The Effect of Carvedilol on Morbidity and Mortality in Patients with Chronic Heart Failure

Packer, Milton; Bristow, Michael R.; Cohn, Jay N.; Colucci, Wilson S.; Fowler, Michael B.; Gilbert, Edward M.; Shusterman, Neil H.

doi:10.1056/nejm199605233342101

Cited by 4,130 publications

(2,123 citation statements)

References 33 publications

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“…Therefore, data on the long‐term effect of newer generations of β‐blockers, such as bisoprolol, nebivolol, and carvedilol, are limited, which may have different properties and distinct effects from those of the first‐generation β‐blockers (ie, propranolol or timolol). In patients with heart failure and reduced ejection fraction, only long‐acting metoprolol, bisoprolol, and carvedilol have proven survival benefits, which indicates that the protective effect of β‐blockers is not a “class effect,” as seen in angiotensin‐converting enzyme inhibitors 7, 27, 28. In this study, 70% and 27% received third‐generation carvedilol and second‐generation bisoprolol, respectively, and our study results did not demonstrate different efficacies in patients with AMI, as reported in previous studies 13, 29…”

Section: Discussionmentioning

confidence: 99%

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Effect of β‐Blockers Beyond 3 Years After Acute Myocardial Infarction

Park

Kim

Kang

et al. 2018

JAHA

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BackgroundThe optimal duration of β‐blocker therapy in patients with acute myocardial infarction (AMI) is unknown. We aimed to evaluate the late effect of β‐blockers in patients with AMI.Methods and ResultsWe enrolled all consecutive patients who presented with AMI at Seoul National University Bundang Hospital, between June 3, 2003 and February 24, 2015. The primary end point was 5‐year all‐cause mortality, depending on the use of β‐blockers at discharge, 1 year after AMI, and 3 years after AMI. Of 2592 patients, the prescription rates of β‐blockers were 72%, 69%, 63%, and 60% at discharge and 1, 3, and 5 years after AMI, respectively. The patients who were receiving β‐blocker therapy had more favorable clinical characteristics, such as younger age (62 versus 65 years; P<0.001). They received reperfusion therapy more often (92% versus 80%; P<0.001) than those without β‐blocker prescription. In the univariate analysis, the patients with β‐blocker prescription had lower 5‐year mortality at all time points. In the Cox model after adjustment for significant covariates, β‐blocker prescription at discharge was associated with a 29% reduced mortality risk (hazard ratio, 0.71; 95% confidence interval, 0.55–0.90; P=0.006); however, β‐blocker prescriptions at 1 and 3 years after AMI were not associated with reduced mortality.ConclusionsThe beneficial effect of β‐blocker therapy after AMI may be limited until 1 year after AMI. Whether late β‐blocker therapy beyond 1 year after AMI offers clinical benefits should be confirmed in further clinical trials.

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Section: Discussionmentioning

confidence: 99%

“…Besides, they also have antiarrhythmic and antiremodeling effects 3. The effects of β‐blockers have been extensively investigated in patients with AMI,4, 5, 6, 7 and the current practice guidelines also recommend the use of β‐blockers in all patients after AMI unless contraindicated 1, 8…”

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confidence: 99%

Effect of β‐Blockers Beyond 3 Years After Acute Myocardial Infarction

Park

Kim

Kang

et al. 2018

JAHA

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“…Although recent large clinical trials have documented decreases in mortality and clinical deterioration in response to several different β ‐blockers, few evidence addressed the long‐term efficacy of metoprolol at maximally tolerated doses in HF secondary to IDCM, as well as its comparative data with ACEI/ARB therapy 13, 14, 15. Data from the present study indicated that metoprolol at optimized doses exhibited no significant difference from conventional low‐dose benazepril/valsartan in primary endpoint over 4‐year follow‐up, although it appeared to be more potent in reversing adverse remodelling.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and safety of supramaximal titrated inhibition of renin‐angiotensin‐aldosterone system in idiopathic dilated cardiomyopathy

