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.
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.


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.


CONCLUSIONS
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.
Braun
Martin
M
Department of Internal Medicine and Cardiology, Medical Clinic, University of Technology Dresden, Germany. Martin.Braun@mailbox.tu-dresden.de
Edelmann
Frank
F
Knapp
Markus
M
Schön
Steffen
S
Schwencke
Carsten
C
Simonis
Gregor
G
Borst
Mathias
M
Weinbrenner
Christof
C
Strasser
Ruth H
RH
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D002311:Cardiomyopathy, Dilated / Q000188:drug therapy* / Q000503:physiopathology*; D004311:Double-Blind Method; D015736:Felodipine / Q000627:therapeutic use*; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology*; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D008297:Male; D008790:Metoprolol / Q000037:antagonists & inhibitors*; D008875:Middle Aged; D011446:Prospective Studies; D012720:Severity of Illness Index
D000319:Adrenergic beta-Antagonists; D002121:Calcium Channel Blockers; D008790:Metoprolol; D015736:Felodipine