Heart failure with reduced ejection fraction
Chronic heart failure with a left-ventricular ejection fraction of 40 percent or below. Foundational therapy per ESC 2023: ACE inhibitor or ARB (or ARNI), beta-blocker, mineralocorticoid receptor antagonist, and SGLT2 inhibitor.
ICD-10 I50.15 drugs
Also known as: HFrEF, Systolic heart failure
Drugs used for this condition
- ACandesartanFirst line · Angiotensin II receptor blockerCandesartan reduces cardiovascular mortality and hospitalization in heart failure with reduced ejection fraction, as shown in the CHARM program (Lancet 2003): three trials in patients with EF 40 percent or below, including CHARM-Alternative in ACE-inhibitor-intolerant patients. ESC 2023 and NICE NG106 recommend ARBs as an alternative to ACE inhibitors in patients with cough or a history of angioedema.
- ANitroglycerinSecond line · Organic nitrateIn acute decompensated heart failure with pulmonary congestion and preserved arterial perfusion, intravenous nitroglycerin lowers preload, reduces dyspnea, and unloads the left ventricle. ESC 2023 recommends use in patients with systolic BP above 110 mm Hg. Start infusion at 10–20 mcg/min with titration by BP and symptoms. Avoided in cardiogenic shock and systolic BP below 90 mm Hg.
- ASacubitril + ValsartanFirst line · Angiotensin receptor-neprilysin inhibitor (ARNI)Heart failure with reduced ejection fraction (≤40%) in adults. Per ESC HF 2021 and AHA/ACC/HFSA 2022, ARNI is part of foundational quadruple therapy with a beta-blocker, MRA, and SGLT2 inhibitor. ACEi/ARB-naïve patients start at 49/51 mg twice daily; patients switching from enalapril require a 36-hour washout (angioedema risk). Up-titrate to 97/103 mg twice daily over 2–4 weeks with BP and K+ monitoring.
- BCaptoprilAdd-on therapy · ACE inhibitorCaptopril reduces mortality and hospitalization in chronic heart failure with reduced ejection fraction, as shown in the SAVE trial (1992) in post-MI patients with EF 40 percent or below. ESC 2023 and NICE NG106 include ACE inhibitors as a baseline component of quadruple therapy (with a beta-blocker, mineralocorticoid receptor antagonist, and SGLT2 inhibitor). Captopril is rarely used in this role because of 2–3 daily dosing; enalapril, lisinopril, and ramipril are preferred.
Marketing claims without evidence base
The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.
How to read tiers A–F
Evidence tiers belong to the drug-indication pair, not to the drug as a whole: the same substance can be A for one condition and F for another.
- AStrong evidence – first or second line in international guidelines
- BRecommended in selected cases
- CStudy data contradict each other
- DBenefit not proven, no documented harm
- FDocumented harm, or risk without benefit