Drug therapies in chronic heart failure: a focus on reduced ejection fraction

Abstract

There are multiple evidence-based drug treatments for chronic heart failure (HF), both disease-modifying agents and those for symptom control. The majority of the evidence base supports drugs used in HF with reduced left ventricular ejection fraction. The mainstay of disease modification involves manipulation of neurohormonal activation that occurs in HF. In addition to established angiotensin-converting enzyme inhibitors, beta blockers and mineralocorticoid receptor antagonists (MRAs), newer agents are now available such as the angiotensin receptor neprilysin inhibitors. Achieving the optimal drug regimen is complex and best performed by a specialist heart failure team. We aim to provide a comprehensive overview of contemporary drug therapies in chronic heart failure, as well as practical guidance for their use. There is a focus on treating patients with challenging comorbidities such as hypotension and chronic kidney disease (CKD), where a thorough understanding of drug therapy is essential. Multiple trials assessing the benefits of new therapies in HF, such as intravenous iron, are also ongoing.

Fig 1.

Therapeutic algorithm for a patient with symptomatic heart failure with reduced ejection fraction. Reproduced with permission. Green indicates a class I recommendation; yellow indicates a class IIa recommendation. ACEi = angiotensinconverting enzyme inhibitor; ARB = angiotensin receptor blocker; ARNI = angiotensin receptor neprilysin inhibitor; BNP = B-type natriuretic peptide; CRT = cardiac resynchronisation therapy; HF = heart failure; HFrEF = heart failure with reduced ejection fraction; H-ISDN = hydralazine and isosorbide dinitrate; HR = heart rate; ICD = implantable cardioverter defibrillator; LBBB = left bundle branch block; LVAD = left ventricular assist device; LVEF = left ventricular ejection fraction; MR = mineralocorticoid receptor; NTproBNP = N-terminal pro-B type natriuretic peptide; NYHA = New York Heart Association; OMT = optimal medical therapy; VF = ventricular fibrillation; VT = ventricular tachycardia. ^aSymptomatic = NYHA Class II-IV. ^bHFrEF = LVEF <40%. ^cIf ACE inhibitor not tolerated/contraindicated, use ARB. ^dIf MR antagonist not tolerated/contraindicated, use ARB. ^eWith a hospital admission for HF within the last 6 months or with elevated natriuretic peptides (BNP >250 pg/mL or NTproBNP > 500 pg/mL in men and 750 pg/mL in women). ^fWith an elevated plasma natriuretic peptide level (BNP ≥150 pg/mL or plasma NT-proBNP ≥600 pg/mL, or if HF hospitalisation within recent 12 months plasma BNP ≥100 pg/mL or plasma NT-proBNP ≥400 pg/mL). ^gIn doses equivalent to enalapril 10 mg twice a day. ^hWith a hospital admission for HF within the previous year. ⁱCRT is recommended if QRS ≥130 ms and LBBB (in sinus rhythm). ^jCRT should/may be considered if QRS ≥130 ms with non-LBBB (in a sinus rhythm) or for patients in AF provided a strategy to ensure bi-ventricular capture in place (individualised decision).