Comparison of the effects of carvedilol and metoprolol on exercise ventilatory efficiency in patients with congestive heart failure.

BACKGROUND: The slope of the relationship between ventilation and carbon dioxide production (VE/VCO2 slope), obtained during symptom-limited ramp exercise testing, reflects exercise ventilatory efficiency. Importantly, the VE/VCO2 slope is related to prognosis in patients with congestive heart failure (CHF). The aim of the present study was to determine the relationship between the institution of beta-blockers, carvedilol or metoprolol, and the VE/VCO2 slope during exercise in patients with CHF. METHODS AND RESULTS: Fifty-seven patients with New York Heart Association functional class II or III with a radionuclide left ventricular ejection fraction (LVEF) of less than 40% received carvedilol or metoprolol in a randomized fashion. The VE/VCO2 slope, LVEF and plasma brain natriuretic peptide (BNP) concentration were determined before and after 16 weeks of treatment. LVEF improved (p<0.01), but the VE/VCO2 slope and BNP did not. A significant improvement in the VE/VCO2 slope was observed in patients with LVEF <29% or BNP >63 pg/ml (respective baseline median values) (p<0.05, p<0.05). In patients with BNP >63 pg/ml, the improvement effect on the VE/VCO2 slope with carvedilol was significantly greater than that with metoprolol (p<0.05) and a significant improvement in the VE/VCO2 slope was observed only in those who took carvedilol (p<0.01). CONCLUSIONS: The VE/VCO2 slope was not improved after beta-blocker therapy in any of the patients. However, it did improve in patients with a lower LVEF or higher BNP level at baseline, and carvedilol was more effective than metoprolol in improving the VE/VCO2 slope in patients with higher BNP levels at baseline.     

Effect of beta blockade (carvedilol or metoprolol) on activation of the renin-angiotensin-aldosterone system and natriuretic peptides in chronic heart failure

Beta blockers are known to suppress renin release in hypertension and in patients taking angiotensin-converting enzyme (ACE) inhibitors. This study sought to explore the effect of additional beta blockade on neurohumoral modulation in patients with severe heart failure (HF) who received ACE inhibitors. Forty-nine patients with chronic HF who received ACE inhibitors were given metoprolol 50 mg or carvedilol 25 mg twice daily after a 4-week dose titration period in addition to standard therapy in a prospective trial. Samples of plasma renin activity (PRA), aldosterone, aminoterminal B-type natriuretic peptide (N-BNP), and atrial natriuretic peptide (ANP) were taken at baseline and at 4, 12, and 52 weeks after starting therapy. Treatment with either beta blocker significantly lowered PRA at 4 weeks compared with baseline (-2.0 +/- 0.6 nmol/L/hour, p = 0.006), but at 12 weeks, PRA had reduced to -1.1 +/- 0.6 nmol/L/hour (p = 0.08), but at 52 weeks, it was not significantly different from baseline (+1.05 +/- 0.6 nmol/L/hour, p = 0.13). Aldosterone levels did not change significantly from baseline at 4 or 12 weeks, although there was a nonsignificant trend for lower levels at 52 weeks (baseline 232 +/- 154 pmol/L, 52 weeks 192 +/- 100 pmol/L, p = 0.09). There was significant reduction in N-BNP and ANP together with an improvement in symptom and left ventricular systolic function at 1-year follow-up. These results indicate that the suppressive effect of beta blockers on PRA in patients with HF taking ACE inhibitors is temporary, and that there is no significant effect on serum aldosterone levels.     

