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Title: A comparison of the mechanisms of action of carvedilol and metoprolol in chronic heart failure
Author: McClure, Samuel J.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2008
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An open label, parallel group study was designed to comprehensively compare and contrast the actions of carvedilol (17 patients) and metoprolol (12 patients) in NYHA class II and III chronic heart failure. Resting heart rate reduction after 20 weeks of treatment with metoprolol (mean reduction of 8.64 beats per minute) was greater than with carvedilol treatment (mean reduction of 4.25 beats per minute). Metoprolol also reduced the heart rate response to dobutamine (p=0.009) and salbutamol (p=0.007) after 20 weeks of treatment, compared to baseline, an effect not seen with carvedilol. Metoprolol reduced plasma renin concentration. Neither beta-blocker affected plasma angiotensin II concentration. Carvedilol significantly decreased plasma aldosterone concentration, and increased plasma atrial natriuretic peptide concentration, after both 10 weeks and 20 weeks. Both drugs increased plasma B-type natriuretic peptide concentrations. Neither agent significantly affected plasma endothelin concentration. Carvedilol alone significantly increased plasma norepinephrine concentration at both time points (+30.9%, p=0.026 and +30.7%, p=0.046). Forearm blood flow (FBF) response to local high dose dobutamine infusion was not reduced by either agent. When FBF was enhanced by local high-dose salbutamol, 20 weeks treatment with metoprolol alone significantly reduced vasodilatation (p=0.028). Neither agent affected the reduction in FBF in response to local high dose phenylephrine nor altered the increase with local high dose acetylcholine. QT dispersion parameters and signal averaged ECG late potentials did not alter significantly with either agent. There was a general non-significant trend for carvedilol to increase LDL oxidation lag time, total plasma antioxidant activity and vitamin E concentration. Metoprolol had the opposite effect on these parameters, vitamin E concentration reduction reaching significance after 20 weeks of treatment (p=0.007). After 20 weeks of treatment, carvedilol (increasing) and metoprolol (decreasing) had divergent but non-significant effects on lymphocyte beta-receptor density. No significant effect of either agent on plasma concentrations of the cytokines TNF-α and sTNFR-1 was detected in this study. These interesting differences between the agents may translate into important clinical effects.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available