Metoprolol succinate for ischemic Heart failure and Carvedilol for non ischemic heart failure

The COMET (Carvedilol or Metoprolol European Trial) showed better outcomes with Carvedilol compared with Metoprolol tarterate in patients with ischemic as well as non-ischemic HF, but from study published in Journal of Cardiac Failure Vol. 18 No. 12 2012, it appears that Metoprolol succinate long acting preparation is superior to Carvedilol for treating ischemic heart failure and Carvedilol is superior to Metoprolol succinate for treating non ischemic heart failure.
The deference in efficacy of Metoprolol for ischemic and Carvedilol for non ischemic heart failure appears to come Patho-physiology of heart failure in these conditions, Beta -1 receptor density is higher in patients of ischemic heart failure as compared to non-ischemic heart failure, so Metoprolol succinate a selective Beta-1 receptor blocker has a edge in treating heart failure due to ischemia.
Infracted myocardium is denervated so nor-epinephrine released is less as compared to non-ischemic myocardium; Carvedilol a non selective blocker; beta-1, beta-2 and alpha blocker reduces myocardial non-epinephrine levels, has an edge in treating non-ischemic heart failure.
In COMET trial Metoprolol tarterate was used, which is a short acting drug, with higher peaks and lower troughs, the higher peak concentrations lead to surges of maximal beta-receptor blockade and loss of selectivity, and the lower troughs lead to loss of beta-1 blockade and potential rebound. These fluctuvations may be reason of lesser efficacy of Metoprolol in ischemic heart failure in COMET study.

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