卡维地洛治疗充血性心力衰竭的临床研究

目的:探讨卡维地洛对充血性心力衰竭(CHF)患者心功能的影响。方法:45例CHF患者被随机分成2组.对照组(B组)用利尿剂、强心甙、硝酸酯类等药进行治疗,治疗组(A组)在B组治疗基础上加用卡维地洛,起始剂量3.125mg,2次/d,每2周加量1倍,至最大剂量25mg,2次/d。结果:治疗16周后,两组的心功能分级均有明显改善.与对照组比较,治疗组LVEF增加更加显著(P<0.05)。结论:卡维地洛对CHF有较好的疗效。     

Comprehensive adrenergic receptor blockade with carvedilol is superior to beta-1-selective blockade with metoprolol in patients with heart failure: COMET

The Carvedilol or Metoprolol European Trial (COMET) compared the effects of a comprehensive adrenergic antagonist, carvedilol (target dosage 25 mg twice daily), with a β-1-selective agent, metoprolol tartrate (target dosage 50 mg twice daily), in 3029 patients with chronic heart failure caused by left ventricular systolic dysfunction. The study showed that, compared with metoprolol, long-term treatment with carvedilol exerted a substantially greater reduction in mortality and led to improvement in well-being in these patients. The superiority of carvedilol over metoprolol is readily explained by differences in their pharmacologic profiles. There is no evidence, within the trial or from other sources, that the relative dose of each agent or their formulation explained the observed difference. The result of COMET is entirely consistent with the results of previous placebo-controlled trials of β-1-selective blockers and carvedilol.     

美托洛尔对合并糖尿病心衰患者外周血淋巴细胞β受体密度影响的临床研究

目的　比较美托洛尔对合并与未合并 2型糖尿病的心力衰竭 (心衰 )患者心功能及血浆淋巴细胞 β受体密度影响的差异。方法　 6 2例心衰患者予美托洛尔治疗 ,其中 31例合并 2型糖尿病。采用3 H CGP12 177放射配基法 ,测定并计算治疗前后外周血淋巴细胞 β受体最大结合量(Bmax)。同时检测 4 3例正常人外周血淋巴细胞 β受体Bmax。结果　合并 2型糖尿病的心衰患者接受美托洛尔治疗 ,血浆淋巴细胞 β受体密度显著上调 ,与非糖尿病患者相似 (P >0 0 5 )。结论　与非糖尿病患者相比 ,合并 2型糖尿病的心衰患者予以美托洛尔治疗 ,同样获益     

卡维地洛与美托洛尔治疗缺血性心脏病心力衰竭的疗效观察

目的:观察卡维地洛和美托洛尔对缺血性心脏病心力衰竭患者的临床疗效。方法:缺血性心脏病心力衰竭患者80例,左室射血分数（LVEF）≤0.45,心功能（NYHA）ⅡⅣ级,常规治疗基础上随机分为卡维地洛组和美托洛尔组,治疗3月后,观察两种药物对心功能及运动耐量的影响。应用心脏彩色超声仪测定心功能基线值及3月后的变化。用6 m in步行距离测定运动耐量的改善程度。结果:经过3月的治疗,卡维地洛组与美托洛尔组心率、血压、运动耐量改善程度及心功能均有明显改善,且卡维地洛组6 m in步行试验结果,收缩压、舒张压变化及左室收缩末容积（LVESV）、左室舒张末容积（LVEDV）、LVEF改善程度明显优于美托洛尔组（P<0.01）。结论:在常规治疗基础上卡维地洛、美托洛尔对缺血性心脏病的治疗均有显著效果,前者在改善运动耐量、LVEDV、LVESV及心室射血方面更优。     

