Heart failure

Drug treatment
Drug treatment of heart failure associated with a reduced left ventricular ejection fraction (left
ventricular systolic dysfunction) is covered below; optimal management of heart failure with a
preserved left ventricular ejection fraction has not been established.

The treatment of chronic heart failure aims to relieve symptoms, improve exercise tolerance, reduce the
incidence of acute exacerbations, and reduce mortality. An ACE inhibitor, titrated to a ‘target dose’ (or
the maximum tolerated dose if lower), together with a beta-blocker, form the basis of treatment for all
patients with heart failure due to left ventricular systolic dysfunction.

An ACE inhibitor is generally advised for patients with asymptomatic left ventricular systolic dysfunction
or symptomatic heart failure. An angiotensin-II receptor antagonist may be a useful alternative for
patients who, because of side-effects such as cough, cannot tolerate ACE inhibitors; a relatively high
dose of the angiotensin-II receptor antagonist may be required to produce benefit.

Candesartan cilexetil or valsartan may be given under specialist supervision as adjuncts to an ACE
inhibitor in the treatment of heart failure when other treatments are unsuitable; the concomitant use of
this combination, together with an aldosterone antagonist or a potassium sparing diuretic is not
recommended. The combination of valsartan with sacubitril, an angiotensin-II receptor antagonist with
a neprilysin inhibitor, may be a suitable alternative for those patients already stabilised on an ACE
inhibitor or angiotensin-II receptor antagonist. The beta-blockers bisoprolol fumarate and carvedilol
are of value in any grade of stable heart failure due to left ventricular systolic dysfunction; nebivolol is
licensed for stable mild to moderate heart failure in patients over 70 years. Beta-blocker treatment
should be started by those experienced in the management of heart failure, at a very low dose and
titrated very slowly over a period of weeks or months. Symptoms may deteriorate initially, calling for
adjustment of concomitant therapy.

The aldosterone antagonist spironolactone can be added to an ACE inhibitor and a beta-blocker in
patients who continue to remain symptomatic (particularly in those with moderate to severe heart
failure); low doses of spironolactone reduce symptoms and mortality in these patients. If
spironolactone cannot be used, eplerenone may be considered for the management of heart failure
after an acute myocardial infarction with evidence of left ventricular systolic dysfunction, or for chronic
mild heart failure with left ventricular systolic dysfunction. Close monitoring of serum creatinine, eGFR,
and potassium is necessary, particularly following any change in treatment or any change in the
patient’s clinical condition.

Patients who cannot tolerate an ACE inhibitor or an angiotensin-II receptor antagonist, or in whom
they are contra-indicated, may be given isosorbide dinitrate with hydralazine hydrochloride but this
combination may be poorly tolerated. The combination of isosorbide dinitrate and hydralazine
hydrochloride may be considered in addition to standard therapy with an ACE inhibitor and a beta-
blocker in patients who continue to remain symptomatic (particularly in patients of African or Caribbean
origin who have moderate to severe heart failure).

Digoxin improves symptoms of heart failure and exercise tolerance and reduces hospitalisation due to
acute exacerbations but it does not reduce mortality. Digoxin is reserved for patients with worsening or
severe heart failure due to left ventricular systolic dysfunction who remain symptomatic despite
treatment with an ACE inhibitor and a beta-blocker in combination with either an aldosterone
antagonist, candesartan cilexetil, or isosorbide dinitrate with hydralazine hydrochloride. Patients with
fluid overload should also receive either a loop or a thiazide diuretic (with salt or fluid restriction where
appropriate). A thiazide diuretic may be of benefit in patients with mild heart failure and good renal
function; however, thiazide diuretics are ineffective in patients with poor renal function (eGFR less than
30 mL/minute/1.73 m2) and a loop diuretic is preferred. If diuresis with a single diuretic is insufficient, a
combination of a loop diuretic and a thiazide diuretic may be tried; addition of metolazone may also be
considered but the resulting diuresis may be profound and care is needed to avoid potentially
dangerous electrolyte disturbances.