***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
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    Input: OBJECTIVES We performed a post-hoc subgroup analysis in the Metoprolol CR/XL R and omized Intervention Trial in Chronic Heart Failure ( MERIT-HF ) with the aim of reporting on the heart rate ( HR ) response during the titration phase and clinical outcomes from the three-month follow-up visit to end of study in two dosage subgroups : one that had reached more than 100 mg of metoprolol CR/XL once daily ( high-dose group ; n = 1,202 ; mean 192 mg ) and one that had reached 100 mg or less ( low-dose group ; n = 412 ; mean 76 mg ) . BACKGROUND Clinicians have question ed whether patients need to reach the target beta-blocker dose to receive benefit . METHODS ; Outcome ( Cox-adjusted ) was compared with all  placebo  patients with dose available at the three-month visit ( n = 1,845 ) . RESULTS Data indicated somewhat higher risk in the low-dose group compared with the high-dose group . Heart rate was reduced to a similar degree in the two dose groups , indicating higher sensitivity for beta-blockade in the low-dose group . The reduction in total mortality with metoprolol CR/XL compared with placebo was similar : 38 % ( 95 % confidence interval [ CI ] , 16 to 55 ) in high-dose group ( p = 0.0022 ) and also 38 % ( 95 % CI , 11 to 57 ) in the low-dose group ( p = 0.010 ) . CONCLUSIONS Risk reduction was similar in the high- and low-dose subgroups , which , at least partly , may be the result of similar beta-blockade as judged from the HR response . The results support the idea of an individualized dose-titration regimen , which is guided by patient tolerability and the HR response . Further research is needed to shed light on why some patients respond with a marked HR reduction and reduced mortality risk on a relatively small dose of a beta-blocker BACKGROUND Both metoprolol and carvedilol produce hemodynamic and clinical benefits in patients with chronic heart failure ;  carvedilol exerts greater antiadrenergic effects than metoprolol , but it is unknown whether this pharmacological difference results in hemodynamic and clinical differences between the 2 drugs . METHODS AND RESULTS We r and omized 150 patients with heart failure ( left ventricular ejection fraction < /=0.35 ) to double-blind treatment with either metoprolol or carvedilol . When compared with metoprolol ( 124+/-55 mg/d ) , patients treated with carvedilol ( 49+/-18 mg/d ) showed larger increases in left ventricular ejection fraction at rest ( + 10.9+/-11.0 versus + 7.2+/-7.7 U , P=0.038 ) and in left ventricular stroke volume and stroke work during exercise ( both P<0 . 05 ) after 13 to 15 months of treatment . In addition , carvedilol produced greater decreases in mean pulmonary artery pressure and pulmonary wedge pressure , both at rest and during exercise , than metoprolol ( all P<0.05 ) . In contrast , the metoprolol group showed greater increases in maximal exercise capacity than the carvedilol group ( P=0.035 ) , but the 2 drugs improved symptoms , submaximal exercise tolerance , and quality of life to a similar degree . After a mean of 23+/-11 months of follow-up , 21 patients in the metoprolol group and 17 patients in the carvedilol group died or underwent urgent transplantation . CONCLUSIONS The present study demonstrates that during long-term therapy , carvedilol improves cardiac performance to a greater extent than metoprolol when administered to patients with heart failure in the doses shown to be effective in clinical trials . These differences were likely related to a greater antiadrenergic activity of carvedilol BACKGROUND The beneficial effects of beta-blockers on long-term outcome after acute myocardial infa rct ion were shown before the introduction of thrombolysis and angiotensin-converting-enzyme ( ACE ) inhibitors . Generally , the patients recruited to these trials were at low risk : few had heart failure , and none had measurements of left-ventricular function taken . We investigated the long-term efficacy of carvedilol on morbidity and mortality in patients with left-ventricular dysfunction after acute myocardial infa rct ion treated according to current evidence -based practice . METHODS In a multicentre , r and omised , placebo-controlled