Heart failure medications:
what they are and what they do

Article written and reviewed by Dr Luca Moretti

Heart failure treatment does not consist of a single medication. Today, several drug classes are used that act through different mechanisms: some reduce the risk of hospitalization and death, while others mainly reduce congestion and symptoms. The combination depends on the type of heart failure, ejection fraction, blood pressure, kidney function, potassium levels, heart rhythm, and other coexisting diseases.
The 2026 ESC guidelines introduced important treatment updates: SGLT2 inhibitors and mineralocorticoid receptor antagonists are now foundational therapy for symptomatic heart failure regardless of ejection fraction.

The main drug classes used are:

• SGLT2 inhibitors, such as dapagliflozin and empagliflozin;
• mineralocorticoid receptor antagonists, such as spironolactone, eplerenone and, in selected settings, finerenone;
• beta-blockers with evidence in heart failure;
• ACE inhibitors, ARNIs, or ARBs in heart failure with reduced ejection fraction;
• diuretics to control congestion;
• additional medications indicated only in specific subgroups.

Treatment is tailored to the individual patient and should not be changed independently. Heart failure is a heterogeneous syndrome, and the same treatment regimen is not appropriate for everyone.

Foundational therapy according to the 2026 ESC guidelines

The new European guidelines distinguish foundational medical therapy, meaning treatments with a strong recommendation and demonstrated benefits on hospitalizations and/or mortality. In symptomatic patients, regardless of EF, this foundation includes an SGLT2 inhibitor and a mineralocorticoid receptor antagonist.
In patients with heart failure with reduced ejection fraction, defined in the 2026 ESC guidelines as EF below 50%, foundational therapy also includes a beta-blocker and a medication acting on the renin-angiotensin system: an ACE inhibitor or ARNI, with an ARB when an ACE inhibitor or ARNI is not tolerated.

The goal is not to add one class slowly only after the previous one has reached its maximum dose. The 2026 ESC guidelines indicate that foundational therapies can be started early, with individualized adjustments, and generally titrated every one to two weeks according to symptoms, blood pressure, heart rate, kidney function, and electrolytes.
This approach requires monitoring because some medications can lower blood pressure, change creatinine or potassium levels, or require adjustments in the presence of other conditions.

SGLT2 inhibitors and mineralocorticoid receptor antagonists

Dapagliflozin and empagliflozin belong to the SGLT2 inhibitor class. Originally developed as diabetes medications, they have demonstrated benefits in heart failure even in people without diabetes. They primarily reduce the risk of hospitalization for heart failure and, across the reduced-EF spectrum, also contribute to reducing cardiovascular risk.
They generally do not cause large reductions in blood pressure and are given at a fixed dose, but attention is required to kidney function, genitourinary infections, dehydration, and, in particular circumstances, the risk of ketoacidosis.

Mineralocorticoid receptor antagonists counteract the effects of aldosterone. Spironolactone and eplerenone are steroidal MRAs; finerenone is a nonsteroidal MRA. The 2026 ESC guidelines recommend an MRA in patients with symptomatic heart failure regardless of EF, selecting the agent according to phenotype and clinical context.
These drugs can increase potassium and affect kidney function. For this reason, serum potassium and eGFR should be checked before and after starting treatment or increasing the dose.

Beta-blockers, ACE inhibitors, ARNIs, and ARBs in HFrEF

Beta-blockers with evidence in heart failure, including bisoprolol, carvedilol, and metoprolol succinate, reduce adrenergic activation and, in stable patients with HFrEF, reduce hospitalizations and mortality. They are generally started at low doses and increased progressively. They should not be started or up-titrated without caution during hemodynamic instability or marked congestion.
Heart rate may decrease, and some people initially experience fatigue or dizziness, but this does not automatically mean that the medication should be stopped.

ACE inhibitors, ARBs, and ARNIs act on the renin-angiotensin system. The ARNI sacubitril/valsartan combines an angiotensin receptor blocker with neprilysin inhibition. In symptomatic HFrEF, the 2026 ESC guidelines recommend an ACE inhibitor or ARNI and recommend switching from an ACE inhibitor or ARB to an ARNI when appropriate; an ARB is an alternative when an ACE inhibitor or ARNI is not tolerated.
Blood pressure, kidney function, and potassium guide initiation and titration. An ACE inhibitor and an ARNI must not be taken at the same time, and switching requires an appropriate interval to reduce the risk of angioedema.

Diuretics: why they improve symptoms but do not replace foundational therapy

Loop diuretics, such as furosemide and torsemide, are used when congestion, edema, or fluid accumulation in the lungs is present. By increasing sodium and water excretion, they can rapidly reduce swelling and breathlessness.
The 2026 ESC guidelines recommend a dynamic, individualized dose based on volume status. The goal is to use the lowest dose needed to maintain euvolemia, because excessive diuretic therapy can promote dehydration, hypotension, electrolyte abnormalities, and worsening kidney function.

Diuretics are therefore essential for symptom control, but they should not be confused with treatments that modify the course of the disease. If foundational therapy works well and congestion decreases, diuretic requirements may fall over time.
Chronic addition of thiazide diuretics is not routine in stable patients; more intensive combinations are mainly used in cases of diuretic resistance and require close monitoring.

Other medications that may be added in selected cases

Some patients require additional treatments. Ivabradine may be considered in HFrEF with markedly reduced EF, sinus rhythm, and persistently elevated heart rate despite a beta-blocker at the tolerated dose. Digoxin or digitoxin may be considered in some symptomatic patients to reduce the risk of hospitalization. Vericiguat may be used in certain patients with recent or persistent worsening despite optimized therapy.
The hydralazine-isosorbide dinitrate combination has specific indications, including some patients who do not tolerate ACE inhibitors, ARNIs, or ARBs and certain subgroups with HFrEF.

The presence of atrial fibrillation, ischemic heart disease, diabetes, obesity, kidney disease, or valvular heart disease may require additional medications that are not strictly "heart failure drugs" but are essential for treating its causes and comorbidities.
For the same reason, it is important to tell the doctor about over-the-counter medicines, supplements, and herbal products as well: some can worsen fluid retention, blood pressure, or kidney function. These aspects are discussed in more detail in the guide to medications to avoid or use with caution in heart failure.

Frequently asked questions about heart failure medications

What are the main medications for heart failure?
In the 2026 ESC guidelines, SGLT2 inhibitors and mineralocorticoid receptor antagonists are part of foundational therapy for symptomatic heart failure regardless of ejection fraction. In HFrEF, foundational therapy also includes beta-blockers and an ACE inhibitor, ARNI, or ARB.

Do diuretics treat heart failure?
Diuretics are essential for reducing congestion, edema, and breathlessness when fluid retention is present. Their main role is to control symptoms and volume status; they do not replace medications that modify the course of the disease.

Are SGLT2 inhibitors useful even if you do not have diabetes?
Yes. Dapagliflozin and empagliflozin have shown benefits in heart failure regardless of whether diabetes is present, and in the 2026 ESC guidelines they are recommended in patients with symptomatic heart failure across the entire spectrum of ejection fraction.

Why are several medications used together in heart failure?
Because they act on different mechanisms and their benefits are additive. In heart failure with reduced ejection fraction, early combination of the different foundational drug classes reduces the risk of hospitalization and death more than a single isolated therapy.

If ejection fraction improves, can the medications be stopped?
Generally no. The 2026 ESC guidelines recommend continuing foundational therapy at the highest tolerated doses even in patients who become asymptomatic or show improvement in ejection fraction, except in selected situations assessed by a specialist.