Pharmacotherapy of Chronic Heart Failure with Reduced EF LV - Latest ESC Recommendations

Basic drug groups in the treatment of HFrEF

In the treatment of chronic heart failure (NYHA class II–IV) with reduced ejection fraction of the left ventricle (EF LV ≤ 40%), it is recommended for all patients to block the renin-angiotensin-aldosterone system either with angiotensin-converting enzyme inhibitors (ACEi) or angiotensin II receptor blockers (ARBs) and neprilysin inhibitors (ARNI), which have shown to reduce mortality and risk of hospitalization for heart failure in these patients. Along with beta-blockers (BB) and mineralocorticoid receptor antagonists (MRA), they form the basis of therapy for patients with heart failure with reduced EF (HFrEF), unless contraindicated. Their dose should be titrated to the level used in clinical studies or the maximum tolerated dose.

Recommendations for administering ARNI

ARNI should be administered instead of ACEi in patients who continue to exhibit heart failure symptoms despite the use of ACEi, BB, or MRA. ARNI can also be considered as first-line therapy instead of ACEi. Initiating treatment with this preparation appears safe, and several studies have shown that sacubitril/valsartan (an ARNI representative) reduces cardiovascular mortality and the need for hospitalization for heart failure in HFrEF by about 40% compared to enalapril. Angiotensin II receptor blockers (ARBs, sartans) have a role in the treatment of HFrEF in patients who do not tolerate ACEi or ARNI.

Recommendations for administering gliflozins

Recent evidence has shown that sodium-glucose cotransporter-2 inhibitors (SGLT2i, gliflozins) developed as antidiabetics reduce cardiovascular mortality and the risk of worsening heart failure in patients with HFrEF regardless of the presence of diabetes when added to ACEi/ARNI, BB, or MRA. Therefore, dapagliflozin or empagliflozin are newly recommended for all patients with HFrEF, unless contraindicated, regardless of whether the patient has diabetes mellitus.

Recommendations for other medications

Other medications that can be considered in the treatment of HFrEF include diuretics, which are recommended for patients with signs or symptoms of congestion, aiming to alleviate symptoms, increase exercise capacity, and reduce the frequency of hospitalizations for heart failure.

The If channel inhibitor ivabradine can be considered for symptomatic patients with EF LV ≤ 35%, sinus rhythm, and resting heart rate > 70/min treated with the maximum tolerated dose of BB (or without this treatment in case of BB intolerance), ACEi/ARNI, and MRA. The goal of adding ivabradine is to reduce the risk of hospitalization and cardiovascular mortality.

For patients with worsening heart failure despite treatment with ACEi/ARNI, BB, or MRA, the addition of a soluble guanylate cyclase stimulator – vericiguat – can be considered to reduce mortality and hospitalizations for heart failure.

The goal of reducing the overall risk of hospitalization can also be met by adding digoxin, which can be considered for patients with sinus rhythm and symptomatic HFrEF even while on treatment with ACEi/ARNI, BB, or MRA.

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Source: McDonagh T. A., Metra M., Adamo M. et al.; ESC Scientific Document Group. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J 2021 Sep 21; 42 (36): 3599−3726, doi: 10.1093/eurheartj/ehab368.