Medical Therapies for Heart Failure With Preserved Ejection Fraction.

Area of Science:

• Cardiology
• Pharmacology
• Internal Medicine

Background:

• Cardiovascular pharmacotherapy often targets the renin-angiotensin-aldosterone system (RAAS).
• RAAS overactivation is implicated across cardiovascular diseases, including hypertension and heart failure.
• Previous trials in heart failure with preserved ejection fraction (HFpEF) have not shown added benefit of RAAS blockade.

Purpose of the Study:

• To reappraise previous clinical trials on RAAS blockade in HFpEF.
• To explore reasons for the lack of efficacy in HFpEF trials.
• To advocate for the use of RAAS blockers in HFpEF based on broader evidence.

Main Methods:

• Review and critical analysis of four prospective, randomized, placebo-controlled clinical trials in HFpEF.
• Evaluation of the PARAGON-HF trial comparing sacubitril-valsartan to valsartan.
• Consideration of evidence from hypertension and heart failure with reduced ejection fraction (HFrEF) trials.

Main Results:

• Four major trials of RAAS blockade in HFpEF did not demonstrate statistically significant efficacy when added to existing therapies.
• The PARAGON-HF trial also failed to show improved outcomes with dual RAAS blockade compared to valsartan alone.
• RAAS blockade has shown positive outcomes in hypertension and HFrEF, highlighting a discrepancy in HFpEF.

Conclusions:

• Despite negative trial results in HFpEF, the established efficacy of RAAS blockers in hypertension and HFrEF warrants their consideration.
• Weaknesses in previous HFpEF trials may have obscured potential benefits.
• RAAS blockers, including mineralocorticoid receptor antagonists (MRAs), should be considered for treating patients with HFpEF.