Clinical Effects of Initial 6 Months Monotherapy with Bisoprolol versus Enalapril in the Treatment of Patients with Mild to Moderate Chronic Heart Failure. Data from the CIBIS III Trial

PURPOSE: To assess the clinical effects and safety profile of initial monotherapy with either bisoprolol or enalapril in elderly patients with heart failure (HF). METHODS: In CIBIS III, 1010 patients with mild to moderate HF and age>or=65 years were randomized to monotherapy with either bisoprolol or enalapril for 6 months. RESULTS: Bisoprolol had a similar effect as enalapril on the combined end-point of all-cause mortality or hospitalization (HR 1.02; p=0.90), as well as on each of the individual end-points. A trend towards fewer sudden deaths was observed with bisoprolol (NS). On the other hand, more cases of worsening HF requiring hospitalization or occurring while in hospital were observed in the bisoprolol group (HR 1.67; p=0.03). The two groups were similar with regard to treatment cessations and early introduction of the second drug. CONCLUSIONS: Bisoprolol and enalapril had a similar effect on the combined end-point of mortality or hospitalization during 6 months monotherapy. However, more worsening HF events were observed in the bisoprolol group.     

Comparative Dose Titration Responses to the Introduction of Bisoprolol or Carvedilol in Stable Chronic Systolic Heart Failure

Introduction Several beta blocking drugs (BB) reduce mortality in systolic heart failure (LVSD). We have compared the initial response to introduction of carvedilol and bisoprolol during the standard dose titration protocols for each drug. Methods Approximately 31 unselected patients with stable LVSD were randomised to either carvedilol or bisoprolol measuring blood pressure, heart rate responses and both time and frequency domain heart rate variability (HRV). Results One subject died; five withdrew due to intolerable BB related side effects. Carvedilol (n = 13) and bisoprolol (n = 12) attained similar maximal heart rate reduction and induced comparable falls in systolic and diastolic blood pressure. Higher carvedilol doses were associated with lower blood pressure compared to baseline. Individual time domain HRV indices remained unchanged over the initial titration period. Significant increases in triangular Index (TI) were seen with both BB. Carvedilol demonstrated greater (but non-significant) rises in TI compared to Bisoprolol. Conclusions In this study we found similar degrees and rate of onset of HR, HRV and BP response to both carvedilol and bisoprolol in treated LVSD patients. Carvedilol appears to show superior HRV rises compared to bisoprolol during initial titration. Any significant increases in HRV attributable to carvedilol compared to bisoprolol may emerge over a longer treatment interval in LVSD.     

Cost‐Effectiveness of Remote Cardiac Monitoring With the CardioMEMS Heart Failure System

Heart failure (HF ) is a leading cause of cardiovascular mortality in the United States and presents a substantial economic burden. A recently approved implantable wireless pulmonary artery pressure remote monitor, the CardioMEMS HF System, has been shown to be effective in reducing hospitalizations among New York Heart Association (NYHA ) class III HF patients. The objective of this study was to estimate the cost‐effectiveness of this remote monitoring technology compared to standard of care treatment for HF . A Markov cohort model relying on the CHAMPION (CardioMEMS Heart Sensor Allows Monitoring of Pressure to Improve Outcomes in NYHA Class III Heart Failure Patients) clinical trial for mortality and hospitalization data, published sources for cost data, and a mix of CHAMPION data and published sources for utility data, was developed. The model compares outcomes over 5 years for implanted vs standard of care patients, allowing patients to accrue costs and utilities while they remain alive. Sensitivity analyses explored uncertainty in input parameters. The CardioMEMS HF System was found to be cost‐effective, with an incremental cost‐effectiveness ratio of $44,832 per quality‐adjusted life year (QALY ). Sensitivity analysis found the model was sensitive to the device cost and to whether mortality benefits were sustained, although there were no scenarios in which the cost/QALY exceeded $100,000. Compared with standard of care, the CardioMEMS HF System was cost‐effective when leveraging trial data to populate the model.     

