Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “FAILURE”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 289 records · Page 16Linked to original sources
PubMed2006

Prognostic value of a novel classification scheme for heart failure: the Minnesota Heart Failure Criteria.

The authors present the Minnesota Heart Failure Criteria (MHFC), derived using latent class analysis from widely available items in the Framingham Criteria. The authors used 1995 and 2000 data on hospitalized Minnesota Heart Survey subjects discharged after myocardial infarction or heart failure (N = 7,379). Selected Framingham Criteria variables (dyspnea, pulmonary rales, cardiomegaly, interstitial or pulmonary edema on chest radiograph, S(3) heart sound, tachycardia) plus left ventricular ejection fraction were used. The discriminatory power of the MHFC was evaluated using age- and sex-adjusted 2-year mortality. A five-class latent class analysis model was collapsed into cases and noncases. Mortality estimates discriminated noncases (18%) from cases (43%) (p < 0.001). The MHFC performed better than previous truncated criteria (Framingham Criteria: 26% noncases, 43% cases; Duke Criteria: 29%, 40%; Killip Score: 31%, 44%; Boston Score: 28%, 45%). In a subset of patients admitted for heart failure (n = 5,128), the MHFC identified all but 2% (116/4,746) of cases found with a nearly full version of the Framingham Criteria. In terms of prognostic value, the MHFC are as precise as or more precise than several previous sets of truncated criteria. They closely approximate a nearly full version of the Framingham Criteria but require many fewer variables and can facilitate epidemiologic case-finding for heart failure.

Adult↗
PubMed1994

Dose-related effects of ACE inhibition in man: quinapril in patients with moderate congestive heart failure. The Study Group on Neurohormonal Regulation in Congestive Heart Failure: Lausanne, Switzerland; Berlin, Düsseldorf, Munich, Germany.

Early treatment with ACE inhibitors of even moderate heart failure is clinically beneficial, even though haemodynamic measurements cannot adequately quantitate such improvement. Neurohumoral assessment is, however, supposed to be more accurate. In 55 patients with moderate heart failure (ejection fraction < or = 35%), we investigated the dose-dependent effects of ACE inhibition with quinapril taken orally (2.5, 5 or 10 mg b.i.d.) following a placebo-controlled, parallel design protocol over 12 weeks. Plasma components of the renin angiotensin system, catecholamines and ANF were measured together with haemodynamics both at rest and during exercise. Before ACE inhibitor treatment, median PRA, Ang I and II and catecholamines were normal, while ANF was increased. All these parameters, including ACE activity, rose during exercise. Chronic inhibition of ACE activity was dose-dependent and the maximal fall in Ang II occurred with quinapril 20 mg.day-1. Humoral changes appeared more assessible than haemodynamic alterations even though many of these changes were reasonably correlated. The effects of chronic ACE inhibition on circulating neurohumoral components in patients with moderate heart failure are small and dose-dependent. Since humoral changes are related to haemodynamics they should account for the clinical benefit. Appropriately high doses of ACE inhibitors should be chosen for treatment of heart failure.

Administration, Oral↗
PubMed2005

Under-utilization of evidence-based drug treatment in patients with heart failure is only partially explained by dissimilarity to patients enrolled in landmark trials: a report from the Euro Heart Survey on Heart Failure.

AIMS: Surveys on heart failure management suggest under-utilization of life-saving evidence-based treatment. Evidence-based medicine and clinical guidelines are based on the results of randomized controlled trials. Therefore, we investigated how patients who fulfilled the enrolment criteria of randomized trials were treated in real life. METHODS AND RESULTS: We selected three large placebo-controlled trials of patients with chronic heart failure, in which ACE-inhibitors (ACE-Is), beta-blockers, and spironolactone proved to be safe and effective. The major enrolment criteria of trials were identified and applied to patients enrolled in the Euro Heart Survey on Heart Failure to identify the proportion of patients eligible for treatment and also treated appropriately. Of the 10 701 patients who were enrolled in the Euro Heart Survey on Heart Failure, only a small percentage (13%) would have qualified for participation in at least one of the selected trials. Patients who fulfilled enrolment criteria of the identified trials were more likely to be treated with ACE-Is (83% of SOLVD-eligible patients), beta-blockers (54% of MERIT-HF-eligible patients), and aldosterone antagonists (43% of RALES-eligible patients) than trial-ineligible patients. Almost half of SOLVD-eligible patients who were treated with ACE-Is received the target dose as recommended in the guidelines, but only <10% of MERIT-HF eligible patients who were treated with beta-blockers received the target dose. CONCLUSION: ACE-Is are widely utilized but given in lower doses than proven effective in clinical trials. beta-Blockers are underused and given in lower doses to patients who fulfil the enrolment criteria of relevant landmark trials.