trial , 1959 patients with a proven acute myocardial infa rct ion and a left-ventricular ejection fraction of < /=40 % were r and omly assigned 6.25 mg carvedilol ( n=975 ) or placebo ( n=984 ) . Study medication was progressively increased to a maximum of 25 mg twice daily during the next 4 - 6 weeks , and patients were followed up until the requisite number of primary endpoints had occurred . The primary endpoint was all-cause mortality or hospital admission for cardiovascular problems . Analysis was by intention to treat . FINDINGS Although there was no difference between the carvedilol and placebo groups in the number of patients with the primary endpoint ( 340 [ 35 % ] vs 367 [ 37 % ] , hazard ratio 0.92 [ 95 % CI 0.80 - 1.07 ] ) , all-cause mortality alone was lower in the carvedilol group than in the placebo group ( 116 [ 12 % ] vs 151 [ 15 % ] , 0.77 [ 0.60 - 0.98 ] , p=0.03 ) . Cardiovascular mortality , non-fatal myocardial infa rct ions , and all-cause mortality or non-fatal myocardial infa rct ion were also lower on carvedilol than on placebo . INTERPRETATION In patients treated long-term after an acute myocardial infa rct ion complicated by left-ventricular systolic dysfunction , carvedilol reduced the frequency of all-cause and cardiovascular mortality , and recurrent , non-fatal myocardial infa rct ions . These beneficial effects are additional to those of evidence -based treatments for acute myocardial infa rct ion including ACE inhibitors BACKGROUND We investigated the effects of bucindolol , a nonselective , non-ISA beta-blocker with mild-vasodilatory properties , in patients with congestive heart failure from ischemic dilated cardiomyopathy ( ISCDC , n = 27 ) and compared the results with those in subjects with heart failure from idiopathic dilated cardiomyopathy ( IDC , n = 22 ) . METHODS AND RESULTS Patients were r and omized in a double-blind fashion to receive 12 weeks ' treatment with either bucindolol or placebo , with r and omization stratified for IDC or ISCDC : Invasive ( right heart catheterization ) and noninvasive ( echo , MUGA , central venous norepinephrine , exercise treadmill studies , and symptom scores ) tests of heart failure severity were determined at baseline and end of the study . For all subjects ( ISCDC plus IDC ) , relative to placebo treatment , bucindolol-treated patients had significant improvement in ejection fraction , left ventricular size and filling pressure , stroke work index , symptom score , and central venous norepinephrine . However , most of these differences could be attributed to improvement in the IDC subgroup , as the only parameter with a statistically significant degree of improvement in the bucindolol-treated ISCDC subgroup was left ventricular size . CONCLUSIONS We conclude that beta-blockade may produce quantitatively different degrees of response in different kinds of heart muscle disease BACKGROUND Small-scale clinical investigations have demonstrated that single doses of beta-blocking agents can improve left ventricular function in heart failure from idiopathic dilated cardiomyopathy ( IDC ) . The purpose of this multicenter clinical trial was to determine the dose-effect characteristics of beta-blockade in a heart failure population that includes ischemic dilated cardiomyopathy ( ISCD ) . METHODS AND RESULTS Bucindolol is a nonselective beta-blocking agent with mild vasodilatory properties . One hundred forty-one subjects with class II or III heart failure , left ventricular ejection fraction ( LVEF ) < or = 0.40 , and background therapy of angiotensin-converting enzyme inhibitors , digoxin , and diuretics were given an initial challenge dose of bucindolol 12.5 mg . One hundred thirty-nine subjects ( 99 with IDC , 40 with ISCDC ) tolerated challenge and were r and omized to treatment with placebo or bucindolol 12.5 mg/d ( low dose ) , 50 mg/d ( medium dose ) , or 200 mg/d ( high dose ) . At the end of 12 weeks , left ventricular function and other parameters were measured and compared with baseline values . There was a dose-related improvement in left ventricular function in bucindolol-treated subjects . In the high-dose bucindolol group , radionuclide-measured LVEF improved by 7.8 EF units ( % ) compared with 1.8 units in the placebo group ( P < .05 ) , and