Congestive Heart Failure and Genomic Medicine: A Look into the 21st Century

Congestive heart failure (CHF) has emerged as one of the leadingcardiovascular disorders in developed countries, as indicated by theprevalence of the disease; the incidence of hospitalization, morbidity, andmortality; and its global economic burden. Furthermore, it is expected thatheart failure and other cardiovascular disorders will become the majordisease burdens in developing countries by the year 2020. It is wellestablished that pharmacological therapy of CHF, although still notoptimum, improves patient quality of life and reduces morbidity andmortality. However, CHF remains a relentlessly progressive disease. In thisbrief review an attempt is made to explore the contemporary,state-of-the-art pharmacological approach to the treatment of heartfailure, the unmet medical need that still remains, and the potentialimpact of genomic medicine on the treatment of heart failure in the 21stcentury.     

芪参益气汤联合比索洛尔对老年慢性心力衰竭病人BNP及心功能的影响

目的探讨芪参益气汤联合比索洛尔对老年慢性心力衰竭病人血浆脑钠肽(BNP)及心功能的影响。方法将2016年4月—2018年1月我院78例老年慢性心力衰竭病人,随机分为观察组与对照组,每组39例。对照组采用比索洛尔2.5~10.0mg口服;观察组采用比索洛尔2.5~10.0mg口服联合芪参益气汤治疗,持续治疗8周。比较两组临床疗效、左室舒张末期内径(LVEDD)、左室收缩末期内径(LVESD)、左室射血分数(LVEF)及BNP、肌钙蛋白I(cTnI)水平,记录不良反应情况。结果对照组有效率为74.36%,低于观察组的92.31%,差异有统计学意义(P<0.05)。治疗后两组LVEDD、LVESD、LVEF、BNP及cTnI比较差异均有统计学意义(P<0.05)。对照组不良反应发生率为12.82%,观察组不良反应发生率为17.95%,差异无统计学意义(P>0.05)。结论芪参益气汤联合比索洛尔对老年慢性心力衰竭病人疗效确切,有助于降低血浆BNP,改善心功能,且安全性较高。     

双室起搏治疗充血性心力衰竭近期疗效研究

为进一步观察双室起搏对充血性心力衰竭 (简称心衰 )治疗的效果 ,对 10例充血性心衰病人置入InSync(三腔 )起搏器 ,并观察术前及术后 3个月临床症状及心功能指标的情况。结果 :置入起搏器术后 3个月 ,心功能明显改善 ,从 3.4 4± 0 .5 2级降至 1.5 0± 0 .72级 (P <0 .0 1) ,心衰症状评分从 8.1± 3.2 9分降至 1.4± 1.74分 (P <0 .0 1) ,左室舒张末期内径从 6 7± 6 .6 8mm减至 6 2 .75± 5 .92mm(P <0 .0 5 ) ,射血分数从 0 .35± 0 .0 7增至 0 .4 3± 0 .10 (P <0 .0 5 )。结论 :双室起搏治疗可明显改善心功能 ,提高病人生活质量 ,逆转左室重塑。     

The effects of beta-blockers on morbidity and mortality in a population-based cohort of 11,942 elderly patients with heart failure

PURPOSE: Randomized trials have shown that beta-blockers prevent morbidity and mortality in heart failure. However, whether beta-blockers are effective in older patients or those with conditions that would have led to their exclusion from these trials remains unclear. SUBJECTS AND METHODS: The associations between beta-blocker use and outcomes were examined in a population-based cohort of 11,942 older (age >/=65 years) patients with incident heart failure between 1994 and 1999. Cox proportional hazards models were used to adjust for propensity scores, age, sex, comorbid conditions, and other medications. RESULTS: The mean (+/- SD) age of the patients was 79 +/- 8 years, 5819 (49%) were men, and 2569 (22%) had Charlson comorbidity scores of at least 2. During follow-up (median, 21 months), 3539 patients were hospitalized for heart failure and 6757 died. Overall, 1162 patients received beta-blockers. After adjustment, beta-blocker use was associated with substantial reductions in all-cause mortality (hazard ratio [HR] = 0.72; 95% confidence interval [CI]: 0.65 to 0.80), mortality due to heart failure (HR = 0.65; 95% CI: 0.47 to 0.90), and hospitalizations for heart failure (HR = 0.82; 95% CI: 0.74 to 0.92). These endpoints were less frequent in patients treated with beta-blockers than in untreated patients in all examined subgroups. All doses of beta-blockers were associated with benefit, but there was a trend towards greater benefit in patients prescribed higher doses. CONCLUSIONS: The benefits of beta-blockers seen in randomized trials extend to older patients and to those with conditions that would have led to their exclusion from the trials. There is a need for a randomized trial comparing different doses of beta-blockers in heart failure.     

