Heart Failure with Preserved Ejection Fraction: a Pharmacotherapeutic Update

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Abstract

While guidelines for management of heart failure with reduced ejection fraction (HFrEF) are consensual and have led to improved survival, treatment options for heart failure with preserved ejection fraction (HFpEF) remain limited and aim primarily for symptom relief and improvement of quality of life. Due to the shortage of therapeutic options, several drugs have been investigated in multiple clinical trials. The majority of these trials have reported disappointing results and have suggested that HFpEF might not be as simply described by ejection fraction as previously though. In fact, HFpEF is a complex clinical syndrome with various comorbidities and overlapping distinct phenotypes that could benefit from personalized therapeutic approaches. This review summarizes the results from the most recent phase III clinical trials for HFpEF and the most promising drugs arising from phase II trials as well as the various challenges that are currently holding back the development of new pharmacotherapeutic options for these patients.

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Most cited references 107

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Angiotensin–Neprilysin Inhibition versus Enalapril in Heart Failure

John J.V. McMurray, Milton Packer, Akshay S Desai … (2014)

We compared the angiotensin receptor-neprilysin inhibitor LCZ696 with enalapril in patients who had heart failure with a reduced ejection fraction. In previous studies, enalapril improved survival in such patients. In this double-blind trial, we randomly assigned 8442 patients with class II, III, or IV heart failure and an ejection fraction of 40% or less to receive either LCZ696 (at a dose of 200 mg twice daily) or enalapril (at a dose of 10 mg twice daily), in addition to recommended therapy. The primary outcome was a composite of death from cardiovascular causes or hospitalization for heart failure, but the trial was designed to detect a difference in the rates of death from cardiovascular causes. The trial was stopped early, according to prespecified rules, after a median follow-up of 27 months, because the boundary for an overwhelming benefit with LCZ696 had been crossed. At the time of study closure, the primary outcome had occurred in 914 patients (21.8%) in the LCZ696 group and 1117 patients (26.5%) in the enalapril group (hazard ratio in the LCZ696 group, 0.80; 95% confidence interval [CI], 0.73 to 0.87; P<0.001). A total of 711 patients (17.0%) receiving LCZ696 and 835 patients (19.8%) receiving enalapril died (hazard ratio for death from any cause, 0.84; 95% CI, 0.76 to 0.93; P<0.001); of these patients, 558 (13.3%) and 693 (16.5%), respectively, died from cardiovascular causes (hazard ratio, 0.80; 95% CI, 0.71 to 0.89; P<0.001). As compared with enalapril, LCZ696 also reduced the risk of hospitalization for heart failure by 21% (P<0.001) and decreased the symptoms and physical limitations of heart failure (P=0.001). The LCZ696 group had higher proportions of patients with hypotension and nonserious angioedema but lower proportions with renal impairment, hyperkalemia, and cough than the enalapril group. LCZ696 was superior to enalapril in reducing the risks of death and of hospitalization for heart failure. (Funded by Novartis; PARADIGM-HF ClinicalTrials.gov number, NCT01035255.).

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Empagliflozin in Heart Failure with a Preserved Ejection Fraction

Stefan D. Anker, Javed Butler, Gerasimos Filippatos … (2022)

Sodium-glucose cotransporter 2 inhibitors reduce the risk of hospitalization for heart failure in patients with heart failure and a reduced ejection fraction, but their effects in patients with heart failure and a preserved ejection fraction are uncertain.

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Angiotensin–Neprilysin Inhibition in Heart Failure with Preserved Ejection Fraction

Scott D. Solomon, John J.V. McMurray, Inder S Anand … (2020)

The angiotensin receptor-neprilysin inhibitor sacubitril-valsartan led to a reduced risk of hospitalization for heart failure or death from cardiovascular causes among patients with heart failure and reduced ejection fraction. The effect of angiotensin receptor-neprilysin inhibition in patients with heart failure with preserved ejection fraction is unclear.

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Author and article information

Contributors

Pedro Vaz-Salvador:

ORCID: http://orcid.org/0000-0001-9511-9431

pedro.salvador.98@outlook.com

Rui Adão:

ORCID: http://orcid.org/0000-0003-2203-436X

ruiadao@med.up.pt

Inês Vasconcelos:

ORCID: http://orcid.org/0000-0002-4870-9946

inesfvasconcelos@gmail.com

Adelino F. Leite-Moreira:

ORCID: http://orcid.org/0000-0001-7808-3596

a.f.leitemoreira@gmail.com

Carmen Brás-Silva:

ORCID: http://orcid.org/0000-0003-1527-3776

carmensb@med.up.pt

Journal

Journal ID (nlm-ta): Cardiovasc Drugs Ther

Journal ID (iso-abbrev): Cardiovasc Drugs Ther

Title: Cardiovascular Drugs and Therapy

Publisher: Springer US (New York )

ISSN (Print): 0920-3206

ISSN (Electronic): 1573-7241

Publication date (Electronic): 31 January 2022

Pages: 1-18

Affiliations

[1 ]GRID grid.5808.5, ISNI 0000 0001 1503 7226, Department of Surgery and Physiology, Faculty of Medicine, , Cardiovascular Research and Development Center - UnIC, University of Porto, Alameda Prof. Hernâni Monteiro, ; 4200-319 Porto, Portugal

[2 ]GRID grid.5808.5, ISNI 0000 0001 1503 7226, Faculty of Nutrition and Food Sciences, , University of Porto, Rua Do Campo Alegre, ; 823 4150-180 Porto, Portugal

Author information

Pedro Vaz-Salvador http://orcid.org/0000-0001-9511-9431

Rui Adão http://orcid.org/0000-0003-2203-436X

Inês Vasconcelos http://orcid.org/0000-0002-4870-9946

Adelino F. Leite-Moreira http://orcid.org/0000-0001-7808-3596

Carmen Brás-Silva http://orcid.org/0000-0003-1527-3776

Article

Publisher ID: 7306

DOI: 10.1007/s10557-021-07306-8

PMC ID: 8801287

PubMed ID: 35098432

SO-VID: 815b3337-20ee-479a-b461-b9b7280d6bf9

License:

This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

History

Date accepted : 17 December 2021

Funding

Funded by: FundRef http://dx.doi.org/10.13039/501100001871, Fundação para a Ciência e a Tecnologia;

Award ID: UIDB/00051/2020

Award ID: UIDP/00051/2020

Award ID: PTDC/MED-FSL/31719/2017

Award Recipient : Carmen Brás-Silva

Funded by: NETDIAMOND

Award ID: POCI-01-0145-FEDER-016385

Award Recipient : Carmen Brás-Silva

Funded by: DOCnet

Award ID: NORTE-01-0145-FEDER-000003

Award Recipient : Carmen Brás-Silva

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