Explore the vast range of titles available.

Background and aimsCarvedilol is effective in the primary prophylaxis for large oesophageal varices. We investigated its use in preventing progression of small to large oesophageal varices.MethodsConsecutive cirrhotics with small oesophageal varices were prospectively randomised to either carvedilol (n=70) or placebo (n=70) and followed up for a minimum of 24 months. Endoscopy was done at baseline and six monthly intervals. Hepatic vein pressure gradient (HVPG) was measured at baseline and at 12 months. The primary endpoint was development of large varices.ResultsBaseline characteristics in two groups were comparable. The predominant aetiology of cirrhosis was non-alcoholic fatty liver disease in both the groups. The mean dose of carvedilol administered was 12±1.67 mg/day and the target heart rate achieved was 58±3 bpm. A higher proportion of patients in carvedilol group had non-progression to large varices than placebo (79.4% vs 61.4%; p=0.04); the mean time of non-progression to large varices was 20.8 months (95% CI 19.4 to 22.4) in carvedilol group and 18.7 months (95% CI 17.1 to 20.4) in placebo group (p=0.04). There was a modest reduction of HVPG at 1 year in carvedilol group (−8.64%) compared with placebo (+0.33%) (p=0.22). None of the patients in either group died of variceal bleeding or liver-related causes. No major adverse events were observed in either group.ConclusionsCarvedilol is safe and effective in delaying the progression of small to large oesophageal varices in patients with cirrhosis.Trial registration numberNCT01196507; post-results.

β blockers reduce mortality in patients who have chronic heart failure, systolic dysfunction, and are on background treatment with diuretics and angiotensin-converting enzyme inhibitors. We aimed to compare the effects of carvedilol and metoprolol on clinical outcome. In a multicentre, double-blind, and randomised parallel group trial, we assigned 1511 patients with chronic heart failure to treatment with carvedilol (target dose 25 mg twice daily) and 1518 to metoprolol (metoprolol tartrate, target dose 50 mg twice daily). Patients were required to have chronic heart failure (NYHA II–IV), previous admission for a cardiovascular reason, an ejection fraction of less than 0·35, and to have been treated optimally with diuretics and angiotensin-converting enzyme inhibitors unless not tolerated. The primary endpoints were all-cause mortality and the composite endpoint of all-cause mortality or all-cause admission. Analysis was done by intention to treat. The mean study duration was 58 months (SD 6). The mean ejection fraction was 0·26 (0·07) and the mean age 62 years (11). The all-cause mortality was 34% (512 of 1511) for carvedilol and 40% (600 of 1518) for metoprolol (hazard ratio 0·83 [95% CI 0·74–0–93], p=0–0017). The reduction of all-cause mortality was consistent across predefined subgroups. The composite endpoint of mortality or all-cause admission occurred in 1116 (74%) of 1511 on carvedilol and in 1160 (76%) of 1518 on metoprolol (0·94 [0·86–1–02], p=0·122). Incidence of side-effects and drug withdrawals did not differ by much between the two study groups. Our results suggest that carvedilol extends survival compared with metoprolol.

As compared with placebo, carvedilol reduced the risk of death by 35 percent and the combined risk of death or hospitalization by 24 percent. Beta-blocking agents have been shown to reduce the risk of hospitalization and death in patients with mild-to-moderate heart failure, 1 – 4 but little is known about the efficacy or safety of these agents in severe heart failure. Earlier large-scale studies with bisoprolol, carvedilol, and metoprolol enrolled primarily patients with New York Heart Association class II or III symptoms, and thus they did not provide meaningful information about the effects of these drugs in patients who have symptoms at rest or on minimal exertion. Only one large-scale study of beta-blockade (with bucindolol) focused on patients with severe heart failure; it did not . . .

In this study of a non-selective beta-blocker, bucindolol, there was no effect of treatment on overall mortality. Beta-blockers have emerged as an important treatment for chronic heart failure. Two recently completed trials, the Metoprolol CR/XL Randomized Intervention Trial in Congestive Heart Failure 1 and the Cardiac Insufficiency Bisoprolol Study II, 2 demonstrated statistically significant and clinically relevant decreases in the rates of hospitalization and death with beta-adrenergic–receptor antagonists in patients with New York Heart Association (NYHA) class II, III, or IV heart failure. However, mortality in the placebo group in these trials was only 11 to 13 percent annually, suggesting that the proportion of high-risk, severely ill patients was low. Furthermore, both studies were performed in largely white European . . .