Adrenergic beta-Antagonists↗
PubMed2006

Longer-term effects of cardiac resynchronization therapy on mortality in heart failure [the CArdiac REsynchronization-Heart Failure (CARE-HF) trial extension phase].

AIMS: The CArdiac REsynchronization-Heart Failure study randomized patients with left ventricular ejection fraction < or =35%, markers of cardiac dyssynchrony, and persistent moderate or severe symptoms of heart failure despite pharmacological therapy, to implantation of a cardiac resynchronization therapy (CRT) device or not. The main study observed substantial benefits on morbidity and mortality during a mean follow-up of 29.4 months [median 29.6, interquartile range (IQR) 23.6-34.6]. Prior to study closure, an extension phase lasting a further 8 months (allowing time for data analysis and presentation) was declared during which cross-over was discouraged. METHODS AND RESULTS: This was an extension of the already reported open-label randomized trial described above. The primary outcome of the extension phase was all-cause mortality from the time of randomization to completion of the extension phase. The secondary outcome was mode of death. The mean follow-up was 37.4 months (median 37.6, IQR 31.5-42.5, range 26.1-52.6 months). There were 154 deaths (38.1%) in 404 patients assigned to medical therapy and 101 deaths (24.7%) in 409 patients assigned to CRT (hazard ratio 0.60, 95% CI 0.47-0.77, P<0.0001) without evidence of heterogeneity in pre-specified subgroups. A reduction in the risk of death due to heart failure (64 vs. 38 deaths; hazard ratio 0.55, 95% CI 0.37-0.82, P=0.003) and sudden death was observed (55 vs. 32; hazard ratio 0.54, 95% CI 0.35-0.84, P=0.005). CONCLUSION: The benefits of CRT observed in the main trial persist or increase with longer follow-up. Reduction in mortality was due to fewer deaths both from worsening heart failure and from sudden death.

Aged↗
PubMed2006

Management of octogenarians hospitalized for heart failure in Euro Heart Failure Survey I.

AIMS: Here, the aim is to study the management of octogenarians hospitalized for heart failure in Euro Heart Failure Survey I. Heart Failure (HF) is common in older people and associated with poor outcome. METHODS AND RESULTS: We compared clinical characteristics, treatment, and short-term outcomes in 2780 octogenarians (group A, median age 85 years) and in 7912 younger patients (group B, median age 69 years) enrolled in the Euro Heart Failure Survey I. There were 37% males in group A vs. 59% in group B (P < 0.001). Co-morbidities were more common in group A. Ejection fraction was measured only in 38% in group A vs. 65% in group B (P < 0.001) and when measured was preserved in 50 vs. 40% (P < 0.001). In-hospital and 12 weeks follow-up mortality were, respectively, 13 vs. 5% (P < 0.001) and 12 vs. 6% (P < 0.001) in groups A and B. Acute cardiac conditions and co-morbidity predicted mortality, whereas the use of angiotensin-converting enzyme inhibitor (ACE-I) and beta-blockers was associated with a better outcome. ACE-I and beta-blockers were used in 50 vs. 66% (P < 0.001) and 24 vs. 42% (P < 0.001) in groups A and B, respectively, whereas diuretics, digitalis, and nitrates were more commonly used in octogenarians. CONCLUSION: Preserved systolic function, multiple co-morbidities, and high mortality are observed in octogenarians with HF. In these patients, cardiac function is assessed in only a minority and treatments known to improve prognosis in younger patients under-utilized. Overall, the management of octogenarians with HF does not follow international guidelines.

Adrenergic beta-Antagonists↗
PubMed1992

Relative efficacy of angiotensin converting enzyme inhibitors on mortality of patients with congestive heart failure: implications of randomized trials and role of the aetiology (ischaemic or non-ischaemic) of heart failure.

