What are recent developments in heart failure treatment?

From the Guidelines

Recent developments in heart failure treatment prioritize a "quadruple therapy" approach, incorporating beta-blockers, mineralocorticoid receptor antagonists, SGLT2 inhibitors, and either ACE inhibitors/ARBs or sacubitril/valsartan as foundational treatment, as supported by the most recent study from 2024 1. The management of heart failure has evolved significantly, with a focus on reducing morbidity, mortality, and improving quality of life. Key advancements include the use of SGLT2 inhibitors, such as empagliflozin and dapagliflozin, which have demonstrated benefits in reducing hospitalizations and mortality in patients with heart failure, regardless of ejection fraction status 1.

Recent Treatment Advances

• The combination drug sacubitril/valsartan has shown superior outcomes compared to ACE inhibitors alone in heart failure with reduced ejection fraction, as reported in the 2021 update to the ACC expert consensus decision pathway for optimization of heart failure treatment 1.
• Guideline-directed medical therapy now emphasizes the importance of managing comorbidities, such as atrial fibrillation, iron deficiency, and sleep apnea, to improve heart failure outcomes 1.
• The use of SGLT2 inhibitors in patients with heart failure with preserved ejection fraction (HFpEF) has been shown to reduce composite cardiovascular death or HF hospitalizations, as demonstrated in recent randomized controlled trials 1.

Management of HFpEF

• The management of HFpEF has largely focused on symptom improvement, reducing congestion with diuretics, and treating cardiovascular and non-cardiovascular comorbidities 1.
• Updated clinical practice guidelines on HFpEF have been published in recent years, highlighting the importance of SGLT2 inhibitors in the treatment of this condition 1.

Key Takeaways

• The "quadruple therapy" approach is now the recommended foundational treatment for heart failure patients, as supported by the most recent study from 2024 1.
• SGLT2 inhibitors have shown significant benefits in reducing hospitalizations and mortality in patients with heart failure, regardless of ejection fraction status 1.
• Managing comorbidities, such as atrial fibrillation, iron deficiency, and sleep apnea, is crucial to improving heart failure outcomes 1.

From the FDA Drug Label

The primary objective of PARADIGM-HF was to determine whether sacubitril and valsartan, a combination of sacubitril and an RAS inhibitor (valsartan), was superior to an RAS inhibitor (enalapril) alone in reducing the risk of the combined endpoint of cardiovascular (CV) death or hospitalization for heart failure (HF) PARADIGM-HF demonstrated that sacubitril and valsartan, a combination of sacubitril and an RAS inhibitor (valsartan), was superior to and RAS inhibitor (enalapril), in reducing the risk of the combined endpoint of cardiovascular death or hospitalization for heart failure, based on a time-to-event analysis (hazard ratio [HR] 0.80; 95% confidence interval [CI], 0.73,0.87, p <0. 0001) SHIFT demonstrated that ivabradine reduced the risk of the combined endpoint of hospitalization for worsening heart failure or cardiovascular death based on a time-to-event analysis (hazard ratio: 0.82,95% confidence interval [CI]: 0.75,0.90, p < 0. 0001)

Recent developments in heart failure treatment include the use of sacubitril and valsartan and ivabradine, which have been shown to reduce the risk of cardiovascular death or hospitalization for heart failure in clinical trials, such as PARADIGM-HF 2 and SHIFT 3.

• Sacubitril and valsartan have been demonstrated to be superior to enalapril in reducing the risk of cardiovascular death or hospitalization for heart failure.
• Ivabradine has been shown to reduce the risk of hospitalization for worsening heart failure. Key benefits of these treatments include:
• Reduced risk of cardiovascular death
• Reduced risk of hospitalization for heart failure It is essential to consider these developments when making clinical decisions for patients with heart failure.

From the Research

Recent Developments in Heart Failure Treatment

• The treatment of heart failure with reduced ejection fraction (HFrEF) has undergone significant developments in recent years, with a focus on neurohormonal modulation and the use of novel agents 4, 5, 6.
• Angiotensin Converting Enzyme (ACE) inhibitors or Angiotensin Receptor Blockers (ARBs) and Beta Blockers (BB) are currently recommended by guidelines for the treatment of HFrEF 4.
• Newer medications, such as sacubitril/valsartan, which combines an ARB with a neprilysin inhibitor, have shown benefits in mortality and can be used in place of an ACE inhibitor or an ARB 4, 5.
• Sodium-glucose cotransporter 2 (SGLT2) inhibitors, such as dapagliflozin, have also been shown to improve outcomes in patients with HFrEF, regardless of their diabetic status 4, 6.
• Other agents, such as ivabradine, hydralazine/isosorbide dinitrate, digoxin, and vericiguat, have been shown to have beneficial effects in selected patients with HFrEF 5, 6, 7.

Treatment Options for HFrEF

• The core medical therapies for patients with HFrEF include ACE inhibitors or ARBs, beta blockers, mineralocorticoid receptor antagonists, and SGLT2 inhibitors 6.
• Sacubitril/valsartan and dapagliflozin have emerged as key players in the treatment of HFrEF, with benefits in mortality and morbidity 4, 5, 6.
• Hydralazine and nitrates may have a role in bridging the survival gap in Black patients with HFrEF, particularly when added to standard therapy 7.
• The combination of hydralazine and nitrates may also be useful in patients with contraindications to ACE inhibitors, ARBs, and sacubitril/valsartan 7.

Ongoing Research and Future Directions

• Further research is needed to fully understand the mechanisms of action of newer agents, such as sacubitril/valsartan and dapagliflozin, and to determine their optimal use in clinical practice 4, 6.
• Ongoing studies are exploring the potential benefits of other novel agents, such as vericiguat, in the treatment of HFrEF 6.
• The development of new treatments for HFrEF is an active area of research, with a focus on improving outcomes and reducing morbidity and mortality in patients with this condition 4, 5, 6.