Background: β Blocker treatment may worsen glucose metabolism. Objective: To study the development of new onset diabetes in a large cohort of patients with heart failure treated with either metoprolol or carvedilol. Design: Prospective and retrospective analysis of a controlled clinical trial. Setting: Multinational multicentre study. Patients: 3029 patients with chronic heart failure. Interventions: Randomly assigned treatment with carvedilol (n = 1511, target dose 50 mg daily) or metoprolol tartrate (n = 1518, target dose 100 mg daily). Results: Diabetic events (diabetic coma, peripheral gangrene, diabetic foot, decreased glucose tolerance or hyperglycaemia) and new onset diabetes (clinical diagnosis, repeated high random glucose level or glucose lowering drugs) were assessed in 2298 patients without diabetes at baseline. Diabetic events occurred in 122/1151 (10.6%) patients in the carvedilol group and 149/1147 (13.0%) patients in the metoprolol group (hazard ratio (HR) = 0.78; 95% confidence interval (CI) 0.61 to 0.99; p = 0.039). New onset diabetes was diagnosed in 119/1151 (10.3%) v 145/1147 (12.6%) cases in the carvedilol and metoprolol treatment groups (HR = 0.78, CI 0.61 to 0.997; p = 0.048), respectively. Patients with diabetes at baseline had an increased mortality compared with non-diabetic subjects (45.3% v 33.9%; HR = 1.45, CI 1.28 to 1.65). Both diabetic and non-diabetic subjects at baseline had a similar reduction in mortality with carvedilol compared with metoprolol (RR = 0.85; CI 0.69 to 1.06 and RR = 0.82; CI 0.71 to 0.94, respectively). Conclusion: A high prevalence and incidence of diabetes is found in patients with heart failure over a course of 5 years. New onset diabetes is more likely to occur during treatment with metoprolol than during treatment with carvedilol.

Background Anthracyclines are widely used in the treatment of childhood cancer. One of the well-recognized side-effects of anthracycline therapy is dose-dependent cardiomyopathy that may progress to heart failure (HF) years after completion of cancer-directed therapy. This study will evaluate the efficacy of low-dose beta-blocker (carvedilol) for HF risk reduction in childhood cancer survivors at highest risk for HF. The proposed intervention has the potential to significantly reduce chronic cardiac injury via interruption of neurohormonal systems responsible for left ventricular (LV) remodeling, resulting in improved cardiac function and decreased risk of HF. The intervention is informed by previous studies demonstrating efficacy in pediatric and adult non-oncology populations, yet remains unstudied in the pediatric oncology population. Methods/Design The primary objective of the trial is to determine impact of the intervention on echocardiographic markers of cardiac remodeling and HF risk, including: LV wall thickness/ dimension ratio (LVWT/D; primary endpoint), as well as LV ejection fraction, volume, and blood biomarkers (natriuretic peptides, galectin-3) associated with HF risk. Secondary objectives are to establish safety and tolerability of the 2-year course of carvedilol using: 1) objective measures: hepatic and cardiovascular toxicity, treatment adherence, and 2) subjective measures: participant self-reported outcomes. Two hundred and fifty survivors of childhood cancer (diagnosed <21 years of age), and previously treated with high-dose (≥300 mg/m 2 ) anthracyclines will be enrolled in a randomized, double-blind, placebo controlled trial. After baseline assessments, participants will be randomized in a 1:1 ratio to low-dose carvedilol (maximum dose: 12.5 mg/day) or placebo. Carvedilol or placebo is up-titrated (starting dose: 3.125 mg/day) according to tolerability. Discussion When completed, this study will provide much-needed information regarding a physiologically plausible pharmacological risk-reduction strategy for childhood cancer survivors at high risk for developing anthracycline-related HF. Trial registration ClinicalTrials.gov; NCT02717507

Heart failure is a substantial public health problem among black Americans. It is more common in the black population than in other populations in the United States, affecting approximately 3 percent of all black adults in this country. 1 , 2 Symptoms of heart failure develop in blacks at an earlier age than they do in nonblacks, 3 – 5 possibly because blacks are more likely to have hypertension and diabetes and to have ventricular hypertrophy and vascular injury than nonblacks. 5 – 8 Once diagnosed, heart failure progresses more rapidly in black patients than in white patients, as evidenced by the higher risk of initial . . .