We examined the influence of angiotensin converting enzyme inhibitors (ACE inhibitors) on mortality in patients with heart failure of both ischaemic or non-ischaemic origin. Eleven, randomized, placebo-controlled trials of ACE inhibitors involving 1266 patients were selected. The follow-up period varied from 3 to 6 months. Four different ACE inhibitors were used in the 11 clinical trials. A total of 679 patients presented with an ischaemic heart failure and 587 with a non-ischaemic heart failure. Meta-analysis, performed for both subgroups, showed that mortality was significantly decreased in the ischaemic subgroup only (ischaemic group: odds ratio 0.45; 95% confidence interval 0.28 to 0.71; non-ischaemic subgroup: odds ratio 0.7; 95% confidence interval 0.4 to 1.5). Although the two odds ratio are not significantly different, further randomized, placebo-controlled trials with ACE inhibitors are required in order to determine more precisely the benefit/risk ratio in patients with non-ischaemic heart failure.

Angiotensin-Converting Enzyme Inhibitors↗
PubMedDate not supplied

The surgical treatment of heart failure. A new frontier: nontransplant surgical alternatives in heart failure.

Heart failure may affect 500,000 new people each year. Heart transplantation has leveled off at approximately 2,500-3,000 cases per year in the United States. Thus, new nontransplant surgical alternatives may be necessary to treat many of the patients who progress to intractable Class III, or especially Class IV heart failure. In addition to left ventricular assist devices, other operations have been used and are now being developed for this purpose. These include left ventricular resection (Batista operation), mitral valve repair, autologous skeletal muscle cardiac assist, splint and compression devices, as well as left ventricular reconstruction by the Dor procedure. All of these procedures have been, and are currently being, evaluated for the surgical treatment of congestive heart failure and they will be reviewed in this article. Although many appear very promising, ongoing trials and retrospective reviews will be increasingly necessary to vigorously define which of the nontransplant surgical alternatives are the best procedures going forward for the large numbers of patients with congestive failure.

Animals↗
PubMed2001

The influence of dose of angiotensin I-converting enzyme inhibitor on systolic blood pressure variability in heart failure: a substudy of the Assessment of Treatment with Lisinopril and Survival in heart failure (ATLAS) trial.

UNLABELLED: Heart failure is associated with a decreased variability in circadian systolic blood pressure. ACE inhibitors have been shown to be beneficial in CHF. However, the effect of the magnitude of the dose of ACE inhibitor on blood pressure variability has not been reported. The objective of this sub-study of the ATLAS trial was to determine if there was a difference in effect on systolic blood pressure variability of two doses (35mg, 'high'; and, 5mg, 'low') of the ACE inhibitor, lisinopril, in patients with heart failure (class II-IV; NYHA). Criteria for inclusion were: symptomatic heart failure (class II-IV; NYHA), left ventricular ejection fraction < or = 30%, and 2 months of conventional therapy with diuretics with, or without, digoxin. Twenty-four hour ambulatory blood pressure was recorded prior to randomization and after peak titration (4 weeks) of the study drug for analysis of variability of systolic blood pressure variability. The high dose of lisinopril was associated with greater variability of 24 h systolic blood pressure as noted by inspection of the 24 h recordings or calculation of the blood pressure variability index (P < 0.05). The greater variability in SBP was not associated with a difference in mean 24 h arterial blood pressure. CONCLUSIONS: Variation in circadian systolic blood pressure is useful in reflecting the influence of the magnitude of dose of the ACE inhibitor lisinopril on the pharmacodynamics of patients with heart failure.

Angiotensin-Converting Enzyme Inhibitors↗
PubMedDate not supplied

Congestive heart failure and continuous positive airway pressure therapy: support of a new modality for improving the prognosis and survival of patients with advanced congestive heart failure.

Nasal continuous positive airway pressure therapy has recently been studied as a nonpharmacologic adjunct to congestive heart failure therapy. In patients with congestive heart failure, it was reported that continuous positive airway pressure therapy for the condition Cheyne-Stokes respiration with central sleep apnea led to long-term improvements in cardiac function and alleviation of heart failure symptoms. Cheyne-Stokes respiration with central sleep apnea is a frequent breathing disorder well described in patients with congestive heart failure, and is an associated risk factor for increased cardiovascular morbidity and mortality. These apneas cause an increase in sympathetic nervous system activity, which would maintain afterload at a high level or tend to increase it with time, leading to further compromise of ejection fraction. Continuous positive airway pressure appears to benefit the failing heart by increasing intrathoracic pressure, which is believed to cause an increase in cardiac output by decreasing the pressure gradient across the heart wall and allowing the left-ventricular end diastolic volume to decrease, thereby reducing the afterload. This beneficial "resting" of the heart has been documented to increase left-ventricular ejection fraction, increase cardiac index, improve inspiratory muscle strength, lower blood pressure and heart rate, decrease plasma and overnight urinary levels of norepinephrine, lower levels of atrial natriuretic peptide and endothelin-1, and increase heart rate variability. Other benefits include improvement in New York Heart Association functional class status and improvement in dyspnea.