Sun

Gao

et al. 2015

ESC Heart Failure

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AimsThe optimal dosing strategies for blocking the renin‐angiotensin‐aldosterone system in idiopathic dilated cardiomyopathy (IDCM) are poorly known. We sought to determine the long‐term efficacy and safety of supramaximal titration of benazepril and valsartan in patients with IDCM.Methods and results480 patients with IDCM in New York Heart Association functional class II–IV and with left ventricular ejection fraction ≤35% were randomly assigned to extended‐release metoprolol (mean 152 mg/day, range 23.75–190), low‐dose benazepril (20 mg/day), low‐dose valsartan (160 mg/day), high‐dose benazepril (mean 69 mg/day, range 40–80), and high‐dose valsartan (mean 526 mg/day, range 320–640). After a median follow‐up of 4.2 years, high‐dose benazepril and valsartan, compared with their respective low dosages, resulted in 41% and 52% risk reduction in the primary endpoint of all‐cause death or admission for heart failure (P = 0.042 and 0.002), promoted functional improvement, and reversed remodelling as assessed by New York Heart Association classes, quality‐of‐life scores, and echocardiographic recording of left ventricular ejection fraction, left ventricular end‐diastolic volume, mitral regurgitation, and wall motion score index. Compared with metoprolol, high‐dose valsartan reduced risk for the primary endpoint by 46% (P = 0.006), whereas high‐dose benazepril and both low‐dose groups showed no significant difference. Major adverse events involved hypotension and renal impairment but were largely tolerated.ConclusionsSupramaximal doses of benazepril and valsartan were well tolerated and produced extra benefit than their low dosages in clinical outcome and cardiac reverse remodelling in patients with IDCM and modest‐severe heart failure. ClinicalTrials.gov identifier: NCT01917149.

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“…Because HF hospitalization can be defined in various ways, and in order to ensure sufficient data for a meaningful analysis, data for surrogate measures of HF hospitalization were used in a number of studies 4, 5, 6, 7, 8, 9. The surrogate measures consisted of ‘ worsening heart failure requiring intravenous diuretic therapy or discontinuation of the study ’, ‘ intravenous furosemide for the control of acute exacerbations or symptoms ’, ‘ heart failure episode/decompensation ’, ‘ hospitalization for cardiovascular causes/reasons ’, ‘ cardiovascular hospitalization ’, and ‘ severe/resistant heart failure ’.…”

Section: Methodsmentioning

confidence: 99%

Varying effects of recommended treatments for heart failure with reduced ejection fraction: meta‐analysis of randomized controlled trials in the ESC and ACCF/AHA guidelines

2016

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The aim of this paper is to evaluate the treatment effects of recommended drugs and devices on key clinical outcomes for patients with heart failure with reduced ejection fraction (HFREF). Randomized controlled trials (RCTs) listed in the 2012 HF guideline from the European Society of Cardiology as well as the 2013 HF guideline from the American College of Cardiology Foundation and American Heart Association were evaluated for use in the meta‐analysis. RCTs written in English evaluating recommended drugs and devices for the treatment of patients with HFREF were included. Meta‐analyses, based on the outcomes of all‐cause mortality and hospitalization because of HF, were performed with relative risk ratio as the effect size. In the identified 47 RCTs, patients were on average 63 years old and 22% were female. Drugs targeting the renin‐angiotensin‐aldosterone system, beta‐blockers, cardiac resynchronization therapy (CRT), and intracardiac defibrillator devices (ICDs) significantly reduced the risk of death with reductions of 14–19, 23, 20, and 20%, respectively. Drugs targeting the renin‐angiotensin‐aldosterone system, beta‐blockers, digoxin, and CRT significantly reduced the risk of HF hospitalization with reductions of 24–37, 22, 60, and 36%, respectively, while ICDs significantly increased the risk with 34%. Ivabradine showed no significant effects on either outcome. As such, the majority of recommended HFREF treatments offered significant treatment benefits. However, many of the included studies were from the 1990s or earlier, and one must therefore be cautious when extrapolating these results to contemporary patients with HF.

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The Effect of Carvedilol on Morbidity and Mortality in Patients with Chronic Heart Failure

Abstract: Carvedilol reduces the risk or death as well as the risk of hospitalization for cardiovascular causes in patients with heart failure who are receiving treatment with digoxin, diuretics, and an angiotensin-converting-enzyme inhibitor.

Cited by 4,130 publications

References 33 publications

Effect of β‐Blockers Beyond 3 Years After Acute Myocardial Infarction

Effect of β‐Blockers Beyond 3 Years After Acute Myocardial Infarction

Efficacy and safety of supramaximal titrated inhibition of renin‐angiotensin‐aldosterone system in idiopathic dilated cardiomyopathy

Varying effects of recommended treatments for heart failure with reduced ejection fraction: meta‐analysis of randomized controlled trials in the ESC and ACCF/AHA guidelines

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