-->PONE-D-26-05846-->-->Exercise-based cardiac rehabilitation and atherosclerotic plaque regression in ASCVD: is exercise really a game-changer?  A scoping review of controlled trials-->-->PLOS One

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Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #2: Yes

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-->5. Review Comments to the Author

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Reviewer #1: Full title: Is ( capital I) exercise really a game-changer?

Strong points of this paper:

1. Stringent criteria to select researches to answer the relevant question. Out of 425 researches only 5 were selected for analysis.

2. ⁠The mechanism of regression of atherosclerotic plaque from CR is discussed too —- reduction in inflammatory markers.

3. ⁠Synergetic effects of CR and LLTs is emphasised in this paper.

The main limitations of this paper are :

1. Unable to distinguish the role of lipid-lowering therapies in the regression of atherosclerotic plaque (As pointed out by the authors )

2. No hard endpoints and cardiovascular outcomes —- due to short duration follow up

3. ⁠Different CR Regimes, hence unable to identify the effective CR Intervention

4. ⁠The 5 studies analysed in this paper are either open label RCT (four) or non RCT (one)—- many confounding factors.

Nevertheless this paper studies a very important aspect of role of CR which is usually underutilised for secondary cardiovascular diseases prevention. I think it should be used as a hypothesis generating evidence for researchers to do more researches on this issue using RCT—- larger numbers, long term follow up and perhaps hard endpoints study (cardiovascular disease and death) on top of surrogate endpoints ( imaging studies )

Reviewer #2: his scoping review highlights the promising role of exercise-based cardiac rehabilitation (CR) in promoting atherosclerotic plaque regression. By utilizing modalities like HIIT and resistance training alongside standard medical therapy, CR demonstrated significant reductions in plaque volume and improved inflammatory markers across five trials.

However, the review’s conclusions are weakened by critical missing factor of selected studies: the lack of data on statin adherence. Since lipid-lowering therapies are the primary drivers of plaque regression, failing to control for medication compliance makes it difficult to isolate exercise as the definitive "game-changer." Consequently, while CR is an indispensable tool for secondary prevention, large-scale randomized controlled trials are essential to determine if exercise independently drives regression or merely supports pharmacological intervention.

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Reviewer #1: No

Reviewer #2: No

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Exercise-based cardiac rehabilitation and atherosclerotic plaque regression in ASCVD: Is exercise really a game-changer?  A scoping review of controlled trials

PONE-D-26-05846R1

Dear Dr. Dwita Rian Desandri,

Congratulations, your article has been accepted by the academic editor and reviewers.  You now have to meet requirements from the administrative editors, if any.

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.

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Kind regards,

Hean Teik Ong, FRCP, FACC

Academic Editor

PLOS One

Additional Editor Comments (optional):

Congratulations, your article has been accepted by the academic editor and reviewers. You now have to meet requirements from the administrative editors, if any.

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: Yes

Reviewer #2: (No Response)

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

Reviewer #1: Yes

Reviewer #2: (No Response)

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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.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: (No Response)

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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: Yes

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: No further comment All my concerns are addressed.

The paper raised a good point to remind the clinicians the importance of incorporating exercise in the process of helping patients to prevent ASCVD.

Please publish accordingly

Reviewer #2: (No Response)

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Reviewer #1: No

Reviewer #2: No

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