Adult↗
PubMed1996

Failure of dental bridges. II. Prevalence of failure and its relation to place of construction.

In this investigation 156 dental bridges, constructed for 132 individuals, were evaluated. The bridges inserted at the College of Dentistry, King Saud University (KSU), Saudi Arabia, were compared with those placed in general dental practice. The results revealed that the rate of bridge failure averaged 35.5%. This was made up from failure of bridges inserted at KSU at (15.4%) and those in general dental practice (46.2%). The major reasons for failure revealed by this study were periodontal disease (36.6%) and secondary caries (23.2%). The average lifespan for the bridges was 6.1 years with 4.5 years for the unfailed bridges. The most commonly used material for bridges was metal-ceramics. The most commonly used pontic design was the modified ridge lap (50.8%), but the saddle type accounted for the greatest percentage of failures (59.6%).

Acrylic Resins↗
PubMed1999

Improving outcomes in congestive heart failure: Val-HeFT. Valsartan in Heart Failure Trial.

The aims of the treatment of heart failure are to improve the quality of life and slow the progression of cardiac disease. Improvement of quality of life is best assessed by questionnaire; progression of the disease is assessed by measuring mortality and morbidity. The agenda for the future is to establish intermediate markers for progression of cardiac disease that can be substituted for morbidity and mortality, and thus improve the efficiency and shorten the follow-up of clinical trials. At present, polypharmacy is required to achieve optimal improvements in quality and duration of life. Furthermore, some drugs may favorably affect one end point and adversely affect the other; for example, beta-blockers may exert adverse short-term effects on quality of life but may slow progression of the disease. Certain inotropic drugs may reduce symptoms but shorten life expectancy. Angiotensin-converting enzyme (ACE) inhibitors have exerted favorable effects on both quality of life and mortality, but the magnitude of these benefits has been disappointingly small. Persistent angiotensin-induced vasoconstriction and endocrine effects, despite ACE inhibition, is one possible explanation. The Valsartan in Heart Failure Trial (Val-HeFT) has been designed to test the efficacy and safety of the AT(1) receptor blocker (ARB) valsartan in combination with ACE inhibitors and all other prescribed therapies in patients with heart failure. The study is powered to detect a mortality benefit and should therefore establish the role of ARBs in this patient group. When this trial and other ongoing studies are completed, we will be more able to define the role of ARBs in the treatment of heart failure.

Angiotensin II↗
PubMed2004

The interaction between heart failure, renal failure and anemia - the cardio-renal anemia syndrome.

BACKGROUND: Many patients with congestive heart failure (CHF) have chronic kidney insufficiency (CKI) and anemia. AIMS: The purpose of this review is to clarify the relationship between these three factors and to study the effect of correction of anemia in CHF and CKI. FINDINGS: Anemia, CHF and CKI are each capable of causing or worsening each other. Thus they form a vicious circle which can result in progressive CHF, CKI and anemia. Aggressive therapy of CHF, CKI and control of the associated anemia with erythropoietin and i.v. iron can prevent the progression of CHF and CKI, reduce hospitalization, and improve quality of life. CONCLUSION: CHF patients are a major source of end-stage renal failure patients and deserve special attention. If treated well and early, progressive heart failure and renal failure can be prevented. Cooperation between nephrologists, cardiologists, and other internists will improve the care of all three conditions and prevent their progression.

Anemia↗
PubMed2005

Lower serum sodium is associated with increased short-term mortality in hospitalized patients with worsening heart failure: results from the Outcomes of a Prospective Trial of Intravenous Milrinone for Exacerbations of Chronic Heart Failure (OPTIME-CHF) study.

