Additional Benefits Versus Practicalities of Beta-Blocker Use in CHF Patients: The 'Some Is Better Than None' Rule

Graham Archard

Disclosures

Br J Cardiol. 2005;12(4):313-317. 

In This Article

History of CHF Treatments

Pharmacological treatments for chronic heart failure have been discovered through a variety of Methods, ranging from anecdotal observations made hundreds of years ago to the rational drug design of the 20th century.

The first therapeutic agent to be discovered was digitalis, a positive inotropic agent that allays the symptoms of heart failure. The drug had been used since the 1200s, in the form of a herbal remedy containing the purple foxglove, before the active ingredient was identified by William Withering, who published his findings in 1785. In 1930, the active glycosides present in the fox-glove leaves were isolated and the synthetic agent digoxin was developed as a treatment for chronic heart failure. Today, although randomised controlled trials show that digoxin does not improve overall life expectancy, there is evidence showing a reduction in hospitalization and the drug still plays an important role in the treatment of patients with atrial fibrillation.[1,2]

In contrast to this traditional method of discovery, the original angiotensin-converting enzyme (ACE) inhibitor, captopril, was the first agent to be created through the use of rational drug design (albeit for hypertension rather than heart disease) in the 1970s. ACE inhibitors were soon found to be beneficial in the treatment of chronic heart failure, not only by lowering the blood pressure associated with the disease, but by mechanisms which serve to reverse heart damage. The Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS) and Study of Left Ventricular Dysfunction (SOLVD) studies that investigated mortality risks in patients receiving the ACE inhibitor enalapril found that patients receiving the drug had improvements in New York Heart Association (NYHA) class and a reduction in heart size. This was associated with a significant reduction in mortality.[3,4] As a result, ACE inhibitors are now the first-line therapy recommended for the treatment of chronic heart failure.

The aldosterone antagonist spirono-lactone was originally developed in the 1950s as a potassium-sparing diuretic for the treatment of volume-over-loaded states and primary hyperaldos-teronism. More recently, following recognition of the pathological influence of aldosterone in cardiac disease, and the observation that blockade of angiotensin might be beneficial, the Randomized Aldactone Evaluation Study (RALES) highlighted the value of spironolactone in chronic heart failure. In this study of 1,663 patients, the addition of spironolactone to an ACE inhibitor and a loop diuretic, with or without digoxin, reduced death from progressive heart failure and sudden death from cardiac causes by 30%.[5]

Beta blockers were invented in the 1950s, when the incidence of angina and heart attacks had become a serious health problem in the population. Scientists knew that these problems were caused by a decrease in blood flow to the heart and that incidents of stress could trigger attacks. Thus, it was reasoned that reducing the heart's need for oxygen by controlling the response to stress, i.e. regulating the actions of adrenaline, could prevent these attacks from taking place. Hence, the first beta blocker, propranolol, was invented.[6] Until recently beta blockers were contra-indicated in heart failure because of their negative inotropic effects. It has only lately been realised that the chronic progression of heart damage is caused by the compensatory stimulation of the sympathetic nervous system, which increases the workload of the heart. Beta blockers therefore have longterm benefits and are now recognised as an important adjunct to ACE inhibitors in heart failure treatment.

The most recent drug to be licensed for chronic heart failure is the angiotensin II receptor antagonist, candesartan. A widely used therapy in hypertension, the efficacy of candesartan in the treatment of congestive heart failure was recently established in the Candesartan in Heart Failure Assessment of Reduction in Mortality and Morbidity (CHARM) trial. In this study, candesartan improved NYHA functional class to a similar extent as other established treatments for congestive heart failure across a broad spectrum of patients.[7]

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