卡维地洛与美托洛尔治疗慢性充血性心力衰竭的疗效对比

目的比较卡维地洛与美托洛尔治疗慢性充血性心力衰竭的临床疗效。方法将112例慢性充血性心力衰竭患者随机均分成2组,在常规治疗基础上,A组56例口服卡维地洛、B组56例口服美托洛尔,治疗并随访6个月,比较两组患者治疗前后的疗效及超声心动图检查的心功能指标。结果卡维地洛治疗组总有效率为91.07%,美托洛尔治疗组为80.36%,两组比较差异有显著性（P〈0.05）;两组治疗后左心室舒张末期内径（LVEDD）、左心室射血分数（LVEF）均较治疗前显著改善（P〈0.01）,卡维地洛治疗组在减少LVEDD、提高LVEF方面较美托洛尔治疗组更显著（P〈0.05）。结论卡维地洛和美托洛尔都可以有效改善慢性充血性心力衰竭患者的心功能,但卡维地洛的疗效优于美托洛尔。     

beta-blocker use and diabetes symptom score: results from the GEMINI study

AIM: The Glycemic Effect in Diabetes Mellitus: Carvedilol-Metoprolol Comparison in Hypertensives (GEMINI) trial compared the metabolic effects of two beta-blockers in people with type 2 diabetes and hypertension treated with renin-angiotensin system (RAS) blockade and found differences in metabolic outcomes. In this paper, we report the results of a prespecified secondary analysis of GEMINI that sought to determine the effect of these two beta-blockers on commonly reported symptoms. METHODS: The Diabetes Symptom Checklist (DSC), a self-report questionnaire measuring the occurrence and perceived burden of diabetes-related symptoms, was completed by GEMINI participants at baseline and at the end of the study (maintenance month 5). The DSC assessed symptoms in eight domains: psychology (fatigue), psychology (cognitive), neuropathy (pain), neuropathy (sensory), cardiology, ophthalmology, hyperglycaemia and hypoglycaemia. RESULTS: Comparison of the mean change in self-reported diabetes-related symptoms indicated a significant treatment difference favouring carvedilol over metoprolol tartrate in overall symptom score (-0.08; 95% CI -0.15, -0.01; p = 0.02) and in the domains for hypoglycaemia symptoms (-0.12; 95% CI -0.23, -0.02; p = 0.02) and hyperglycaemia symptoms (-0.16; 95% CI -0.27, -0.05; p = 0.005). Carvedilol resulted in fewer perceived diabetes-related symptoms in patients with diabetes and hypertension. CONCLUSION: Carvedilol resulted in a lower perceived burden of diabetes-related symptoms in patients with type 2 diabetes and hypertension. The addition of a well-tolerated beta-blocker to RAS blockade may improve hypertension treatment and quality of life in patients with diabetes.     

Hemodynamic effects of one week of carvedilol administration on cirrhotic rats

Background Carvedilol is a nonselective β-blocker with α₁-adrenergic blocking activity. It has been shown to decrease portal pressure in cirrhotic patients. The current study was undertaken to evaluate the possible mechanism of carvedilol on hemodynamics in cirrhotic rats with portal hypertension produced by common bile duct ligation. Methods Male Sprague-Dawley rats received either a sham operation or common bile duct ligation. Three weeks after surgery, both sham-operated and cirrhotic rats were randomly assigned to receive vehicle or carvedilol 5 mg · kg⁻¹ · 12 h⁻¹ by gastric gavage for 1 week. Hemodynamic measurements, serum biochemistry, serum nitrate/nitrite and 6-keto-PGF_1α levels, and aortic mRNA expression of eNOS and COX-1 were performed on the eighth day after drug administration. Results Carvedilol treatment did not affect serum biochemistry in either sham-operated or cirrhotic rats. In sham-operated rats, administration of carvedilol significantly decreased the heart rate without affecting other hemodynamic values. In contrast, in cirrhotic rats, administration of carvedilol significantly decreased the cardiac index, portal pressure, heart rate, and portal territory blood flow, and it significantly increased systemic and portal territory vascular resistances. The hepatocollateral resistance was significantly decreased, but the hepatic arterial blood showed no significant changes. In sham-operated rats treated with carvedilol, serum nitrate/nitrite and 6-keto-PGF_1α levels were not affected. In contrast, cirrhotic rats receiving carvedilol showed a significant decrease in serum nitrate/nitrite and 6-keto-PGF_1α levels, associated with a decrease in aortic mRNA expression of eNOS and COX-1 compared with those receiving vehicle. Conclusions Carvedilol decreased portal pressure through a reduction of splanchnic blood flow associated with a decrease in hepatocollateral resistance. Additionally, administration of carvedilol decreased endothelial-related vasodilatory activities.     