BACKGROUND: The prognostic value of serum sodium in patients hospitalized for worsening heart failure has not been well defined. METHODS AND RESULTS: The Outcomes of a Prospective Trial of Intravenous Milrinone for Exacerbations of Chronic Heart Failure (OPTIME-CHF) study randomized 949 patients with systolic dysfunction hospitalized for worsening heart failure to receive 48 to 72 hours of intravenous milrinone or placebo in addition to standard therapy. In a retrospective analysis, we investigated the relationship between admission serum sodium and the primary end point of days hospitalized for cardiovascular causes within 60 days of randomization, as well as the secondary end points of in-hospital mortality, 60-day mortality, and 60-day mortality/rehospitalization. The number of days hospitalized for cardiovascular causes was higher in the lowest sodium quartile: 8.0 (4.5, 18.5) versus 6 (4, 13) versus 6 (4, 11.5) versus 6 (4, 12) days (P<0.015 for comparison with the lowest quartile). Lower serum sodium was associated with higher in-hospital and 60-day mortality: 5.9% versus 1% versus 2.3% versus 2.3% (P<0.015) and 15.9% versus 6.4% versus 7.8% versus 7% (P=0.002), respectively. There was a trend toward higher mortality/rehospitalization for patients who were in the lowest sodium quartile. Multivariable-adjusted Cox proportional hazards analysis showed that serum sodium on admission, when modeled linearly, predicted increased 60-day mortality: sodium (per 3-mEq/L decrease) had a hazard ratio of 1.18 with a 95% CI of 1.03 to 1.36 (P=0.018). CONCLUSIONS: In patients hospitalized for worsening heart failure, admission serum sodium is an independent predictor of increased number of days hospitalized for cardiovascular causes and increased mortality within 60 days of discharge.

Aged↗
PubMed1997

Effect of the calcium antagonist felodipine as supplementary vasodilator therapy in patients with chronic heart failure treated with enalapril: V-HeFT III. Vasodilator-Heart Failure Trial (V-HeFT) Study Group.

BACKGROUND: Despite therapy with diuretics, ACE inhibitors and digoxin morbidity and mortality in heart failure remain high and might respond favorably to an additional vasodilator. METHODS AND RESULTS: Male patients (n=450) with chronic heart failure (cardiac dysfunction and impaired exercise performance) on optimal current therapy (97% enalapril, 89% diuretics) were randomly assigned to double-blind treatment with felodipine extended release (5 mg BID) or placebo for 3 to 39 months (average, 18 months). Felodipine significantly reduced blood pressure and, at 3 months, increased ejection fraction (2.1% versus -0.1% units in the placebo group, P=.001) and reduced plasma atrial natriuretic peptide levels (-2.9 versus 26.9 pg/mL in the placebo group, P=.01) but did not improve exercise tolerance, quality of life, or the need for hospitalization. During long-term follow-up, the favorable effects on ejection fraction and atrial peptide did not persist, but felodipine prevented worsening exercise tolerance and quality of life. In the felodipine and placebo groups, mortality (13.8% versus 12.8%, respectively) and hospitalization (43% versus 42%) rates were similar, and a higher incidence of peripheral edema was the only apparent side effect of felodipine therapy. CONCLUSIONS: Felodipine exerts a well-tolerated additional sustained vasodilator effect in patients with heart failure treated with enalapril, but the only possible long-term benefit was a trend for better exercise tolerance and less depression of quality of life in the second year of treatment. The drug appears to be safe but not clearly efficacious in patients with heart failure.

Adult↗
PubMed2006

Clinical correlates and consequences of anemia in a broad spectrum of patients with heart failure: results of the Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity (CHARM) Program.

BACKGROUND: We wished to determine the prevalence of, potential mechanistic associations of, and clinical outcomes related to anemia in patients with heart failure and a broad spectrum of left ventricular ejection fraction (LVEF). METHODS AND RESULTS: In multivariable analyses, we examined the associations between hemoglobin and baseline characteristics, laboratory variables, and outcomes in 2653 patients randomized in the CHARM Program in the United States and Canada. Anemia was equally common in patients with preserved (27%) and reduced (25%) LVEF but was more common in black and older patients. Anemia was associated with ethnicity, diabetes, low body mass index, higher systolic and lower diastolic blood pressure, and recent heart failure hospitalization. More than 50% of anemic patients had a glomerular filtration rate <60 mL.min(-1).1.73 m(-2) compared with <30% of nonanemic patients. Despite an inverse relationship between hemoglobin and LVEF, anemia was associated with an increased risk of death and hospitalization, a relationship observed in patients with both reduced and preserved LVEF. There were 133 versus 69 deaths and 527 versus 352 hospitalizations per 1000 patient-years of follow-up in anemic versus nonanemic patients (both P<0.001). The effect of candesartan in reducing outcomes was independent of hemoglobin. CONCLUSIONS: Anemia was common in heart failure, regardless of LVEF. Lower hemoglobin was associated with higher LVEF yet was an independent predictor of adverse mortality and morbidity outcomes. In heart failure, the causes of anemia and the associations between anemia and outcomes are probably multiple and complex.

