Metra M, Nodari S, Garbellini M, Boldi E, Rosselli F, Milan E, Giubbini R, Dei Cas L
Cattedra di Cardiologia, Università degli Studi, Brescia.
Cardiologia. 1997 May;42(5):503-12.
Carvedilol has been shown to determine a significant improvement in left ventricular function, symptoms, clinical course and prognosis of patients with chronic heart failure. However, these results were obtained in medium-term studies of < 1 year duration. We report the results obtained with long-term (3-4 years) carvedilol administration to 40 patients with idiopathic dilated cardiomyopathy who were initially recruited in a 4-month double-blind placebo-controlled trial. In the initial 4-month double-blind trial, 20 patients were randomized to placebo and 20 to carvedilol treatment. All patients, except one who was not on ACE-inhibitors, were on digoxin, furosemide and ACE-inhibitors. Carvedilol or placebo doses were progressively titrated, at weekly intervals, up to the maximal doses of 25 mg bid. After the initial 4-month double-blind phase, all patients were followed long term. Mean follow-up duration was 52 +/- 12 months (range 48-61). Among the 20 patients initially randomized to carvedilol administration, 4 died (3 for cardiac and 1 for extracardiac causes) and 2 underwent heart transplant. Among the 20 patients initially randomized to placebo, 5 died for cardiac causes, 3 underwent heart transplant and 4 were started on carvedilol because of progressive heart failure during the initial 4 months of the study. The remaining 8 patients, who were kept on digoxin, furosemide and ACE-inhibitors, were used as control group. Each patient underwent an assessment of clinical conditions (NYHA functional classification and Minnesota Living with Heart Failure questionnaire), equilibrium radionuclide ventriculography, and maximal cardiopulmonary bicycle exercise testing. Exams were performed before treatment, after 4 and 12 months, and at the end of the follow-up period. No significant difference between the carvedilol and control group was present at baseline. Compared with baseline, patients in the control group presented a significant increase in left ventricular end-diastolic volume after long-term follow-up (from 126 +/- 62 to 138 +/- 43 and 158 +/- 52 ml/m2 after 12 and 48 months, respectively). No significant difference, compared to baseline values, was noted. Patients on carvedilol presented a persistent improvement in left ventricular function. This was shown by the progressive increment in left ventricular ejection fraction from 22 +/- 6 to 34 +/- 11, 37 +/- 11 and 37 +/- 13%, after 4, 12 and 48 months, respectively (p < 0.001) with a concomitant reduction in left ventricular end-diastolic volume from 147 +/- 54 to 101 +/- 44 ml/m2 at the end of the follow-up (p < 0.05). NYHA functional class remained significantly improved, in comparison with baseline (2.6 +/- 0.5 to 1.9 +/- 0.3, 1.9 +/- 0.8 and 2.0 +/- 1.0 after 4, 12 and 48 months, respectively; p < 0.01). Maximal functional capacity, assessed as peak VO2 was not significantly changed after 4 months (from 15.2 +/- 3.6 to 16.4 +/- 4.0 ml/kg/min) and showed a tendency towards a further improvement after 12 months and at the end of the follow-up (17.3 +/- 5.6 and 17.2 +/- 5.3 ml/kg/min, respectively). These results show that the favorable effects of carvedilol administration on left ventricular function and clinical symptoms are maintained also after long-term treatment.
已证明卡维地洛可显著改善慢性心力衰竭患者的左心室功能、症状、临床病程及预后。然而，这些结果是在为期不到1年的中期研究中获得的。我们报告了对40例特发性扩张型心肌病患者进行长期（3 - 4年）卡维地洛给药的结果，这些患者最初是在一项为期4个月的双盲安慰剂对照试验中招募的。在最初的4个月双盲试验中，20例患者被随机分配至安慰剂组，20例被分配至卡维地洛治疗组。除1例未服用ACE抑制剂的患者外，所有患者均服用地高辛、呋塞米和ACE抑制剂。卡维地洛或安慰剂剂量每周逐步滴定，直至最大剂量25 mg，每日两次。在最初4个月的双盲阶段后，所有患者均进行长期随访。平均随访时间为52±12个月（范围48 - 61个月）。在最初随机分配接受卡维地洛治疗的20例患者中，4例死亡（3例因心脏原因，1例因心脏外原因），2例接受心脏移植。在最初随机分配至安慰剂组的20例患者中，5例因心脏原因死亡，3例接受心脏移植，4例因在研究最初4个月期间出现进行性心力衰竭而开始服用卡维地洛。其余8例继续服用地高辛、呋塞米和ACE抑制剂的患者作为对照组。每位患者均接受临床状况评估（纽约心脏协会功能分级和明尼苏达心力衰竭生活问卷）、平衡放射性核素心室造影及最大心肺运动试验。检查在治疗前、4个月和12个月后以及随访期末进行。卡维地洛组与对照组在基线时无显著差异。与基线相比对照组患者在长期随访后左心室舒张末期容积显著增加（分别在12个月和48个月后从126±62增加至138±43和158±52 ml/m²）。与基线值相比，未观察到显著差异。服用卡维地洛的患者左心室功能持续改善。这表现为左心室射血分数在4个月、12个月和48个月后分别从22±6逐步增加至34±11、37±11和37±13%（p < 0.001），同时随访期末左心室舒张末期容积从147±54减少至101±44 ml/m²（p < 0.05）。与基线相比，纽约心脏协会功能分级仍显著改善（分别在4个月、12个月和48个月后从2.6±0.5改善至1.9±0.3、1.9±0.8和2.0±1.0；p < 0.01）。以峰值VO₂评估的最大功能能力在4个月后无显著变化（从15.2±3.6至16.4±4.0 ml/kg/min），在12个月及随访期末有进一步改善的趋势（分别为17.3±5.6和17.2±5.3 ml/kg/min）。这些结果表明，长期治疗后卡维地洛给药对左心室功能和临床症状的有益作用依然存在。
