Heart failure
Clinical syndrome resulting from the heart's inability to maintain adequate tissue perfusion. Presents with dyspnea, fluid retention, and reduced exercise tolerance.
ICD-10 I5020 drugs
Also known as: HF, CHF, Heart failure with reduced ejection fraction, HFrEF
Drugs used for this condition
- ABisoprololFirst line · Selective beta-adrenergic blockersBisoprolol is one of three beta-blockers proven to reduce mortality in HFrEF (alongside carvedilol and metoprolol succinate). The CIBIS-II trial showed a 34 % reduction in all-cause mortality. Start at 1.25 mg daily, titrate every 2 weeks to target dose of 10 mg.
- ADapagliflozinFirst line · Sodium-glucose cotransporter-2 (SGLT2) inhibitorFoundation therapy in chronic HF per ESC 2023 as one of four «fundamental» components (ARNI/ACE-I + β-blocker + aldosterone antagonist + SGLT2 inhibitor). DAPA-HF (2019) showed 26% reduction in cardiovascular death or HF hospitalization in HFrEF; DELIVER (2022) – 18% in HFpEF. Effect independent of diabetes. Dose 10 mg once daily.
- AEmpagliflozinFirst line · Sodium-glucose co-transporter 2 inhibitors (SGLT2i)Empagliflozin is one of the four pillars of HFrEF therapy per ESC HF 2021 alongside ACEi/ARNI, beta-blockers, and MRAs. EMPEROR-Reduced (3,730 patients) showed a 25 % reduction in the composite of cardiovascular death or HF hospitalization. EMPEROR-Preserved (5,988 patients) was the first RCT to prove pharmacological benefit in HFpEF: 21 % reduction in the same composite. Diabetes status does not affect the indication.
- AEnalaprilFirst line · Angiotensin-converting enzyme inhibitors (ACEi)ACE inhibitors are one of the four pillars of HFrEF therapy together with beta-blockers, MRAs, and SGLT2 inhibitors. They reduce all-cause mortality and hospitalizations. Start low (2.5 mg BID) and titrate to maximum tolerated dose monitoring blood pressure, renal function, and potassium. ESC HF 2021 now prefers sacubitril/valsartan, but enalapril remains an evidence-based alternative.
- AEplerenoneFirst line · Selective mineralocorticoid receptor antagonistFoundation therapy in heart failure with reduced ejection fraction (HFrEF) per ESC 2023 alongside spironolactone. Cuts mortality and cardiovascular hospitalization by 15% (EMPHASIS-HF, NYHA II). Starting dose 25 mg once daily, uptitrated to 50 mg over 4 weeks. Also indicated post-MI in patients with EF below 40% and HF symptoms or diabetes (EPHESUS).
- AIvabradineSecond line · Selective If channel inhibitor of the sinoatrial nodeSecond-line in HFrEF per ESC 2023 in symptomatic NYHA II–IV patients with sinus rhythm, HR ≥75 bpm, EF ≤35%. Added to standard therapy (ARNI/ACEi, β-blockers, aldosterone antagonists, SGLT2 inhibitors) when β-blockers are contraindicated or HR remains high on maximum tolerated dose. SHIFT showed 18% reduction in cardiovascular death or HF hospitalization. Starting dose 5 mg twice daily, titrated to 7.5 mg twice daily.
- AMetoprololFirst line · Selective β1-adrenoceptor blockersMetoprolol succinate is one of three beta-blockers proven to reduce mortality in HFrEF. The MERIT-HF trial demonstrated a 34% reduction in all-cause mortality. Start at 12.5–25 mg daily, titrate every 2 weeks to target dose of 200 mg. Succinate must not be substituted with tartrate – they are not equivalent in HF. ESC 2021 includes metoprolol succinate among recommended beta-blockers for HF.
- ANebivololFirst line · Highly selective β1-blocker with endothelial nitric oxide releaseIn heart failure in patients over 70, nebivolol cuts the composite of death and cardiovascular hospitalization by 14% (SENIORS). Start at 1.25 mg with weekly–biweekly titration up to the target 10 mg under BP and HR monitoring.
- ARamiprilFirst line · Angiotensin-converting enzyme inhibitor (ACE-I)Foundation therapy in HFrEF per ESC 2023 alongside other ACE inhibitors. AIRE trial showed 27% mortality reduction in post-MI HF. Dose 2.5–10 mg once daily titrated from the minimum.
- ASpironolactoneFirst line · Potassium-sparing diuretics (mineralocorticoid receptor antagonists)Spironolactone 25–50 mg daily is a cornerstone of HFrEF therapy. The RALES trial showed a 30% mortality reduction when spironolactone was added to standard treatment (ACEi + loop diuretic). Prescribed when potassium is below 5.0 mmol/L and eGFR above 30. Monitor potassium and creatinine one week after initiation and with each dose change.
- ATorasemideFirst line · Loop diuretic – sulfonamide derivativeFirst-line for symptomatic congestion in chronic heart failure per ESC 2023 alongside furosemide. Dose 5–20 mg once daily. TORIC and DiNicolantonio 2012 meta-analysis showed 13% mortality reduction and 20% fewer hospitalizations in HF versus furosemide – likely due to additional antialdosterone effect.
