Drugs used in congestive heart failure (CHF)

Drugs used in congestive heart failure (CHF) are organized around guideline-directed medical therapy that improves survival and reduces hospitalizations, complemented by symptom‑relief agents and phenotype‑specific options across HFrEF, HFmrEF, and HFpEF.

Core goals

Pharmacotherapy in CHF aims to relieve congestion, halt or reverse maladaptive neurohormonal activation, prevent disease progression, and lower cardiovascular death and HF rehospitalization. Foundational therapy in HFrEF combines renin–angiotensin system blockade (preferably ARNI), evidence‑based beta‑blocker, mineralocorticoid receptor antagonist, and an SGLT2 inhibitor, with diuretics added for volume control.

Phenotypes and staging

Guidelines classify HF by left ventricular ejection fraction into HFrEF (≤40%), HFmrEF (41–49%), HFpEF (≥50%), and improved LVEF (HFimpEF) for previously reduced EF now >40%. Patients with HFimpEF should continue full GDMT to prevent relapse despite recovery of EF. Stages A–D emphasize risk, pre‑HF, symptomatic HF, and advanced HF with recommendations spanning prevention to specialized care.

Foundational HFrEF therapy

The contemporary HFrEF standard is quadruple therapy: ARNI (or ACEi/ARB if ARNI not feasible), beta‑blocker (carvedilol, bisoprolol, or metoprolol succinate), MRA (spironolactone or eplerenone), and an SGLT2 inhibitor (dapagliflozin or empagliflozin). This combination lowers mortality and HF hospitalizations and should be initiated and up‑titrated promptly to maximally tolerated doses.

Diuretics for congestion

Loop diuretics are first‑line for euvolemic restoration, symptom relief, and prevention of decompensation, with furosemide, bumetanide, or torsemide dosed and titrated to maintain the lowest dose that controls weight and edema. Dose equivalence is furosemide 40 mg ≈ bumetanide 1 mg ≈ torsemide 20 mg, and combinations with metolazone or IV strategies are reserved for diuretic resistance with close electrolyte and renal monitoring. Guidelines endorse diuretics across HF phenotypes to relieve congestion (Class I), while background disease‑modifying therapy reduces long‑term diuretic needs.

ACE inhibitors

ACE inhibitors reduce angiotensin II and degrade bradykinin, providing arterial and venous dilation, favorable remodeling, and improved survival in HFrEF when ARNI is not feasible. Start low and titrate every few weeks toward target doses (e.g., enalapril 10–20 mg BID, lisinopril 20–30 mg daily), monitoring creatinine and potassium and holding for significant hyperkalemia or angioedema.

ARBs

ARBs are alternatives when ACE inhibitors are not tolerated, with target doses such as valsartan 160 mg BID or candesartan 32 mg daily, and similar precautions for renal function and potassium. In HFpEF, ARBs have inconsistent outcome effects and are mainly used to manage comorbid hypertension or kidney disease rather than mortality benefit.

ARNIs (sacubitril/valsartan)

Sacubitril/valsartan outperforms ACE inhibition by further reducing CV death and HF hospitalization in HFrEF and is recommended for symptomatic patients, replacing ACEi/ARB when tolerated. Start at 49/51 mg BID (or 24/26 mg BID in low‑dose or naive patients), ensure a 36‑hour washout after ACE inhibitor, and watch for hypotension, renal dysfunction, hyperkalemia, and angioedema.

Beta‑blockers

Evidence‑based beta‑blockers reduce mortality and hospitalizations in HFrEF and should be initiated when euvolemic, then titrated to target (e.g., carvedilol up to 25–50 mg BID, metoprolol succinate up to 200 mg daily, bisoprolol up to 10 mg daily). Avoid initiation during acute decompensation, and continue during exacerbations when possible with diuretic optimization to maintain long‑term benefits.

MRAs (spironolactone, eplerenone)

MRAs reduce sudden death and HF events in HFrEF and are recommended when eGFR >30 mL/min/1.73 m² and K+ <5.0 mEq/L, with frequent monitoring during initiation and titration. Typical doses are spironolactone 25–50 mg daily or eplerenone 25–100 mg daily, with gynecomastia less frequent on eplerenone and higher hyperkalemia risk when combined with ACEi/ARB/ARNI.