compared with the placebo group , a greater percentage of subjects had an increase in LVEF by > or = 5 units . In contrast , all three bucindolol doses prevented deterioration of myocardial function as defined by an LVEF decline of > or = 5 units . CONCLUSIONS In heart failure from systolic dysfunction , beta-blockade with bucindolol produces a dose-related improvement in and prevents deterioration of left ventricular function OBJECTIVES We sought to evaluate the effects of carvedilol on mortality and morbidity in dialysis patients with dilated cardiomyopathy . BACKGROUND Several lines of evidence support the concept that therapy with beta-blocking agents reduces morbidity and mortality in patients with congestive heart failure ( HF ) , but the demonstration of such a survival benefit in dialysis patients with dilated cardiomyopathy is still lacking . METHODS A total of 114 dialysis patients with dilated cardiomyopathy were r and omized to receive either carvedilol or placebo in addition to st and ard therapy . A first analysis was performed at one year and was followed by an additional follow-up period of 12 months . RESULTS Two-year echocardiographic data revealed a significant attenuation of pathologic remodeling , with smaller cavity diameters and higher ejection fractions in the active treatment group than in the placebo group . At two years , 51.7 % of the patients died in the carvedilol group , compared with 73.2 % in the placebo group ( p < 0.01 ) . Furthermore , there were significantly fewer cardiovascular deaths ( 29.3 % ) and hospital admissions ( 34.5 % ) among patients receiving carvedilol than among those receiving a placebo ( 67.9 % and 58.9 % , respectively ; p < 0.00001 ) . The exploratory analyses revealed that fatal myocardial infa rct ions , fatal strokes , and hospital admissions for worsening HF were lower in the carvedilol group than in the placebo group . A reduction in sudden deaths and pump-failure deaths was also observed , though it did not reach statistical significance . CONCLUSIONS Carvedilol reduced morbidity and mortality in dialysis patients with dilated cardiomyopathy . These data suggest the use of carvedilol in all dialysis patients with chronic HF OBJECTIVES This study was performed to compare the long-term clinical efficacy of treatment with metoprolol versus carvedilol in patients with chronic heart failure . BACKGROUND Beta-adrenergic blockade is of proven value in chronic heart failure .  Metoprolol , a selective beta-blocker , is widely used , but recent trials suggest carvedilol , a nonselective beta-blocker with alpha-1-receptor antagonist activity and antioxidant activities , is also effective . It is uncertain , however , if these additional properties of carvedilol provide further clinical benefit compared with metoprolol . METHODS In this r and omized double-blind control trial , 51 patients with chronic heart failure and mean left ventricular ( LV ) ejection fraction of 26 % + /- 1.8 % were r and omly assigned treatment with metoprolol 50 mg twice daily or carvedilol 25 mg twice daily in addition to st and ard therapy after a four-week dose titration period for a total of 12 weeks . Response was assessed by a quality of life question naire , New York Heart Association class , exercise capacity ( 6-min walk test ) , radionucleotide ventriculography for LV ejection fraction , two-dimensional echocardiography measurement of LV dimensions and diastolic filling and 24-h electrocardiograph monitoring to assess heart rate variability . RESULTS Both carvedilol and metoprolol produced highly significant improvement in symptoms ( p < 0.001 ) , exercise capacity ( p < 0.05 ) and LV ejection fraction ( p < 0.001 ) , and there were no significant differences between the two drugs . Carvedilol had a significantly greater effect on sitting and st and ing blood pressure , LV end-diastolic dimension and normalized the mitral E wave deceleration time . CONCLUSIONS Both metoprolol and carvedilol were equally effective in improving symptoms , quality of life , 
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In this sense , enrollment may have limited more severe grade s of these comorbidities .
Conclusions RCTs provide authoritative information for a spectrum of CHF presentations that support guidelines .