Essay on the Treatment of Heart Failure | Diseases | Pharmacology

In this essay we will discuss about the drugs used for the treatment of heart failure. 

1. Essay on Diuretics:

The diuretic drugs play a pivotal role in the treatment of heart failure since they are the only drugs that can adequately control the fluid retention; provide symptomatic relief more rapidly than any other drug; and modulate the responses to other drugs because the effects of neurohormonal antagonists (ACE inhibitors and β blockers) are highly dependent on sodium balance.

Diuretics are generally given initially in low doses, which is gradually increased until signs and symptoms of fluid retention are alleviated. NSAIDs should not be given because they decrease the efficacy and increase the toxicity of diuretic therapy.

Thiazide diuretics (hyrochlorothiazide) can be used as initial agents in patients with normal renal functions in whom only a mild diuresis is desired. Loop diuretics (furosemide) should be used in patients who require significant diuresis and in those with markedly decreased renal function. Furosemide reduces preload acutely by causing direct venodilation when administered IV, making it a very useful drug for managing severe HF or acute pulmonary edema. Ethacrynic acid can be used in sulfa-sensitive patents, since furosemide is a sulfa derivative.

The principal adverse effects of diuretic are electrolyte depletion, neurohormonal activation, hypotension and azotemia. Depletion of K⁺ and Mg⁺ can predispose patients to cardiac arrhythmias, particularly in presence of digitalis therapy. Con­comitant treatment with ACE inhibitors, β blockers or aldosterone antagonist prevents the loss of electrolytes caused by diuretics.

ACE inhibitors or β blockers should always be combined with diuretics to counteract any activation of endogenous neuro­hormonal system that may be caused by diuretics. Hypotension and azotemia are generally asymptomatic and require no specific treatment.

2. Essay on ACE Inhibitors:

ACE inhibitors attenuate vasoconstriction, vital organ hypoper­fusion, hyponatremia, hypokalemia and fluid retention attributable to compensatory activation of renin-angiotensin system. The major advantage of ACE inhibitors over traditional (digitalis) treatment is their ability to inhibit the deleterious effects of the neurohormone on the myocardium and the peripheral vasculature.

The beneficial actions of ACE inhibitors are not only due to the interference with the formation of angiotensin II, but are also due to enhancement of the actions of kinins; kinin potentiation may add importantly to angiotensin suppression in mediating the effects of ACE inhibitors.

The favorable effects of ACE inhibitors on the cardiac musculature are greater than those of angiotensin II receptor antagonists. The hemodynamic and prognostic benefits of ACE inhibitors may be attenuated by the co-administration of aspirin, which blocks kinin mediated prostaglandin synthesis.

ACE inhibitors decrease after-load, increase cardiac output and reduce the risk of death or hospitalization in patients with HF. ACE inhibitors have also been shown to reduce the mortality rate in patients with left ventricular systolic dysfunction or HF after an acute attack of myocardial infarction.

ACE inhibitors should not be used before (or instead of) diuretics in patients with a history of fluid retention, because diuretics are needed to maintain Na⁺ balance and to prevent the development of peripheral and pulmonary edema.

ACE inhibitors reduce the need for large doses of diuretics and K⁺ supplement and even attenuate many of the metabolic effects of diuretic therapy (e.g. hypokalemia and hyponatremia). All the available ACE inhibitors can be used. The treatment should be started with low doses followed by gradual increment in dose. Example of starting dosage for ACE inhibitors include captopril 6.25 mg three times a day or lisinopril 2.5-5.0 mg once daily with a target dose of captopril 50 mg three times a day and lisinopril 20 to 35 mg once daily.

The adverse effects of ACE inhibitors are mainly due to the effects of kinin potentiation, which include angioneurotic oedema and cough and their occurrence requires withdrawal of the drug and the use of alternate drugs, i.e. angiotensin II receptor antagonists.

3. Essay on β Blockers:

The use of p blockers in HF was earlier avoided in the treatment of HF. Large clinical trials have shown the beneficial actions of β blockers which are now considered to be an important component of heart failure pharmacotherapy that block the cardiac effects of chronic adrenergic (endogenous neurohormonal system) stimulation, including myocyte toxicity. β blockers should be added to diuretic and ACE inhibitor therapy for patients with stable heart failure symptoms.

β blockers appear to reduce both the risk of death and risk of hospitalisation for heart failure by 30% to 40% in patients already receiving ACE inhibitors, β blockers have been found to be highly effective particularly in reducing cardiac arrhythmias and sudden deaths in the first few weeks after diagnosis of HF.

The hemodynamic benefits of β blockers in HF include; an increase in ejection fraction, reduction in end-systolic volume, improvement in ventricular inco-ordination, improved ventricular filling time, and delaying the process of damage to cardiac muscle.

Individual β blockers have unique properties, and the beneficial effects of β blockers may not be a class effect. Therefore, β blockers with proven effects on patient survival in large clinical trials (bisoprolol, metoprolol, and carvedilol) should be used.

Carvedilol seems to be significantly more efficacious than others in reducing mortality, presumably, because it provides more comprehensive sympathetic antagonism. β blockers should be given in low doses and titrated with careful attention to BP and heart rate.

β blockers are not used in acutely severe HF or patients receiving digitalis or patients with advanced heart block or bronchospastic disease.

4. Essay on Aldosterone Antagonists:

Spironolactone, a potassium sparing diuretic, acts by antagonising an endogenous neurohormonal mechanism that may adversely affect the heart independent of its effects on Na⁺ balance. Low doses of spironolactone have been shown to reduce the risk of death by 25% to 30% due to HF in patients receiving ACE inhibitors.

5. Essay on Digitalis:

Digoxin has little beneficial effect in preventing the progression of HF and there seems to be no justification for its use in early cases of HF, especially when the patient is asymptomatic. Digoxin can be prescribed at any time, if symptoms persist after the use of diuretics and inhibitors of endogenous neurohormonal agents.

Its main use in heart failure is to slow the pulse rate, particularly in atrial fibrillation. Digoxin is not recommended for use in patients who have no symptoms or for the stabilization of patients with acutely decompensated heart failure.