What medication is used to treat moderate to severe heart failure?

From the Guidelines

The most effective treatment for moderate to severe heart failure includes ACE inhibitors or ARBs, beta-blockers, diuretics, and aldosterone antagonists, with sacubitril/valsartan being a superior option to ACE inhibitors alone in reducing mortality. The treatment of heart failure is multifaceted and involves a combination of medications to reduce morbidity, mortality, and improve quality of life.

• The cornerstone treatments include:
  • ACE inhibitors (like lisinopril, enalapril) or ARBs (such as losartan, valsartan) which reduce strain on the heart by relaxing blood vessels 1.
  • Beta-blockers (carvedilol, metoprolol succinate, bisoprolol) slow heart rate and reduce workload 1.
  • Diuretics (furosemide, bumetanide) help remove excess fluid 1.
• For moderate to severe cases, additional medications are typically added, including:
  • Aldosterone antagonists (spironolactone, eplerenone) which block hormones that cause salt retention 1.
  • Newer agents like SGLT2 inhibitors (dapagliflozin, empagliflozin) which improve outcomes by multiple mechanisms 1.
• In advanced cases, inotropes (dobutamine, milrinone) may be used temporarily to strengthen heart contractions.
• Sacubitril/valsartan (Entresto) combines an ARB with a neprilysin inhibitor and has shown superior results to ACE inhibitors alone in reducing mortality 1. Treatment is typically lifelong and requires careful monitoring of kidney function, electrolytes, and blood pressure, with dose adjustments as needed. These medications work together to reduce the heart's workload, improve pumping efficiency, prevent fluid buildup, and ultimately slow disease progression and reduce hospitalizations and mortality. The most recent and highest quality study 1 supports the use of these medications in the treatment of heart failure, and the use of sacubitril/valsartan is recommended as a replacement for an ACE-I to further reduce the risk of HF hospitalization and death in ambulatory patients with HFrEF who remain symptomatic despite optimal treatment with an ACE-I, a beta-blocker and an MRA.

From the FDA Drug Label

In the Valsartan Heart Failure Trial (Val-HeFT), comparing valsartan in total daily doses up to 320 mg (n=2,506) to placebo (n=2,494), 10% of valsartan patients discontinued for adverse reactions vs. 7% of placebo patients The table shows adverse reactions in double-blind short-term heart failure trials, including the first 4 months of the Valsartan Heart Failure Trial, with an incidence of at least 2% that were more frequent in valsartan-treated patients than in placebo-treated patients All patients received standard drug therapy for heart failure, frequently as multiple medications, which could include diuretics, digitalis, beta-blockers. About 93% of patients received concomitant ACE inhibitors Valsartan (n=3,282) Placebo (n=2,740) Dizziness 17% 9% Hypotension 7% 2% Diarrhea 5% 4% Arthralgia 3% 2% Fatigue 3% 2% Back Pain 3% 2% Dizziness, postural 2% 1% Hyperkalemia 2% 1% Hypotension, postural 2% 1%

Valsartan is used for heart failure that is moderate to severe 2.

• Key points:
  • Valsartan has been evaluated for safety in heart failure trials.
  • The incidence of adverse reactions was similar to placebo.
  • Common adverse reactions included dizziness, hypotension, diarrhea, arthralgia, fatigue, and back pain.
  • Valsartan can be used in combination with other medications, such as ACE inhibitors, diuretics, digitalis, and beta-blockers.

From the Research

Medications for Moderate to Severe Heart Failure

• Aldosterone antagonists (or mineralocorticoid receptor antagonists [MRAs]) are recommended for patients with moderate to severe heart failure symptoms and reduced left ventricular ejection fraction (LVEF) 3.
• Angiotensin receptor blockers (ARBs) can be used as substitutes for ACE inhibitors in patients who have true ACE inhibitor intolerance, or as additive therapy in patients on maximal ACE inhibitor therapy who remain symptomatic 4.
• Combined angiotensin receptor antagonists and neprilysin inhibitors have been shown to improve the prognosis of patients with heart failure with reduced ejection fraction 5.
• Treatment strategies for heart failure with reduced ejection fraction (HFrEF) include the use of:
  • β-blockers
  • Angiotensin receptor-neprilysin inhibitors
  • Angiotensin-converting enzyme inhibitors
  • Angiotensin receptor blockers
  • Mineralocorticoid receptor antagonists
  • Ivabradine
  • Hydralazine/isosorbide dinitrate
  • Sodium-glucose cotransporter 2 (SGLT2) inhibitors
  • Vericiguat, a soluble guanylate cyclase stimulator 6.
• Angiotensin-converting enzyme inhibitors (ACEi) and angiotensin-receptor blockers (ARB) have been shown to reduce mortality and hospitalization risk in patients with acute decompensated heart failure 7.