Title:Advances in Heart Failure with Preserved Ejection Fraction Management -
The Role of Sacubitril-Valsartan, Pirfenidone, Spironolactone and Empagliflozin:
Is Success a Series of Small Victories?
Volume: 29
Issue: 7
Author(s): Georgios Giannopoulos*, Maria Kousta, Ioannis Anagnostopoulos, Sofia Karageorgiou, Evangelia Myrovali, Gerasimos Deftereos, Nikolaos Fragakis, Gerasimos Siasos and Vassilios P. Vassilikos
Affiliation:
- 3rd Department of Cardiology, Aristotle University of Thessaloniki, Thessaloniki, Greece
Keywords:
Congestive, preserved, ARNI, neprilysin, angiotensin, mineralocorticoid, SGLT2, inhibitor.
Abstract:
Background: Heart failure with preserved ejection fraction (HFpEF) is a syndrome characterized by
marked heterogeneity in comorbidities and etiopathology substrates, leading to a diverse range of clinical manifestations
and courses. Treatment options have been extremely limited and up to this day, there are virtually no
pharmaceutical agents proven to reduce mortality in these patients.
Objective: The primary objective of this narrative review is to critically summarize existing evidence regarding
the use of Angiotensin Receptor-Neprilysin Inhibitor (ARNI), spironolactone, pirfenidone and empagliflozin in
HFpEF.
Methods: Medline (via PubMed) and Scopus were searched - from inception up to May 2022- using adequately
selected keywords. Additional hand-search was also performed using the references of the articles identified as
relevant (snowball strategy).
Results: Angiotensin Receptor-Neprilysin Inhibitor (ARNI) and spironolactone, despite being very successful
in HFrEF, did not do well in clinical trials of HFpEF, although there appear to be certain subsets of patients
who may derive benefit. Data regarding pirfenidone are limited and come from small trials; as a result, it would
be premature to draw firm conclusions, although it seems improbable that this agent will ever become a mainstay
in the general population of HFpEF patients, while there may be a niche for the drug in individuals with comorbidities
associated with an intense fibrotic activity. Finally, empagliflozin, largely welcomed as the first
agent to have a “positive” randomized clinical trial in HFpEF, does not seem to evade the general pattern of reduced
hospitalizations for HF with no substantial effect on mortality, seen in ARNI and spironolactone HFpEF
trials.
Conclusion: Recent research in drug treatment for HFpEF has resulted in an overall mixed picture, with trials
showing potential benefits from certain classes of drugs, such as sodium-glucose co-transporter 2 inhibitors,
and no benefit from other drugs, which have shown to be effective in patients with reduced ejection fraction.
However, small steps may be the way to go in HFpEF, and success is sometimes just a series of small victories.