SGLT2 inhibitors

Dapagliflozin and empagliflozin reduce HF hospitalizations and CV mortality in symptomatic HFrEF irrespective of diabetes and are recommended as part of foundational therapy. ESC updates elevate SGLT2 inhibitors to Class I across HFmrEF and HFpEF for prevention of HF hospitalization and composite outcomes, reflecting DELIVER and EMPEROR‑Preserved trial data.

Hydralazine–isosorbide dinitrate

This combination provides added mortality benefit in HFrEF, particularly in patients of African ancestry on background ACEi/ARB/ARNI, beta‑blocker, and MRA, or when renin–angiotensin blockade is not tolerated. Avoid coadministration with phosphodiesterase‑5 inhibitors due to hypotension risk.

Ivabradine

Ivabradine lowers heart rate by If current inhibition and is reasonable in HFrEF with sinus rhythm and HR >70 bpm despite maximally tolerated beta‑blocker, improving HF hospitalizations and symptoms. Typical dosing is 2.5–5 mg BID titrated to a resting HR 50–60 bpm, avoiding use in atrial fibrillation or absent sinus rhythm.

Digoxin

Digoxin offers symptomatic relief and reduced hospitalizations in HFrEF without mortality benefit, and its use has narrowed to persistent symptoms on GDMT or rate control in concomitant atrial fibrillation. Low dosing (e.g., 0.125 mg daily, lower in CKD, elderly, or low body mass) targets trough 0.8–1.2 ng/mL, with vigilance for toxicity, especially with renal dysfunction or electrolyte derangements.

Vericiguat and newer options

Soluble guanylate cyclase stimulation with vericiguat may be considered in high‑risk HFrEF with recent decompensation to reduce composite events, though guideline positioning is secondary to foundational therapy. Budget impact analyses suggest minimal system‑wide cost additions, but adoption remains selective and evidence is evolving compared with core quadruple therapy.

Iron repletion

Intravenous iron improves symptoms and quality of life in iron‑deficient HFrEF/HFmrEF, and ESC updates strengthen recommendations for IV ferric carboxymaltose or ferric derisomaltose to reduce HF hospitalizations. Benefits on mortality remain uncertain, and selection hinges on ferritin and transferrin saturation assessment with repeat dosing as needed.

HFpEF pharmacotherapy

In HFpEF, SGLT2 inhibitors receive Class I recommendation to reduce HF hospitalizations, while MRAs and ARNI may be considered to reduce admissions in those at the lower EF spectrum. Comorbidity management, blood pressure control, atrial fibrillation management, and decongestion remain central because survival benefit with conventional neurohormonal blockade is less consistent.

HFmrEF approach

SGLT2 inhibitors reduce events and are recommended, with beta‑blockers, ARNI/ACEi/ARB, and MRAs reasonable to consider particularly when EF is toward the lower range. The therapeutic strategy mirrors HFrEF in many cases, with ESC emphasizing the cross‑phenotype benefit of SGLT2 inhibition and rapid optimization.

Acute decompensated strategies

Hospitalized decompensation is managed with IV loop diuretics, careful escalation for diuretic resistance (e.g., metolazone or continuous infusion), and early SGLT2 initiation when stable as supported by EMPULSE. ESC commentary highlights acetazolamide and hydrochlorothiazide add‑on strategies improving decongestion endpoints, though broader outcome benefits and routine class recommendations are pending.

Titration and sequencing

Evidence and recent implementation science favor rapid initiation of all four HFrEF pillars at tolerable low doses, then up‑titration toward targets in weeks rather than months, especially around hospital discharge. An intensive optimization pathway with frequent early follow‑up reduced rehospitalization and death in STRONG‑HF and has been incorporated into ESC updates as a Class I recommendation.

Monitoring and safety

Across RAAS blockade, ARNIs, and MRAs, monitor serum creatinine and potassium at baseline, 1–2 weeks after starts or dose changes, and periodically thereafter, adjusting for hyperkalemia or renal deterioration. Beta‑blocker titration requires euvolemia and attention to bradycardia or hypotension, while loop diuretic escalation mandates daily or frequent electrolyte and renal checks during aggressive diuresis.

