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A patient with heart faliure was given Carvedilol. Is there a special pharmacological basis on doing so/
The original thinking was that beta blockers were bad for you is you were in heart failure as they reduce heart rate and myocardial contractility. However when ACE inhibitors were introduced we realised that heart failure brings with it major activation of the sympathetic nervous system and this in turn activates the renin-angiotensin system which then activates the sympathetic nervous system and leading to a vicious cycle of salt and water retention and worsening cardiac perfornance - heart failure begetting heart failure if you like. Beta blockers (particularly when used with ace-inhibitors ) block this cycle. They also probably have a rhythm stabilising effect. There are 4 beta blocker drugs used to treat heart failure carvedilol, metoprolol, bisoprolol and nebivolol. Metoprolol has fallen out of favour (you might like to look at the COMET trial). Carvedilol is a nonselective beta blocker that also vasodilates peripherally potentially reducing some beta blocker side effects. To my knowledge there is very little good data telling us which beta blocker to use in heart failure. I'm not sure if anyone esle knows of any?
Mechanism of Action of BBs in heart failure:
Damage to myocardium after immediate (AMI) or slow onset is not limited; rather resulting in functional decompensation which always leads to widening myocardial damage.This ongoing damage is known as cardiac remodelling. Concentric hypertrophy is due to pressure overload while eccentrici hypertrophy is due to volume overload.
Myocyte, fibroblasts, collagen, the interstitium and the coronary vessels to a lesser extent play a role. Oxidative stress starts a chain of reactions.
Production of Oxygen radicals and hydroxy radicals is increased. Ccavenging enzymes and anti-oxidants and catalases try to overcome this onslaught. When this overwhelmed, mitochondral damage produces further oxidative stress. These processes lead to following 3 major pathways to damamge.
1- Myocyte hypertrophy
As Sadian has mentioned BBs act through neurohormonal mediators to influence this process positively and try to reverse this harmful cardiac remodelling.
These effects are at damaged or prone to damage cell levels. These act through specific receptors in the cell walls. These effects are indedpendent of BP lowering properties.
Aldosterone inhibitors (spirinolactone)
are known benefactors.
New inotropic drugs, New receptor or signal blockers, Nitric oxide donars, metalloproteinases ad Apoptotic inhibitors are being developed.
Found the following studies comparing different beta blockers –
Effects of nebivolol versus carvedilol on left ventricular function in patients with chronic heart failure and reduced left ventricular systolic function.
Randomized trial, found no difference between nebivolol and carvedilol. *
Comparison of effectiveness of carvedilol versus bisoprolol for prevention of postdischarge atrial fibrillation after coronary artery bypass grafting in patients with heart failure
Randomized trial, bisoprolol significantly decreased the risk of AF than carvedilol.**
Effect of selective and non-selective beta-blockers on body weight, insulin resistance and leptin concentration in chronic heart failure.
Randomized trial, carvedilol significantly decreased plasma insulin concentration and insulin resistance compared to bisoprolol. But the sample size is very small.
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