钙通道阻滞剂非洛地平可减弱β受体阻滞剂美托洛尔在严重扩张型心肌病中的正向血流动力学效应——一项进行有创血流动力学评估的前瞻性、随机、双盲及安慰剂对照研究。

The calcium channel blocker felodipine attenuates the positive hemodynamic effects of the beta-blocker metoprolol in severe dilated cardiomyopathy--a prospective, randomized, double-blind and placebo-controlled study with invasive hemodynamic assessment.

作者信息

Braun Martin, Edelmann Frank, Knapp Markus, Schön Steffen, Schwencke Carsten, Simonis Gregor, Borst Mathias, Weinbrenner Christof, Strasser Ruth H

机构信息

Department of Internal Medicine and Cardiology, Medical Clinic, University of Technology Dresden, Germany.

出版信息

Int J Cardiol. 2009 Feb 20;132(2):248-56. doi: 10.1016/j.ijcard.2008.02.022. Epub 2008 Jun 24.

DOI:10.1016/j.ijcard.2008.02.022

PMID:18579230

Abstract

BACKGROUND

In addition to standard therapy with ACE-inhibitors, digitalis and diuretics, beta-adrenergic receptor blockers have become a widely accepted strategy in the treatment of chronic heart failure. The role of calcium antagonists in CHF however remains controversial. To evaluate if a combination therapy of metoprolol and felodipine might improve hemodynamic parameters, a randomized and placebo-controlled study was designed.

METHODS AND RESULTS

Sixty-three patients with DCMP, LVEF <or=40% being stable for >3 months in NYHA II-III on standard medication were prospectively treated with either a) a combination of metoprolol+felodipine (MF group, n=20), b) metoprolol+felodipine-placebo (MP group, n=23), or c) metoprolol-placebo+felodipine-placebo (PP group, n=20). Compared to baseline, LVEF and LVEDD significantly improved after 6 months in the MP group (LVEF: 36+/-2% vs 29+/-2%, p<0.01; LVEDD: 68+/-3 mm vs 64+/-3 mm, p<0.05), whereas in the other treatment groups only minor changes were observed. A significant benefit in hemodynamic parameters as determined by right heart catheterization was noted also only in the MP group with a marked reduction in PAP mean (17 vs 24 mmHg, p<0.01), PCWP (10 vs 15 mmHg, p<0.001) resulting in a significant increase in cardiac and stroke volume index at rest with no marked changes in the MF and PP group.

CONCLUSION

beta-blocker treatment in CHF patients improves left ventricular function and additionally invasive hemodynamic measurements both at rest and during exercise. In contrast, the combined therapy with the long-acting calcium antagonist felodipine neutralizes these beneficial effects of metoprolol therapy to almost placebo level, providing evidence based on hemodynamic measurements that this combination should be avoided in patients with CHF.

摘要

背景

除了使用血管紧张素转换酶抑制剂、洋地黄和利尿剂进行标准治疗外，β-肾上腺素能受体阻滞剂已成为治疗慢性心力衰竭的一种广泛接受的策略。然而，钙拮抗剂在慢性心力衰竭中的作用仍存在争议。为了评估美托洛尔和非洛地平联合治疗是否能改善血流动力学参数，设计了一项随机、安慰剂对照研究。

方法与结果

63例扩张型心肌病患者，左室射血分数（LVEF）≤40%，在纽约心脏病协会（NYHA）II-III级标准药物治疗下病情稳定超过3个月，前瞻性地接受以下治疗：a）美托洛尔+非洛地平联合治疗（MF组，n = 20）；b）美托洛尔+非洛地平安慰剂治疗（MP组，n = 23）；或c）美托洛尔安慰剂+非洛地平安慰剂治疗（PP组，n = 20）。与基线相比，MP组6个月后LVEF和左室舒张末期内径（LVEDD）显著改善（LVEF：36±2%对29±2%，p<0.01；LVEDD：68±3mm对64±3mm，p<0.05），而其他治疗组仅观察到轻微变化。右心导管检查确定的血流动力学参数的显著益处也仅在MP组中观察到，平均肺动脉压（PAP）显著降低（17对24mmHg，p<0.01），肺毛细血管楔压（PCWP）降低（10对15mmHg，p<0.001），导致静息时心输出量和每搏输出量指数显著增加，而MF组和PP组无明显变化。