美托洛尔和卡维地洛对慢性心力衰竭的影响

目的比较选择性β1受体阻滞剂美托洛尔和非选择性β受体阻滞剂卡维地洛治疗对慢性心力衰竭(CHF)代谢底物、细胞因子及心脏功能的影响。方法选择CHF患者86例(CHF组)及健康体检者25例(正常对照组)。CHF组患者又随机分为美托洛尔组(43例)和卡维地洛组(43例)。记录两组CHF患者治疗前后心功能分级及不良事件次数及TNF-α、白细胞介素-1β(IL-1β)和白细胞介素-6(IL-6)含量。所有入选者均测定血清游离脂肪酸(FFA)含量。结果美托洛尔组和卡维地洛组患者经过治疗后心功能明显改善(P<0.01),其中卡维地洛组更加明显(P<0.01)。美托洛尔组不良事件40次,卡维地洛组不良事件24次(P<0.01)。血浆TNF-α、IL-1β和IL-6较治疗前显著降低(P<0.05)。卡维地洛组较美托洛尔组TNFα和IL-1β降低更明显(P<0.01,P<0.05)。CHF组患者血清FFA含量同正常对照组比较明显升高(P<0.01)。治疗后卡维地洛组血清FFA较美托洛尔组降低更明显(P<0.01)。结论β受体阻滞剂可以改善CHF患者心功能,降低血浆细胞因子及FFA水平,非选择性的β受体阻滞剂卡维地洛优于选择性的β1受体阻滞剂美托洛尔。     

卡维地洛治疗扩张型心肌病心力衰竭疗效观察

目的　评价第三代 β受体阻滞剂卡维地洛治疗扩张型心肌病 (DCM)心力衰竭的临床疗效。方法　 6 2例 DCM心力衰竭患者在接受常规治疗 (洋地黄、利尿剂、血管紧张素转换酶抑制剂 )病情稳定后 ,随机分为卡维地洛组和美多心安组。均从小剂量 (卡维地洛组 ,2 .5 m g bid;美多心安组 ,6 .2 5 m g bid)缓慢递增。检测治疗前后 DCM患者左心室功能和结构的变化以及血液中内皮素 - 1(ET- 1)、心钠素 (ANP)和血管紧张素 (Ang )的改变。结果　治疗 6个月后 ,两组心脏功能分级均明显改善 ,左心室射血分数 (L VEF)、短轴缩短率 (FS)、左心室射血前期与射血时间比(PEP/ L VET)、舒张早期峰值血流速度 (PFVE)、舒张早期峰值血流速度与舒张晚期峰值血流速度比 (PFVE/ PF-VA)均明显增加 ,卡维地洛组较美多心安组 L VEF增加更为明显。两组左心房内径 (L AD)、左心室收缩末期内径(L VSD)、左心室舒张末期内径 (L VDD)明显减小 ,卡维地洛组 L VSD减小较美多心安组更明显。治疗后血浆中ET- 1、ANP和 Ang 均明显降低。结论　卡维地洛和美多心安都能够改善 DCM心力衰竭患者左心室收缩和舒张功能 ,逆转左心室重构 ,卡维地洛较美多心安疗效更佳。     

Effects of metoprolol in chagasic patients with severe congestive heart failure

BACKGROUND: Beta-blockers are the most effective and promising treatment for congestive heart failure secondary to left ventricular dysfunction and sympathetic activation. METHODS: Since chagasic patients with severe congestive heart failure have left ventricular systolic dysfunction and neurohormonal activation, we administered metoprolol to nine chagasic patients who were in severe congestive heart failure. Metoprolol (5 mg p.o. daily) was uptitrated on a weekly basis. RESULTS: Patients were receiving digitalis, diuretics and angiotensin converting enzyme inhibitors and had left ventricular dilatation (6.77+/-0.89 cm), depressed ejection fraction (0.20+/-0.06), low systolic blood pressure (93+/-11 mm Hg), sinus tachycardia (115+/-17 beats/min) and sympathetic activation 400+/-246 pg/ml). One patient was in New York Heart Association Functional class III and eight patients were in functional class IV. At the end of the fifth week of treatment (metoprolol 25 mg), seven patients were in functional class III and two were in functional class II. Heart rate decreased to 85+/-15 beats/min (P<0.05) and the systolic blood pressure increased to 108+/-18 mm Hg (P<0.01). There were no significant changes in left ventricular ejection fraction. By the end of the tenth week of treatment (metoprolol 50 mg), four patients were now in functional class I and five were in functional class II. Left ventricular ejection fraction increased to 0.27+/-0.05 (P<0.01) and the left ventricular systolic diameter decreased from 6.38+/-0.90 at baseline to 5.89+/-0.59 and 5.76+/-0.96 after 25 and 50 mg of metoprolol treatment, respectively (P<0.04). Plasma norepinephrine decreased non-significantly to 288+/-91 pg/ml. CONCLUSION: Beta-blockers improve the clinical status and the left ventricular function of chagasic patients with severe congestive heart failure.     