Stem Cell Therapy in Patients with Heart Failure

Heart failure results from injury to the myocardium from a variety of causes, including ischemic and nonischemic etiologies. Severe heart failure carries a 50% 5-year mortality rate and is responsible for more than one-third of cardiovascular deaths in the United States.1 Heart failure progression is accompanied by activation of neurohormonal and cytokine systems as well as a series of adaptive changes within the myocardium, collectively referred to as left ventricular remodelling. The unfavorable alterations may be categorized broadly into changes that occur in the cardiac myocytes and changes that occur in the volume and composition of the extracellular matrix.2 Since remodelling in heart failure is progressive and eventually becomes detrimental, the majority of treatment strategies are aimed at stopping or reversing this process. Although medical management, cardiac resychronization therapy, and long-term or destination mechanical circulatory support have been successful in this regard, a considerable number of patients still progress to end-stage heart failure with limited therapeutic options. For these patients, stem cell therapies are being investigated as a safe treatment strategy for decreasing cardiac remodelling on top of conventional medical and device treatment.     

Evolution of Biomarker Guided Therapy for Heart Failure: Current Concepts and Trial Evidence

Optimizing management of patients with heart failure remains quite challenging despite many significant advances in drug and device therapy for this syndrome. Although a large body of evidence from robust clinical trials supports multiple thera-pies, utilization of these well-established treatments remains inconsistent and outcomes suboptimal in “real-world” patients with heart failure. Disease management programs may be effective, but are difficult to implement due to cost and logistical issues. Another approach to optimizing therapy is to utilize biomarkers to guide therapeutic choices. Natriuretic peptides pro-vide additional information of significant clinical value in the diagnosis and estimation of risk inpatients with heart failure. Ongoing research suggests a potential important added role for natriuretic peptides in heart failure. Guiding therapy based on serial changes in these biomarkers may be an effective strategy to optimize treatment and achieve better outcomes in this syn-drome. Initial, innovative, proof-of-concept studies have provided encouraging results and important insights into key as-pects of this strategy, but well designed, large-scale, multicenter, randomized, outcome trials are needed to definitively estab-lish this novel approach to management. Given the immense and growing public health burden of heart failure, identification of cost-effective ways to decrease the morbidity and mortality due to this syndrome is critical.     

Beta-Blocker Efficacy According to Heart Rate and Rhythm in Patients with Heart Failure. Commentary on the Cardiac Insufficiency Bisoprolol Study II Analysis

Large randomized trials have demonstrated that beta-blocker treatment reduces morbidity and mortality in patients in chronic heart failure. Questions remain about the influence of individual characteristics on the magnitude of the benefit of beta-blockers in patients with heart failure including the influence of heart rate and cardiac rhythm. In the Cardiac Insufficiency Bisoprolol Study II, baseline heart rate and heart rate change over time had prognostic value but treatment with bisoprolol was associated with a benefit at all levels of baseline heart rate and additional benefit related to heart rate slowing was observed. In the subgroup of patients with atrial fibrillation, morbidity and mortality rates were similar in placebo and bisoprolol treated patients. It is possible that patients with atrial fibrillation had a higher level of sympathetic stimulation that would have required higher doses of bisoprolol to achieve a similar level of beta-blockade. Alternatively, the failure to observe improved outcome in the subgroup with atrial fibrillation may have been due to chance. However, because this finding was not observed in other large trials, and because there was no clear explanation, it should not be concluded that patients with chronic heart failure and atrial fibrillation do not benefit from beta-blockade.     