Special populations

In CKD, MRAs require cautious selection (eGFR >30 and K+ <5.0), and ARNI/ACEi/ARB dosing must accommodate renal function with close labs and temporary holds during intercurrent illness. In HF with AF, beta‑blockers and digoxin are used for rate control, and anticoagulation is guided by stroke risk, while in cardiac amyloidosis, guideline‑endorsed tafamidis is disease‑modifying rather than HF‑directed neurohormonal blockade.

Patient education and adherence

Clear instructions on daily dosing, non‑interruption of life‑saving drugs, recognition of side effects, and sick‑day rules reduce preventable decompensations and adverse events. Weight‑based self‑adjustment of diuretics in reliable patients and prompt contact for refractory weight gain are standard best practices.

Practical drug selection by phenotype

• HFrEF: ARNI (or ACEi/ARB), beta‑blocker, MRA, SGLT2 inhibitor for mortality/hospitalization reduction; add diuretics for congestion and consider ivabradine, hydralazine–nitrate, digoxin, IV iron, or vericiguat as indicated.
• HFmrEF: SGLT2 inhibitor recommended; consider ARNI/ACEi/ARB, beta‑blocker, and MRA especially near lower EF.
• HFpEF: SGLT2 inhibitor recommended; consider MRA and ARNI to reduce hospitalizations, with strict comorbidity control and diuretic use for congestion.

Doses and targets (illustrative)

Representative targets include sacubitril/valsartan 97/103 mg BID as tolerated with 36‑hour ACEi washout, carvedilol up to 25–50 mg BID, metoprolol succinate up to 200 mg daily, spironolactone 25–50 mg daily, and eplerenone 50–100 mg daily. Loop diuretic equivalence (furosemide 40 mg ≈ bumetanide 1 mg ≈ torsemide 20 mg) aids conversions, and ivabradine is titrated to HR 50–60 bpm when indicated.

HF therapeutics summary table

SEO quick answers

• Best medications for HFrEF: sacubitril/valsartan or ACEi/ARB, carvedilol or metoprolol succinate or bisoprolol, spironolactone or eplerenone, and dapagliflozin or empagliflozin.
• Drugs for HFpEF: SGLT2 inhibitors with consideration of MRA and ARNI to reduce hospitalizations; emphasize blood pressure and AF control.
• Diuretic of choice: loop diuretics with dose equivalence furosemide 40 mg ≈ bumetanide 1 mg ≈ torsemide 20 mg; add thiazide‑type agents only for resistance.
• When to use ivabradine or digoxin: ivabradine in sinus rhythm HR >70 bpm on maximized beta‑blocker; digoxin for persistent symptoms or AF rate control with careful monitoring.

Textbook and guideline alignment

Merck Manual Professional consolidates drug class mechanisms, dosing, and monitoring across phenotypes and remains a practical “textbook” reference for daily CHF pharmacotherapy. 

The 2022 AHA/ACC/HFSA HF guideline and ESC 2023 update define the evidence‑based classes, recommendations, and rapid optimization strategies that inform modern GDMT and phenotype‑specific care.

Advanced and special therapy notes

• Hydralazine–ISDN provides high‑value benefit in appropriate HFrEF subsets on top of GDMT.
• IV iron is upgraded in ESC guidance for symptomatic improvement and reduced HF hospitalizations in iron‑deficient HFrEF/HFmrEF.
• Post‑discharge intensive up‑titration pathways (e.g., STRONG‑HF) lower combined death/HF rehospitalization and are now Class I in ESC updates.

Practical implementation pearls

Start low and go fast across pillars with close labs and vitals, prioritizing full regimen initiation over single‑class maximization when stability allows. During acute decompensation, focus on IV diuresis, decongestion strategies, and early SGLT2 initiation when stable, transitioning to outpatient rapid titration and frequent follow‑up.

Authoritative sources behind this chapter

• 2022 AHA/ACC/HFSA Guideline and official slide/top‑10 materials for GDMT classes and phenotype recommendations.
• ESC 2023 focused update commentary for SGLT2 across EF spectrum, IV iron, diuretic combinations, and STRONG‑HF optimization.
• Merck Manual Professional for drug mechanisms, titration, dose targets, equivalence, and monitoring.