卡维地洛对尿毒症心肌病患者的疗效观察

目的 探讨卡维地洛对尿毒症心肌病的干预作用.方法 104例尿毒症心肌病患者随机分为两组,每组52例.一组予以常规治疗(对照组),另一组在常规治疗基础上应用卡维地洛12.5～50mg/d(治疗组),总疗程6个月.治疗前后用彩色多普勒检测左室相关数据并测定尿素氮(BUN)、血清肌酐(Set)及内生肌酐清除率(Ccr).结果 与治疗前比较,治疗后两组患者每搏心输出量(SV)、每分心输出量(CO)及射血分数(EF)升高,左室舒张末内径(LVEDD)、室间隔厚度(IVST)、左室后壁厚度(LVPWT)、左室重量(LVM)及左室重量指数(LVMI)下降(P＜0.01),且治疗组疗效明显优于对照组(P＜0.05),Ccr有增加趋势,BUN、Scr有下降趋势,但差异均无统计学意义(P＞0.05).结论 卡维地洛能有效抑制尿毒症心肌病患者的心室重塑,改善心功能及心脏结构,但对肾功能的改善作用不明显.     

New antiarrhythmic treatment of atrial fibrillation

Antiarrhythmic pharmaceutical development for the treatment of atrial fibrillation (AF) is moving in several directions. The efficacy of existing drugs, such as carvedilol, for rate control and, possibly, suppression of AF, is more appreciated. Efforts are being made to modify existing agents, such as amiodarone, in an attempt to ameliorate safety and adverse effect concerns. This has resulted in promising data from the deiodinated amiodarone analog, dronedarone, and further work with celivarone and ATI-2042. In an attempt to minimize ventricular proarrhythmia, atrial selective drugs, such as intravenous vernakalant, have demonstrated efficacy in terminating AF in addition to promising data in suppression recurrences when used orally. Several other atrial selective drugs are being developed by multiple manufacturers. Other novel therapeutic mechanisms, such as drugs that enhance GAP junction conduction, are being developed to achieve more effective drug therapy than is offered by existing compounds. Finally, nonantiarrhythmic drugs, such as angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, high-mobility group coenzyme A enzyme inhibitors and omega-3 fatty acids/fish oil, appear to have a role in suppressing AF in certain patient subtypes. Future studies will clarify the role of these drugs in treating AF.     

Antioxidant Action of Carvedilol: A Potential Role in Treatment of Heart Failure

Chronic heart failure (CHF) is a progressive disease of diverse origins, multiple mechanisms and complex therapeutic strategies. Contemporary drugs aimed to alleviate the progression of CHF attempt to improve volume/salt loads (edema), correct circulatory aberrations (vascular constriction, low cardiac output) and protect the heart from direct toxic effects of neurohormonal systems such as the renin-angiotensin-aldosterone and the sympathetic nervous system. Most recently (1997) carvedilol (Coreg), a vasodilating beta-adrenergic blocking agent was approved for treatment of heart failure thereby introducing the first beta-blocking agent to heart failure medicine. Carvedilol is a multiple action, non-specific - and ₁-adrenergic receptor blocker and a potent antioxidant agent. Carvedilol has unique antioxidant properties confirmed in physico-chemical, biochemical, cellular and in vivo animal studies. In this paper, the role of oxidative stress in heart failure is reviewed in reference to the antioxidant actions of carvedilol and its possible contribution to the overall efficacy of the drug in reducing morbidity and mortality in heart failure patients.     

