PONE-D-25-02108HEArt failure Treatment patterns: A pharmacoepidemiological descriptive study in COlombia (the HEATCO study)PLOS ONE

Dear Dr. Machado Alba,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

The study's strengths include its large sample size and detailed design, but concerns about population representation and LVEF classification suggest a need for reevaluation of conclusions and inclusion of broader Latin American data comparisons.

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3.  Thank you for stating the following in the Competing Interests section: [Manuel Machado-Duque have a contractual relationship with Audifarma SA and Institución Universitaria Visión de las Américas.  Andres Gaviria-Mendoza have a contractual relationship with Audifarma SA and Institución Universitaria Visión de las Américas. Luis Valladales-Restrepo have a contractual relationship with Audifarma SA and Institución Universitaria Visión de las Américas. Juan-Sebastian Franco are full-time employee of Bayer Colombia. Maria del Rosario Forero are full-time employee of Bayer Colombia. David Vizcaya are full-time employee of Bayer Hispania (Spain). Marcela Rivera are full-time employee of Bayer Hispania (Spain). Jorge Machado-Alba have a contractual relationship with Universidad Tecnológica de Pereira and Audifarma SA.].

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Reviewers' comments:

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Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Partly

Reviewer #2: Yes

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: No

Reviewer #2: Yes

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3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

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4. Is the manuscript presented in an intelligible fashion and written in standard English?

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Reviewer #1: Yes

Reviewer #2: Yes

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Dr Machado Alba et al present a interesting manuscript that evaluated the prescription patterns of medications for heart failure in a cohort of 4742 patients from Colombia, in a a retrospective

study based on the clinical records of patients. The main findings were: high use of betablockers, RAAS inhibitors and MRAs, intermediate prescription of ARNI y low use of SGLT2 inhibitors, triple therapy with RAASis+β-blockers+MRAs in 58.1% of patients with reduced LVEF and 25.2% with preserved LVEF, while quadruple therapy was used in less than 5%. Authors concluded that subjects with HF and preserved LVEF were treated closer to the recommendations of clinical practice guidelines, while the proportion of indicated therapies according to guidelines recommendations is lower among those with reduced LVEF.

Among the strengths of the study are the fact of presenting real-world information about drugs prescription, the huge sample size, and a very comprehensive design of the protocol. However, there are some comments to evaluate before to being accepted.

Abstract:

1. Authors should provide in this section data about classification of HF according with LVEF, because the definition used in the study (reduced or preserved) is different from the currently accepted (see comment below). In addition, the proportion of patients without LVEF available must be described here.

2. The conclusion “The treatment that patients with heart failure with preserved LVEF receive is closer to the recommendations of clinical practice guidelines” is confused and probably misinterpreted. First, the recommendations of treatment for HFpEF in 2020 were only diuretics and treating comorbidities. Second, current recommendation are SGLT2i and diuretics, with lower level of evidence MRA, ARB and ARNI. Moreover, in this study the proportion of combination therapy was higher in HFrEF. So, this conclusion should be reconsidered

Material and methods

3. One concern is the population included in this study. Age of 68.2 years, no data about LVEF in 30.7% (n=1459), 6,7% in stage B, 54.8% en FC I, only 16% of cardiomyopathies (19% in LVEF below 40), 58.7% of those with LVEF measurements with values above 40%, 5.8% of hospitalizations, and only 6.4% treated by cardiologist suggest that it was at least low risk population, and some patients could be misclassified as HF. This patient profile might be associated with the treatment, since the evidence in patients in stage B or in FC I is different from those in Stage C and FC II and higher. These limitations must be discussed in limitations sections.

4. A major concern is the classification by LVEF. According with Universal definition of HF and all major guidelines, preserved HF is defined by an value ≥50%, and values 41-49 is considered HF with mildly reduced EF (HFmrEF). Treatment recommendation vary between these 2 groups. I suggest reclassified by EF in HFrEF, HFmrEF and HFpEF, presenting in the table the statistical comparison among 3 groups in drug prescription.

