) trial, the design and primary results of which have been previously published 9. A total of 2289 patients with dyspnoea at rest or on minimal exertion and a left ventricular ejection fraction <25% despite appropriate therapy were randomly assigned (in a double‐blind fashion) to receive either placebo ( n = 1133) or carvedilol ( n = 1156) and were followed for the occurrence of major clinical events for up to 29 months.…”

Section: Methodsmentioning

confidence: 99%

“…Considering the survival benefit of carvedilol, however,9 these analyses are biased in favour of placebo and therefore underestimate any effect of carvedilol.…”

Section: Methodsmentioning

confidence: 99%

Effect of beta‐adrenergic blockade with carvedilol on cachexia in severe chronic heart failure: results from the COPERNICUS trial

Clark

Coats

Krum

et al. 2017

J cachexia sarcopenia muscle

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BackgroundCardiac cachexia frequently accompanies the progression of heart failure despite the use of effective therapies for left ventricular dysfunction. Activation of the sympathetic nervous system has been implicated in the pathogenesis of weight loss, but the effects of sympathetic antagonism on cachexia are not well defined.MethodsWe prospectively evaluated changes in body weight in 2289 patients with heart failure who had dyspnoea at rest or on minimal exertion and a left ventricular ejection fraction <25%. Patients were randomly assigned (double‐blind) to receive either placebo (n = 1133) or carvedilol (n = 1156) and were followed for the occurrence of major clinical events for up to 29 months (COPERNICUS trial). Patients were not enrolled if they had signs of clinically significant fluid retention due to heart failure.ResultsPatients in the carvedilol group were 33% less likely than patients in the placebo group to experience a further significant loss of weight (>6%) (95% confidence interval: 14–48%, P = 0.002) and were 37% more likely to experience a significant gain in weight (≥5%) (95% confidence interval: 12–66%, P = 0.002). Carvedilol's ability to prevent weight loss was most marked in patients with increased body mass index at baseline, whereas its ability to promote weight gain was most marked in patients with decreased body mass index at baseline. Increases in weight were not accompanied by evidence of fluid retention. Baseline values for body mass index and change in body weight were significant predictors of survival regardless of treatment.ConclusionsCarvedilol attenuated the development and promoted a partial reversal of cachexia in patients with severe chronic heart failure, supporting a role for prolonged sympathetic activation in the genesis of weight loss.

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“…Advanced HF was defined according to the criteria applied by COPERNICUS study2 as one or more of the following: the presence of pulmonary rales, ascites, or peripheral edema; frequent (≥3) hospitalizations for ADHF within the previous year; the need for an intravenous positive inotrope or an intravenous vasodilator within 2 weeks before enrollment; or a left ventricular ejection fraction (LVEF) of equal or less than 15%.…”

Section: Methodsmentioning

confidence: 99%

“…The majority of hospitalized patients with ADHF will be readmitted with recurrent symptoms or will die within a few months. As defined by the Carvedilol prospective randomized cumulative survival (COPERNICUS) study, frequent (three or more) hospitalizations for acute decompensation within a year is one of the major characteristics of advanced HF 2. As a result, a growing body of interest is seen in recent literature investigating the application of various physical examination findings, laboratory measurements, and ultrasonographic and echocardiographic indices in the prediction of both short‐term and long‐term rehospitalization and death in ADHF patients.…”

Section: Introductionmentioning

confidence: 99%

On admission serum sodium and uric acid levels predict 30 day rehospitalization or death in patients with acute decompensated heart failure

et al. 2017

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AimsA considerable proportion of hospitalized patients for acute decompensated heart failure will be readmitted or die in short‐term follow‐up. In the present study, we aimed to assess the role of admission sodium (Na) and uric acid (UA) levels in the prediction of 30 day post‐discharge heart failure readmission or all‐cause mortality in advanced heart failure patients admitted with acute decompensation.Methods and resultsOne hundred and forty consecutive advanced heart failure patients who were admitted for a recent cardiac decompensation were enrolled in this prospective study. Serum Na and UA levels remained statistically unchanged during index admission (P = 0. 54 and 0.19, respectively). Within 30 days post‐discharge, composite end point of heart failure rehospitalization or all‐cause death occurred in 62 (44.3%) patients (event group). Length of stay was statistically similar between patients in the event and non‐event groups (P = 0.38). No correlations were also found between length of stay and left ventricular ejection fraction, serum Na, UA, erythrocyte sedimentation rate (ESR), high‐sensitivity C‐reactive protein (hs‐CRP), creatinine, and N‐terminal pro b‐type natriuretic peptide (NT‐proBNP) levels (all P > 0.05). Lower left ventricular ejection fraction and Na and higher UA on admission were significantly associated with 30 day event both in univariate and multivariate analyses.ConclusionsGiven the predictive role of baseline Na and UA for early post‐discharge outcome and the absence of significant changes in their levels during initial hospitalization, admission Na and UA can be considered as prognosticators of acute decompensated heart failure, which their prognostic significance cannot be affected by routine acute heart failure therapy.

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Effect of Carvedilol on Survival in Severe Chronic Heart Failure

Abstract: The previously reported benefits of carvedilol with regard to morbidity and mortality in patients with mild-to-moderate heart failure were also apparent in the patients with severe heart failure who were evaluated in this trial.

Cited by 2,797 publications

References 29 publications

Reasons for Guideline Nonadherence at Heart Failure Discharge

Reasons for Guideline Nonadherence at Heart Failure Discharge

Effect of beta‐adrenergic blockade with carvedilol on cachexia in severe chronic heart failure: results from the COPERNICUS trial

On admission serum sodium and uric acid levels predict 30 day rehospitalization or death in patients with acute decompensated heart failure

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