- BDigoxinCase-by-case decision · Cardiac glycosides (digitalis)Per ESC HF 2021, digoxin (class IIb, level B) is considered in HFrEF patients in sinus rhythm with persisting symptoms after full four-pillar therapy. Digoxin does not affect overall mortality (DIG trial 1997) but reduces decompensation hospitalisations. Target serum level 0.5–0.9 ng/mL; levels above 1.2 ng/mL increase mortality. In AF with HF, digoxin remains relevant for rate control in sedentary patients and in those with hypotension.
- BIsosorbide mononitrateSecond line · Long-acting organic nitrateUsed with hydralazine in heart failure with reduced ejection fraction in African American patients (A-HeFT) or with ACEi/ARB intolerance. ESC 2023 does not list it as first-line in the general population – base therapy is ARNI (sacubitril-valsartan), β-blockers, aldosterone antagonists, SGLT2 inhibitors.
- BLosartanFirst line · Angiotensin II receptor blockers (sartans)ARBs are an alternative to ACE inhibitors in HFrEF when ACEi are not tolerated due to cough. Mortality and hospitalization reduction is comparable to ACEi based on CHARM-Alternative (candesartan) and ELITE II (losartan) trials. Titration to maximum tolerated dose is mandatory.
- BValsartanSecond line · Angiotensin II receptor blockers (ARBs)Valsartan is a proven ACE inhibitor alternative in HFrEF. The Val-HeFT trial showed a 27% reduction in hospitalizations when valsartan was added to background therapy. Sacubitril/valsartan (Entresto) is a separate drug that outperformed enalapril in PARADIGM-HF and is now preferred in HFrEF.
- CLevocarnitine (L-carnitine)Case-by-case decision · Amino acid derivative; cofactor for long-chain fatty acid transport into mitochondriaL-carnitine has been studied as an adjunct in chronic heart failure for its role in myocardial energetics. The 2023 ESC guidelines do not mention L-carnitine for heart failure treatment: first-line therapy includes RAAS inhibitors, beta-blockers, mineralocorticoid receptor antagonists and SGLT2 inhibitors. Some RCTs report a small ejection-fraction improvement in dilated cardiomyopathy, but sample sizes are small and independent confirmation is lacking. Use is an individual decision, never as a replacement for evidence-based therapy.
- CUbidecarenone (coenzyme Q10)Case-by-case decision · Other cardiac preparations. Coenzyme Q10In chronic heart failure, coenzyme Q10 has been studied as add-on therapy to guideline-directed treatment (ACE inhibitors/ARNI, β-blockers, mineralocorticoid receptor antagonists). The Q-SYMBIO trial (Mortensen 2014, n=420, 2 years) showed 43% reduction in the composite endpoint (mortality + adverse cardiovascular events) at 300 mg/day. The result is criticized for small sample size and design issues. ESC 2021 HF guidelines do not include CoQ10 as mandatory therapy but describe it as an «acceptable add-on option». AHA/ACC 2022 guidelines do not mention CoQ10.
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.
- DD-riboseNot recommended · Pentose monosaccharide; complemento alimenticio with a claimed role in energy metabolismD-ribose is offered as heart failure support by analogy with its theoretical role in myocardial ATP synthesis. The 2023 ESC guidelines do not mention D-ribose: first-line therapy is RAAS inhibitors, beta-blockers, mineralocorticoid receptor antagonists and SGLT2 inhibitors. The small Omran 2003 RCT (15 patients) showed improved diastolic function and quality of life, not reproduced in larger studies. Replacing evidence-based therapy with D-ribose risks decompensation.
- FAzilsartan medoxomilNot recommended · Angiotensin II receptor blockerSartans belong in heart failure regimens with reduced ejection fraction, but not all of them: the evidence sits with candesartan, valsartan and losartan, and European guidelines name those molecules. Azilsartan took part in no heart failure trial, and the AEMPS Edarbi label keeps the indication at essential hypertension. Swapping candesartan for azilsartan inside a heart failure regimen looks like a like-for-like change, yet nothing supports it, and the difference in dosing and in receptor binding makes the dose transfer far from obvious. Separately: heart failure regimens usually already carry spironolactone or eplerenone, and adding a sartan raises potassium more sharply than in someone with hypertension alone. If azilsartan was prescribed to treat heart failure, consider seeking a second opinion.
- FMoxonidineNot recommended · Centrally acting antihypertensive, imidazoline I1 receptor agonistTreating heart failure by damping sympathetic drive looked logical: noradrenaline runs high when ejection fraction is low, and lowering it promised benefit. The MOXCON trial (Eur J Heart Fail 2003) tested that directly in 1934 patients and stopped early: 54 people died on sustained-release moxonidine against 32 on placebo, with more hospital admissions and more myocardial infarctions as well. Since then moxonidine has no place in heart failure regimens. The AEMPS Moxon label goes further and lists heart failure among the contraindications, alongside bradycardia below 50 beats per minute, sick sinus syndrome and second or third degree AV block. If moxonidine was suggested for the heart in reduced ejection fraction, consider seeking a second opinion.
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