卡维地洛对充血性心力衰竭患者心功能的影响

目的　探讨卡维地洛对充血性心力衰竭患者心功能的影响。　方法　充血性心力衰竭患者 6 2例(其中扩张性心肌病心力衰竭患者 15例 ,缺血性心脏病心力衰竭患者 4 7例 ) ,左室射血分数 (LVEF)≤ 4 0 % ,心功能(NYHA)Ⅱ～Ⅳ级 ,常规治疗 (洋地黄 ,利尿剂 ,ACEI)基础上随机分为卡维地洛试验组和安慰剂对照组。应用心脏彩色超声仪测定治疗前及治疗后 1个月 ,3个月左室结构和功能指标的变化。观察卡维地洛治疗三个月后对心功能的影响。　结果　卡维地洛平均用量为 2 1 1mg d± 9 6mg d。经过 3个月治疗 ,试验组症状和心功能改善 ,与对照组比较左室射血分数上升 (P <0 0 0 2 ) ,左室收缩末容积下降 (P <0 0 5 ) ;左室舒张末容积与对照组比较虽无统计学差异但与治疗前比较亦明显下降 (P <0 0 5 )。　结论　在洋地黄、利尿剂、ACEI的治疗基础上 ,应用卡维地洛能显著改善充血性心力衰竭患者的心功能 ,改善心室结构 ,且疗效与应用剂量无关。     

Effects of carvedilol therapy on arrhythmia markers in patients with congestive heart failure

The aim of this study was investigate the effects of carvedilol therapy on ventricular repolarization characteristics as assessed by QT dispersion (QTd) and heart rate variability (HRV) in patients with heart failure. Thirty-one patients with heart failure (mean age, 63.9 years) were included in the study. Carvedilol was administered in addition to standard therapy for CHF at a dose of 6.25 mg/day and uptitrated to the maximum tolerated dose. Control group consisted of 14 patients with heart failure (mean age, 69.4 years) who could not take carvedilol due to several reasons. All patients were followed-up 6 months. QT dispersion (QTd), and corrected QTd (QTcd) values were calculated at baseline and at the end of follow-up. Time domain and frequency domain heart rate variability analysis were performed with ambulatory Holter ECG. Mean carvedilol dose was 23.9 +/- 13.9 mg. Significant reductions were observed in the QTd (P = 0.016) and QTcd (P = 0.001) with carvedilol therapy, whereas QTd (P = 0.47) and QTcd (P = 0.43) did not change significantly in the control group. The QT maximum value did not change significantly but the QT minimum value (P = 0.03) was significantly increased after carvedilol therapy. Although the mean SDANN value was improved (P = 0.039), other HRV parameters such as mean SDNN (P = 0.32), rMSSD (P = 0.74), and the LF/HF ratio (P = 0.35) did not change significantly after carvedilol therapy. This prospective controlled study shows that carvedilol therapy decreased QT dispersion and improved ventricular repolarization characteristics but did not change autonomic dysfunction in patients with heart failure.     