慢性心力衰竭的非药物治疗进展

慢性心力衰竭在常规药物治疗的基础上,非药物治疗可进一步改善病人的预后.心脏再同步化治疗、埋藏式心脏复律除颤器及心脏机械辅助装置等慢性心力衰竭器械治疗发展迅速,基因、干细胞移植及植物神经干预等非药物治疗方法也不断在探索中前进.     

Prediction of the Effect of Bisoprolol in Dilated Cardiomyopathy

Survival improvement by beta-blocker treatment in patients with chronic heart failure appears to be related to the intermediate-term changes in left ventricular function. The therapeutic potential of beta blockade might be increased by early identification of patients in whom left ventricular function would deteriorate. We aimed at predicting the intermediate-term effect of bisoprolol on left ventricular systolic and diastolic function in patients with dilated cardiomyopathy. Twenty-five patients with symptomatic chronic heart failure treated with bisoprolol were investigated. As a background, tailored therapy with digitalis, diuretics and vasodilators was given. Prediction of the 6-month (intermediate-term) effect of bisoprolol was investigated, using baseline values and short-term (1-month) changes of simple, noninvasive parameters obtained at rest and during maximal exercise. Multivariate analysis resulted in reliable predictions, there was close correlation between the observed and predicted changes of left atrial filling pressure (R = 0.87) and left ventricular ejection fraction (R = 0.74). The baseline value of left ventricular ejection fraction, short-term changes of the pulse amplitude and the double product proved independent predictors of intermediate-term changes of left ventricular ejection fraction. The baseline value of mean pulmonary capillary wedge pressure, heart rate, and increase in heart rate during maximal exercise were predictors of the intermediate-term changes in mean pulmonary capillary wedge pressure. In dilated cardiomyopathy, the intermediate-term effects of bisoprolol on left ventricular ejection fraction and mean pulmonary capillary wedge pressure can be predicted reliably by simple noninvasive variables in the early treatment phase.     

Effect on Mode of Death of Heart Failure Treatment Started with Bisoprolol Followed by Enalapril,Compared to the Opposite Order: Results of the Randomized CIBIS III Trial

Background: Mode of death in chronic heart failure (CHF) may be of relevance to choice of therapy for this condition. Sudden death is particularly common in patients with early and/or mild/moderate CHF. β‐Blockade may provide better protection against sudden death than ACE inhibition (ACEI) in this setting. Methods: We randomized 1010 patients with mild or moderate, stable CHF and left ventricular ejection fraction ≤35%, without ACEI, β‐blocker or angiotensin‐receptor‐blocker therapy, to either bisoprolol (n = 505) or enalapril (n = 505) for 6 months, followed by their combination for 6–24 months. The two strategies were blindly compared regarding adjudicated mode of death, including sudden death and progressive pump failure death. Results: During the monotherapy phase, 8 of 23 deaths in the bisoprolol‐first group were sudden, compared to 16 of 32 in the enalapril‐first group: hazard ratio (HR) for sudden death 0.50; 95% confidence interval (CI) 0.21–1.16; P= 0.107. At 1 year, 16 of 42 versus 29 of 60 deaths were sudden: HR 0.54; 95% CI 0.29–1.00; P= 0.049. At study end, 29 of 65 versus 34 of 73 deaths were sudden: HR 0.84; 95% CI 0.51–1.38; P= 0.487. Comparable figures for pump failure death were: monotherapy, 7 of 23 deaths versus 2 of 32: HR 3.43; 95% CI 0.71–16.53; P= 0.124, at 1 year, 13 of 42 versus 5 of 60: HR 2.57; 95% CI 0.92–7.20; P= 0.073, at study end, 17 of 65 versus 7 of 73: HR 2.39; 95% CI 0.99–5.75; P= 0.053. There were no significant between‐group differences in any other fatal events. Conclusion: Initiating therapy with bisoprolol compared to enalapril decreased the risk of sudden death during the first year in this mild systolic CHF cohort. This was somewhat offset by an increase in pump failure deaths in the bisoprolol‐first cohort.     