Aged↗
PubMedDate not supplied

Demographics, treatment regimens and the use of angiotensin-receptor blockers in heart failure: findings from the Valsartan Heart Failure Trial.

Heart failure is the only major cardiovascular disease with an incidence and prevalence that continue to increase in the developed world. Early identification and correct treatment of the condition are of paramount importance. In recent years, there has been growing interest in identifying the differences between patients in terms of their risk of heart failure and response to treatment. Differences between men and women, different age groups, patients with varying aetiologies or comorbidities and differences between ethnic groups are only some of the factors that have been identified. This review surveys the available data on differences in responses to treatment, and discusses the use of angiotensin-receptor blockers in heart failure in light of the recent Valsartan Heart Failure Trial (Val-HeFT).

Age Factors↗
PubMed2006

Arterial steroid injection therapy can inhibit the progression of severe acute hepatic failure toward fulminant liver failure.

AIM: To utilize transcatheter arterial steroid injection therapy (TASIT) via the hepatic artery to reduce hepatic macrophage activity in patients with severe acute hepatic failure. METHODS: Thirty-four patients with severe acute hepatic failure were admitted to our hospital between June 2002 to June 2006 providing for the possibility of liver transplantation (LT). Seventeen patients were treated using traditional liver supportive procedures, and the other 17 patients additionally underwent TASIT with 1000 mg methylprednisolone per day for 3 continuous days. RESULTS: Of the 17 patients who received TASIT, 13 were cured without any complications, 2 died, and 2 underwent LT. Of the 17 patients who did not receive TASIT, 4 were self-limiting, 7 died, and 6 underwent LT. Univariate logistic analysis revealed that ascites, serum albumin, prothrombin time, platelet count, and TASIT were significant variables for predicating the prognosis. Multivariate logistic regression analysis using stepwise variable selection showed that prothrombin time, platelet count, and TASIT were independent predictive factors. CONCLUSION: TASIT might effectively prevent the progression of severe acute hepatic failure to a fatal stage of fulminant liver failure.

Adult↗
PubMed1999

Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF)

BACKGROUND: Metoprolol can improve haemodynamics in chronic heart failure, but survival benefit has not been proven. We investigated whether metoprolol controlled release/extended release (CR/XL) once daily, in addition to standard therapy, would lower mortality in patients with decreased ejection fraction and symptoms of heart failure. METHODS: We enrolled 3991 patients with chronic heart failure in New York Heart Association (NYHA) functional class II-IV and with ejection fraction of 0.40 or less, stabilised with optimum standard therapy, in a double-blind randomised controlled study. Randomisation was preceded by a 2-week single-blind placebo run-in period. 1990 patients were randomly assigned metoprolol CR/XL 12.5 mg (NYHA III-IV) or 25.0 mg once daily (NYHA II) and 2001 were assigned placebo. The target dose was 200 mg once daily and doses were up-titrated over 8 weeks. Our primary endpoint was all-cause mortality, analysed by intention to treat. FINDINGS: The study was stopped early on the recommendation of the independent safety committee. Mean follow-up time was 1 year. All-cause mortality was lower in the metoprolol CR/XL group than in the placebo group (145 [7.2%, per patient-year of follow-up]) vs 217 deaths [11.0%], relative risk 0.66 [95% CI 0.53-0.81]; p=0.00009 or adjusted for interim analyses p=0.0062). There were fewer sudden deaths in the metoprolol CR/XL group than in the placebo group (79 vs 132, 0.59 [0.45-0.78]; p=0.0002) and deaths from worsening heart failure (30 vs 58, 0.51 [0.33-0.79]; p=0.0023). INTERPRETATION: Metoprolol CR/XL once daily in addition to optimum standard therapy improved survival. The drug was well tolerated.

Adrenergic beta-Antagonists↗