缬沙坦联合美托洛尔治疗充血性心力衰竭疗效观察

目的探讨缬沙坦联合美托洛尔治疗慢性充血性心力衰竭(congestive heart failure,CHF)的临床疗效。方法70例CHF患者用随机单肓对照法分成A组和B组。A组36例给予强心苷及利尿药常规治疗;B组34例在常规治疗基础上加缬沙坦联合美托洛尔,疗程6个月。结果治疗后,B组临床总有效率为85%,A组总有效率56%,两组差别具有统计学意义(P<0.01);两组治疗前后心率、心胸比率、左心室舒张末期内径、左心室收缩末期内径均明显减小、左心室射血分数相比显著增加(P<0.01),未见明显副作用。结论缬沙坦联合美托洛尔治疗CHF疗效优于强心苷及利尿药常规治疗。     

卡维地洛对心力衰竭病人肾上腺素能受体自身抗体及镁代谢的影响

目的 探讨卡维地洛对慢性心力衰竭病人肾上腺素能受体β1、β2、α1自身抗体及Mg2＋代谢的影响.方法 慢性心功能不全病人60例,分为卡维地洛组36例和常规治疗组24例,正常对照为健康体检者30例.常规治疗组用血管紧张素转化酶抑制药、利尿剂和强心苷.卡维地洛组在常规治疗的基础上加用卡维地洛.随访6个月,用超声心动图测定心功能参数,酶联免疫吸附实验测定血浆β1、β2、α1自身抗体,测外周单核细胞Mg2＋含量及24 h尿Mg2＋排泄量.结果 治疗后,卡维地洛组左心室舒张末内径和收缩末内径分别为（57±6）mm和（43±6）mm,显著低于常规治疗组的（64±4）mm和（52±5）mm,差异有统计学意义（P＜0.01）;左心室射血分数为0.51±0.08,显著高于常规治疗组的0.42±0.06（P＜0.01）.治疗后卡维地洛组3种抗体阳性率及抗体滴度均显著低于治疗前（P＜0.01）,且卡维地洛组3种抗体阳性率及抗体滴度均显著低于常规治疗组,差异有统计学意义（P＜0.01）.心力衰竭病人尿Mg2＋排泄量明显升高（P＜0.01）,单核细胞Mg2＋含量降低（P＜0.01）.结论 β1、β2、α1受体参与心力衰竭的发生和发展过程,卡维地洛通过阻断β1、β2、α1受体改善心功能,同时减少尿镁排泄,增加细胞内镁水平.     

厄贝沙坦联合美托洛尔治疗充血性心力衰竭疗效观察

目的：观察厄贝沙坦联合美托洛尔治疗充血性心力衰竭（CHF）的临床疗效。方法：122例CHF患者被分为观察组（62例）和常规治疗组（60例）,常规治疗组予以常规用药（洋地黄、血管扩张剂、利尿剂等）综合治疗,观察组在常规治疗组基础上联合使用厄贝沙坦和美托洛尔,两组疗程均为12～16周。观察治疗前后心功能、左室射血分数（LVEF）、左室舒张末内径（LVEDd）、左室收缩末内径（LVESd）、心率及血压等指标的变化。结果：观察组总有效率明显高于常规治疗组（93．55％比76．67％,P〈0．05）;与治疗前比较,观察组治疗后LVEDd[（66．92±5．16）mm比（50．52±6．30）mm]、LVESd[（61．80±4．58）mm比（49．86±5．20）mini显著降低（P均〈0．05）,且较常规治疗组治疗后降低更显著[LVEDd（59．70±6．28）mm,LVESd（57．65±4．20）mm,P〈0．05];两组治疗后LVEF均有明显增加（P〈0．05～0．01）,且观察组明显高于常规治疗组[（48．84±4．45）％比（37．58±3．15）％,P〈0．05];观察组收缩压、舒张压、心率均较治疗前明显改善（P〈0．05）,且舒张压[（60．99±12．98）mmHg比（75．97±13．62）mmHg]、心率[（70．99±10．7）次／min比（75．73±9．38）次／min]较常规治疗组明显降低（P均〈0．05）。结论：在常规用药基础上加用厄贝沙坦及美托洛尔治疗充血性心力衰竭患者疗效更显著。