Discussion

5. It is important compare the study results not only with European or NorthAmerican cohorts, but with LatinAmerican data, from different countries as well as with AMERICCAASS Registry (Clin Cardiol. 2024 Feb;47(2):e24182. doi: 10.1002/clc.24182. Epub 2023 Nov 30) and global registries that include data from LA (REPORT-HF and INTER-CHF)

6. Again, the conclusion “The treatment that patients with heart failure with preserved LVEF receive is closer to the recommendations of clinical practice guidelines” is confused and probably misinterpreted. First, the recommendations of treatment for HFpEF in 2020 were only diuretics and treating comorbidities. Second, current recommendation are SGLT2i and diuretics, with lower level of evidence MRA, ARB and ARNI. Moreover, in this study the proportion of combination therapy was higher in HFrEF. So, this conclusion should be reconsidered

Reviewer #2: The authors retrospectively examine the prescription patterns of medications for the treatment of heart failure in a cohort of patients from Colombia between 2019 and 2020. Patients were classified according to functional class, stage, and left ventricular ejection fraction (LVEF). A total of 4742 patients were evaluated, with a mean age of 68.2±13.8 years and a male predominance (61.3%). A total of 92.0% were classified as stage C and 54.8% as functional class I, the mean LVEF was 42.9±14.8%, and 28.5% had reduced LVEF. The most common causes were ischemic heart disease (44.0%) and arterial hypertension (29.7%). A total of 5.2% had hospitalizations for heart failure in the last year, and 75.6% were attended by a general practitioner. These patients were treated with β-blockers (88.3%), renin-angiotensin-aldosterone system inhibitors (RAASis) (83.1%), loop diuretics (46.8%), and mineralocorticoid receptor antagonists (MRAs) (46.5%). Triple therapy with RAASis+β-blockers+MRAs was received by 58.1% of patients with reduced LVEF and 25.2% with preserved LVEF, while quadruple therapy adding a sodium-glucose cotransporter-2 inhibitor (SGLT2i) was given to 4.9% and 1.4%, respectively.

The review is interesting, but the mean problem is the lack of consideration of the condition of frailty which represents one of the most frequent conditions affecting patients with heart failure.

Please consider and discuss:

Testa G, Curcio F, Liguori I, Basile C, Papillo M, Tocchetti CG, Galizia G, Della-Morte D, Gargiulo G, Cacciatore F, Bonaduce D, Abete P. Physical vs. multidimensional frailty in older adults with and without heart failure. ESC Heart Fail. 2020 Jun;7(3):1371-1380.

Cacciatore F, Amarelli C, Maiello C, Pratillo M, Tosini P, Mattucci I, Salerno G, Curcio F, Elia F, Mercurio V, Golino P, Bonaduce D, Abete P. Effect of Sacubitril-Valsartan in reducing depression in patients with advanced heart failure. J Affect Disord. 2020 Jul 1;272:132-137.

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Reviewer #1: Yes:  Eduardo R Perna, MD

Reviewer #2: No

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HEArt failure Treatment patterns: A pharmacoepidemiological descriptive study in COlombia (the HEATCO study)

PONE-D-25-02108R1

Dear Dr. Jorge Enrique Machado Alba ,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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Kind regards,

Francesco Curcio, M.D., Ph.D.

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

In accordance with the reviewers’ recommendations, we are pleased to accept the manuscript.

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

Reviewer #2: (No Response)

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2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: (No Response)

Reviewer #2: Yes

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3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: (No Response)

Reviewer #2: Yes

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4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: (No Response)

Reviewer #2: Yes

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5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: (No Response)

Reviewer #2: (No Response)

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6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: This manuscript was previously reviewed and has been revised. The revised paper and the response of the Authors to the prior reviews were examined. The paper was summarized in my earlier review. The comments offered in my initial review have been addressed in a satisfactory manner by the authors. There was a useful modification of the manuscript and I recommend accepting it

Reviewer #2: No further comments. The manuscript is really improved, all questions are solved and the manuscript merits to be published.

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7. PLOS authors have the option to publish the peer review history of their article (what does this mean? ). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy .

Reviewer #1: No

Reviewer #2: No

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