Clinical Trials of Carvedilol in Heart Failure

Carvedilol is a non-selective ₁ and -adrenergic antagonist with antioxidant properties. This novel, competitive antagonist has been studied in 8 placebo-controlled clinical trials involving over 1800 heart failure patients with systolic dysfunction in varying degrees of severity. Overall, carvedilol is well-tolerated in heart failure patients, with a predictable reduction in heart rate and favorable hemodynamic actions. The overall incidence of side effects including hypotension, dizziness, bradycardia and worsening heart failure are no worse than placebo, and can be minimized with careful titration. Improvement in left ventricular ejection fraction has been observed with carvedilol in all studies. A significant reduction in the risks of dying or being hospitalized has also been demonstrated. Some studies have demonstrated improvements in clinical parameters such as symptom status and exercise tolerance, but these benefits have been more difficult to demonstrate conclusively. These clinical trials have established an important role of carvedilol in the management of heart failure. The results from the recent survival trials of beta-adrenergic antagonists have confirmed the mortality benefit of this class of drug in the management of patients with heart failure.     

An echocardiographic analysis of the long-term effects of carvedilol on left ventricular remodeling, systolic performance, and ventricular filling patterns in dilated cardiomyopathy

BACKGROUND: The long-term clinical benefit of beta blockade is well recognized, but data quantifying long-term effects of beta blockade on remodeling of the left ventricle (LV) is limited. METHODS: This consecutive series evaluates the long-term response of the LV to the addition of carvedilol to conventional therapy for dilated cardiomyopathy. There were 33 patients who had a LV ejection fraction <45%, LV enlargement and symptomatic heart failure. Quantitative Doppler echocardiography was performed at baseline 6, 12, 24, and 36 months after initiation of carvedilol to evaluate LV ejection fraction, LV volume, wall stress, mass, regional function, and diastolic performance. RESULTS: Compared to baseline there was a significant and sustained reduction in end-systolic volume and end-systolic wall stress with a corresponding improvement in LV ejection fraction. The LV mass did not decline but relative wall thickness increased toward normal. An analysis of regional wall motion responses showed an improvement in all areas, particularly the apical, septal, and lateral walls that was significantly more frequent in patients with a nonischemic etiology. Filling patterns of the LV remained abnormal throughout the study but changed with therapy suggesting a decline in filling pressures. These changes were sustained for 3 years. CONCLUSION: (1) The addition of carvedilol to conventional therapy for a dilated cardiomyopathy significantly improves LV ejection fraction and reduces LV end-systolic volume and wall stress for at least 3 years, (2) the response to 6 months of treatment predicts the long-term response, (3) the typical response is partial improvement of the LV, complete return to normal size, and function is uncommon, and (4) abnormalities of LV filling persist in virtually all patients throughout the course of treatment.     

Electrophysiologic Effects of Carvedilol: Is Carvedilol an Antiarrhythmic Agent?

The cardiovascular drug carvedilol is characterized by multiple pharmacological actions, which translate into a wide-spectrum therapeutic potential. Its major molecular targets are membrane adrenoceptors, ion channels, and reactive oxygen species. Carvedilol's favorable hemodynamic effects are due to the fact that the drug competitively blocks beta(1)-, beta(2)-, and alpha(1)- adrenoceptors. Several additional properties have been documented and may be clinically important, including antioxidant, antiproliferative/antiatherogenic, anti-ischemic, and antihypertrophic effects. The antiarrhythmic action of carvedilol may be related to a combination of its beta-blocking effects with its modulating effects on a variety of ion channels and currents. Several studies suggest that the drug may be useful in reducing cardiac death in high-risk patients with prior myocardial infarction and/or heart failure, as well as for primary and secondary prevention of atrial fibrillation. This article will review experimental data available on the electrophysiologic properties of carvedilol, with a focus on their clinical relevance.     

卡维地洛对大鼠缺血再灌注心肌间隙连接结构影响的研究

目的:研究卡维地洛(CVD)对大鼠缺血再灌注损伤心肌间隙连接(GJ)结构的保护作用.方法:将24只大鼠随机分为假手术(SHAM)组、缺血再灌注(IRI)组和CVD组.CVD组以卡维地洛2mg/kg/d灌胃给药7d,SHAM组和IRI组以等量生理盐水灌胃7d.IRI组和CVD组结扎左冠状动脉前降支致大鼠心肌缺血30min后复灌4h,制作成心肌缺血再灌注损伤模型.SHAM组只穿线不结扎.再灌4h末用免疫荧光和共聚焦显微镜扫描技术观察3组心肌GJ蛋白43(CX43)的分布及组成变化.结果:与SHAM组相比,IRI组CX43-GJ结构明显异常;与IRI组比较,CVD组CX43-GJ结构基本正常.结论:卡维地洛具有保护心肌间隙连接结构的作用.