他汀类药物治疗慢性心力衰竭的研究进展

临床研究已证实他汀在冠心病治疗中的价值,至少已在无心力衰竭的冠心病患者中得以明确.因此他汀可能对慢性心力衰竭具有很大的潜在价值,尤其对冠心病性心力衰竭.现综述他汀治疗慢性心力衰竭的研究进展.     

Beta Blocker Therapy in African American Patients with Heart Failure

Data from a number of clinical trials of beta blocker therapy in heart failure, although limited in the size of African American patients included, suggest that they achieve a similar benefit as Caucasians. African Americans were usually at higher risk when enrolled in all of these studies with a higher incidence of hypertension and diabetes mellitus. The only exception is the Beta Blocker Evaluation of Survival Trial (BEST) that studied the efficacy of Bucindolol in heart failure. In that study there appeared to be a unique differential effect in African Americans compared to Caucasians which may have been in part related to the severity of the disease.     

Results from post-hoc analyses of the CIBIS II trial: effect of bisoprolol in high-risk patient groups with chronic heart failure

BACKGROUND: The beneficial effects of the beta-blocker bisoprolol on mortality and rate of hospitalisation as well as its safety in patients with chronic heart failure has been proven. However, its efficacy in patients in whom beta-blockers have traditionally been contraindicated or caution has been advised has not been clearly determined. Therefore, analyses in high-risk subgroups of patients taking part in CIBIS II have been performed to investigate the effect of bisoprolol in elderly patients, in patients with type 2 diabetes, with renal failure, NYHA functional class IV or concomitantly treated with digitalis, aldosterone antagonists or amiodarone. METHODS: High-risk subgroups of patients with chronic heart failure taking part in the CIBIS II study were retrospectively analysed with respect to mortality, hospitalisation, combined endpoint of cardiovascular mortality or hospitalisation for cardiovascular reasons and treatment withdrawal as well as cause of death and hospitalisation. Analysis is based on intention-to-treat. RESULTS: It was demonstrated that in spite of the expected increase in the overall risk of death and hospitalisation, patients who are diabetic, have renal impairment, NYHA class IV symptoms, are elderly, are taking either digitalis, amiodarone or aldosterone antagonists as co-medication benefit equally from beta-blockade with bisoprolol as patients without these complications or drugs. Benefit was shown for the primary endpoint all cause mortality, as well as for the secondary endpoints. CONCLUSIONS: Contrary to the hitherto prevailing doctrine of not using beta-blockers in high risk patient groups with chronic heart failure, retrospective analyses of the CIBIS II study justify the use of this drug class in patients regardless of age, NYHA functional class, the presence of diabetes, renal impairment or concomitant treatment with digitalis, amiodarone or aldosterone antagonists.     

Heart Failure Therapy at the Turn of the Century

Major changes in the treatment of heart failure have occurred in the last fifty years that have had a dramatic effect on its morbidity and mortality. Over two hundred years have passed since the demonstration of the benefit of digitalis in heart failure to the development of potent loop diuretics. The observation that vasodilators could improve both cardiac function and mortality led to the investigation of the Angiotensin Converting Enzyme Inhibitors (ACEI). Although these agents had significant vasodilator properties, their major benefit appears to be related to their ability to effect remodeling of the failing left ventricle. The most recent randomized clinical trials demonstrate that Beta Adrenergic Blocking agents can provide an incremental effect on both mortality and morbidity when added to therapy with ACEI. Although these agents have improved the outlook for the heart failure patient, they have had very little effect on the improvement of left ventricular function. Future research must be directed at methods to deal with this issue by either changing the contractile properties of the cardiomyocyte by pharmacologic or electrical therapy or by transplanting functional cells that can increase the number of functioning contractile units.     

抗细胞因子治疗心力衰竭的研究进展

近年来 ,炎性细胞因子在心力衰竭发展中的作用已成为研究热点。有研究证实 ,抗细胞因子治疗可以减缓心力衰竭进程。因此 ,为了明确炎性细胞因子在心力衰竭病理生理发生机制中的作用 ,就以下几个方面作简要介绍 :炎性细胞因子的生物学特性及其对心脏重塑及心力衰竭发生发展的影响 ,目前抗细胞因子治疗心力衰竭策略的现状。