Objectives: We explored the prescription of β-blockers with ivabradine in patients with systolic heart failure, focusing on the most frequently coprescribed β-blocker, carvedilol. Methods: We analyzed outcomes in SHIFT patients with systolic heart failure who were prescribed β-blockers (carvedilol, bisoprolol, metoprolol, or nebivolol) with ivabradine or placebo. Analysis was by intention to treat in patients prescribed a β-blocker at the time of the event. Results: Data were available for 2,596 patients receiving carvedilol, 1,483 bisoprolol, 1,424 metoprolol, and 197 nebivolol. Mean treatment duration was 19 months. There was no difference in the effect of ivabradine on the primary composite endpoint of cardiovascular death or heart failure hospitalization between the various β-blockers [hazard ratios (HR) for risk reduction, 0.75-0.89; p for interaction = 0.86]. Patients prescribed carvedilol with ivabradine had lower rates of primary composite endpoint (HR 0.80, 95% CI: 0.68-0.94), heart failure hospitalization (HR 0.73, 95% CI: 0.61-0.88), and cardiovascular hospitalization (HR 0.80, 95% CI: 0.69-0.92) versus carvedilol with placebo. The dosage of carvedilol had no detectable effect and there were no unexpected safety issues. Conclusions: Whatever β-blocker was coprescribed with ivabradine, there were improvements in cardiovascular outcomes in patients with systolic heart failure, especially with the most prescribed β-blocker - carvedilol.

Background Heart failure (HF) is a common and disabling condition in older people. Randomized clinical trials and meta-analyses have clearly demonstrated that the long-term use of β-Blockers improves the outcome of patients with HF. However, limited data are available on the treatment of older HF patients with preserved ejection fraction (EF). No study has specifically compared the relative effectiveness of carvedilol and nebivolol in treating HF in older patients with preserved EF. Method/design This trial is a prospective, randomized, open-label, single-centre, active controlled study designed to investigate the effects of nebivolol and carvedilol on diastolic function of the left ventricle (LV) in older HF patients with preserved EF. We will test the hypothesis that nebivolol improves LV diastolic function to a greater extent than carvedilol in patients over 70 years of age. The study population includes 62 older patients newly diagnosed with HF. Patients will be included in the study if they have a LVEF ≥40 %, New York Heart Association (NYHA) functional classes I, II or III status, and have been clinically stable without hospital admission for HF in the preceding 3 months. Eligible patients will be randomly assigned, in a 1:1 ratio, to receive a loading and maintenance dose of either nebivolol or carvedilol. Echocardiographic evaluations will be performed at baseline, 6, and 12 months after therapy. Clinical assessment and laboratory tests are to be performed at fixed times. Discussion This trial is a single-center study that aims to evaluate the impact of nebivolol on LV diastolic function. The results of the study will provide information about the optimal choice of a β-Blocker in the management of patients after diagnosis of HF with preserved EF. The results will be available by 2017. Trial registration ClinicalTrials.gov Identifier: NCT02619526 , registered on 25 November 2015.

Purpose Ischemia/reperfusion injury remains an untreated clinical problem in patients with acute myocardial infarction (AMI) despite significant advances in emergent revascularization through percutaneous coronary intervention (PCI). Pharmacological intervention for infarct size reduction is unavailable. We have identified that the medications milrinone and esmolol, when administered together at the beginning of the reperfusion, significantly decrease infarct size via reducing reperfusion injury in an experimental model. The present study tested the safety of combination therapy of milrinone and esmolol (M + E) in patients with AMI. Methods Sixteen subjects with AMI requiring PCI were consecutively recruited. M + E was intravenously infused simultaneously for 10 min started at 5 min before anticipated angioplasty balloon inflation. Another 16 consecutively recruited AMI patients requiring PCI served as a placebo arm treated per routine clinical protocol. Blood pressure (BP) and heart rate (HR) were monitored continuously during PCI. Results M + E combination therapy resulted in a trend of non-significant reduction in BP compared with a control group. There was a modest but significant increase in HR at the later phase of M + E infusion compared with a control group. No significant cardiac arrhythmia was induced during M + E infusion. Conclusions The combination therapy with M + E produces a minimal change in hemodynamics and appears safe as an adjunctive therapy to PCI in AMI patients. Further studies are warranted.