Chronic Heart Failure Research Paper

The Role of Beta-Blockers in the Treatment of Chronic Heart Failure

In 1988 Sir James Whyte Black was honored with a Nobel Prize for medicine for his efforts in the discovery of the beta blocker propanolol and the histamine receptor agonist cimetidine. Beta blockers were originally developed to treat angina pectoris but were discovered to also treat hypertension, tachycardia, an myocardial infarctions. The discovery of propanolol was said to be the greatest discovery since digitalis.
The mechanism of beta blockers treating CHF is not exact but may include a “reduction in circulating levels of vasoconstrictors, reductions in blood pressure, heart rate and myocardial oxygen consumption, up regulation of myocardial B-1- receptor density, thereby improving contractile function, a reduction in myocardial gene production of inflammatory cytokines, and increase in diastolic perfusion, and normalization of the expression of several myocardial genes involved in the development of pathologic hypertrophy”. The role of beta blockers has changed throughout the decades in part due to the changing theory of heart failure. Heart failure was thought to be
a sole state of decline in systolic function and later updated to reflect it as a complex disorder which consisted of a decrease in cardiac output and compensatory neurohormonal mechanisms. Chronic neurohormonal activation allows for an increase in heart rate and cardiac output, which increases myocardial oxygen demand, ischemia and oxidative stress. In 1975, Waagstein conducted a clinical study testing the role of beta blockers on chf patients. The patients had clinical CHF and tachycardia at rest. Their normal treatment which included a diuretic and digitalis was not altered. The patients were given either alprenolol or practolol for two to twelve months. The results indicated favorable effects as hemodynamics improved, an increase in physical working capacity, and a reduction in heart size. Several more clinical trials were soon to follow.
Eleven studies were disclosed. In 1993, metropolis vs. a placebo in patient with an ejection fraction less than 40% showed that in 383 patients, 34% had a reduction of cardiomyopathy or progression to a heart transplant. In 1994, 641 patients were either on bisoprolol or a placebo. All patients had an ef of less than 40%. No significant difference was concluded. In 1996, 1094 patients with an ef below 35% took cervedilol or the placebo. 65% showed a decrease in mortality and 38% reduction in death or hospitalization. 1999 2647 patients on Bisoprolol and a placebo with an ef less than 35% had a 34% decrease in cardiomyopathy. 2000, 3991 patients took metoprolol, orthe placebo with an ef less than 40%, had a 34% decrease in cardiomyopathy as well. 2001, bucindolol showed no significant difference for patients. 2001 Carvedilol vs. a placebo in 1959 patients indicated a 23% decrease in cardiomyopathy. 2002, Carvedilol showed a 35% decrease in cardiomyopathy. 2003, cervedilol vs. metoprolol had a 17% reduction in cardiomyopathy. 2005, the use of Nebivolol indicated a 14% reduction in either hospitalization or cardiomyopathy. Lastly, in 2006, Bisoprolol was not significant.
Beta blockers properties are not all the same pharmacologically. Is there a superior beta blocker? Carvedilol, bisoprolol, metoprolol, and nebivolol are currently approved to treat CHF. Studies have shown that carvedilol is more effective in terms of cardiac remodeling and central hemodynamics and has advantageous effects on insulin sensitivity that might improve endothelial dysfunction and prevent apotosis.
Beta blockers have also been shown to reduce heart rate. High resting heart rate is a risk factor for mortality and cardiovascular events. Levy conducted a study that concluded patients with a resting heart rate greater than 100 beats per minute had an increased risk of cardiovascular death. A high heart rate, even if moderate, is a prognostic indicator in heart failure patients. A target heart rate for CHF patients is not known, but the beta blocker should be used at the highest tolerated dose for CHF patients, regardless of baseline and achieved heart rate.
Because of the studies and results shown for with the use of beta blockers for CHF patients, beta blockers were soon incorporated into the international guidelines as well as the American heart association for the treatment of CHF.
Beta blockers are recommended for all patients that show symptomatic CHF unless there is a contraindication, but should be clinically stable before starting the regimen. Beneficial effects of beta blockers on morbidity and mortality in patients with CHF are proven. Treatment with beta blockers for patients with heart failure with systolic dysfunction is a huge medical accomplishment . High heart rate patients ultimately have a poorer prognosis and a treatment aimed at the reduction of the heart rate below 70 beats per minute. Beta blockers role to treat these patients is more important than
ever.