Sacubitril-Valsartan vs. Valsartan in HFpEF Patients

Core Concepts

Sacubitril-valsartan shows greater reduction in natriuretic peptides in HFpEF patients.

Abstract

The PARAGLIDE-HF trial compared sacubitril-valsartan (Entresto) and valsartan (Diovan) in HFpEF patients with an EF >40%. Here are the key highlights and insights:

• Study Details:
  • 466 patients with EF >40% enrolled.
  • Median age 71, 52% women, 22% Black.
• Primary Endpoint:
  • Greater reduction in NT-proBNP with sacubitril-valsartan.
• Secondary Outcomes:
  • Favorable outcomes for sacubitril-valsartan.
• Adverse Effects:
  • Reduced worsening renal function but increased symptomatic hypotension.
• Subgroup Analysis:
  • Larger treatment effect in patients with EF ≤60%.
• Expert Comments:
  • Positive outlook on ARNI use in HF patients.
• Editorial Concerns:
  • Margin of benefit less than expected.
  • Data not conclusive, caution advised in ARNI use.

Stats

The time-averaged reduction in NT-proBNP was greater with sacubitril-valsartan, with a change ratio of 0.85 (15% greater reduction).
Sacubitril-valsartan reduced worsening renal function compared to valsartan (odds ratio, 0.61) but increased symptomatic hypotension (OR, 1.73).

Quotes

"Hopefully, these trial data help strengthen clinicians' resolve to prescribe sacubitril/valsartan to a growing population of vulnerable patients." - Sean Pinney, MD
"Clinicians who elect to use sacubitril-valsartan in this population should be mindful of the risk for hypotension and select patients carefully." - Editorial

Key Insights Distilled From

ARNI Bests ARB to Reduce NT-proBNP in Stabilized HFpEF

by Marilynn Lar... at www.medscape.com 05-25-2023

https://www.medscape.com/viewarticle/992461

Deeper Inquiries

How might the findings of this trial impact the treatment guidelines for HFpEF patients?

The findings of this trial could potentially impact the treatment guidelines for HFpEF patients by suggesting a potential benefit of using sacubitril-valsartan (ARNI) over valsartan (ARB) in certain subgroups of patients. Specifically, the trial showed a greater reduction in natriuretic peptides and less worsening renal function with sacubitril-valsartan, indicating potential cardiovascular and renal benefits. This could lead to a consideration of ARNI therapy in HFpEF patients with an ejection fraction (EF) greater than 40% to less than or equal to 60%. The data may influence future guidance on the use of sacubitril-valsartan in HF patients, regardless of the chronicity of HF or the treatment setting.

What are the potential implications of the increased symptomatic hypotension observed with sacubitril-valsartan?

The increased symptomatic hypotension observed with sacubitril-valsartan in the trial could have several potential implications. Hypotension can lead to symptoms such as dizziness, lightheadedness, and fainting, which may impact the tolerability and adherence to the medication. Clinicians need to be aware of this side effect and carefully monitor patients for signs of hypotension when initiating sacubitril-valsartan therapy. Optimizing volume status and adjusting background therapies, such as dose reduction or discontinuation of calcium channel blockers in patients with lower baseline blood pressures, may help prevent hypotension events. Close monitoring and follow-up are essential to manage hypotension and ensure patient stability and adherence to treatment.

How can the concerns raised in the editorial regarding the conclusive nature of the data be addressed in future research?

To address the concerns raised in the editorial regarding the conclusive nature of the data in future research, several steps can be taken. Firstly, future studies should aim to provide a more robust assessment of the clinical benefits of sacubitril-valsartan in HFpEF patients with a recent episode of worsening HF. This could involve larger sample sizes, longer follow-up periods, and more comprehensive outcome measures to evaluate the efficacy and safety of ARNI therapy. Additionally, future research should report diuretic dosing in both treatment groups to account for potential confounding factors that may influence outcomes such as NT-proBNP reduction and hypotension rates. Minimizing missing data and ensuring data integrity through rigorous study protocols and monitoring can help improve the reliability and validity of the results. By addressing these methodological and analytical considerations, future research can provide more conclusive evidence on the use of sacubitril-valsartan in HFpEF patients.