Bempedoic Acid and Statins in Lipid-Lowering Strategy: Which Came First, the Egg or the Chicken?
, Riccardo Molinari 1,2, Rosa Franzese 1,2, Noemi Mollo 1,2 and Giovanni Cimmino 2,3,*Round 1
Reviewer 1 Report
This review deals with a current topic of real medical interest that highlights the efficacy and safety profile of the bempedoic acid.
Please consider the following suggestions:
1. I would advise the authors to include the eligibility criteria of the articles used in this review.2. Please include a clear aim of the study at the end of the Introduction section.
3. Please include a Conclusions section consistent with the evidence and arguments presented in this manuscript.
Author Response
We thank the reviewer for the time he/she spent to review our article and for the criticisms he/she raised. We felt they were appropriate and the revised version of our manuscript is improved because of that. In meanwhile of the revision of the present manuscript an important trial on the use of bempedoic acid, the CLEAR Outcomes, has been published. Thus, for a complete discussion, we have included the findings of this important trial to the revised version of manuscript.
To facilitate the reader, all changes are in red.
Please consider the following suggestions:
- I would advise the authors to include the eligibility criteria of the articles used in this review.
ANSWER. We thank the reviewer for his/her suggestion. We have added the modality of articles selection in the introduction section (page 2, lines 67-69)
Please include a clear aim of the study at the end of the Introduction section.
ANSWER. We apologize for the missing information. The aim of the present review has been stated as indicated (page 2, line 62-69)
Please include a Conclusions section consistent with the evidence and arguments presented in this manuscript.
ANSWER. We thank the reviewer for his/her suggestion. Conclusions section has been added to Future Perspectives
Reviewer 2 Report
The authors have assembled current and useful data relating to the use of bempedoic acid as LDL-C lowering agent. The data seem to be reported accurately, but in introducing the subject, the authors' stance seems rather biased
1. For example, the abstract contains the statement that this drug should be 'used before statins' - there is no existing guidance to support this statement as far as I am aware. If the authors are stating their viewpoint, or an argument which they wish to put forward to the reader, then it should be clearly identified.
2. Again, in the introduction 'highly effective drugs' are separated from the use of statins - this implies that statins are not highly effective.
3. Some conflicting statements are made on the extent of clinical testing of bempedoic acid - compare line 60 [16] with line 64
4. All comparisons made are with statins, but comparisons with PCSK9 inhibitors are relevant, particularly in terms of efficacy and dose.
5. The authors should eliminate any colloquial terms e.g. 'on top up' (Abstract) and 'the new statin' - these are imprecise and do not aid clarity
Author Response
We thank the reviewer for the time he/she spent to review our article and for the criticisms he/she raised. We felt they were appropriate and the revised version of our manuscript is improved because of that. In meanwhile of the revision of the present manuscript an important trial on the use of bempedoic acid, the CLEAR Outcomes, has been published. Thus, for a complete discussion, we have included the findings of this important trial to the revised version of manuscript.
To facilitate the reader, all changes are in red.
The authors have assembled current and useful data relating to the use of bempedoic acid as LDL-C lowering agent. The data seem to be reported accurately, but in introducing the subject, the authors' stance seems rather biased
- For example, the abstract contains the statement that this drug should be 'used before statins' - there is no existing guidance to support this statement as far as I am aware. If the authors are stating their viewpoint, or an argument which they wish to put forward to the reader, then it should be clearly identified.
ANSWER. We apologize for this misleading statement. The mechanism of action of this new drug might support its use before statin treatment then to better titrate the statin dose. However, we agree with the reviewer that this sentence might be confounding for the readers, thus we have removed the personal belief adding a based-evidence statement of its use in addition to statin with the opportunity to better titrate the statin dose
- Again, in the introduction 'highly effective drugs' are separated from the use of statins - this implies that statins are not highly effective.
ANSWER. We thank the reviewer for his/her suggestion. We have modified the sentence removing the confounding words
- Some conflicting statements are made on the extent of clinical testing of bempedoic acid - compare line 60 [16] with line 64
ANSWER. We thank the reviewer to point it out. We have rephrased the sentence to avoid the conflicting statements
- All comparisons made are with statins, but comparisons with PCSK9 inhibitors are relevant, particularly in terms of efficacy and dose.
ANSWER. We thank the reviewer to point it out. This is a critical issue. However, we have limited our analysis to statin because of their sequential mechanism of action. PCSK9i are another class of lipid lowering drugs with a biochemical pathway that differs from statins and bempedoic acid. We have clearly stated this aim in the introduction section (page 2, lines 62-64)
- The authors should eliminate any colloquial terms e.g. 'on top up' (Abstract) and 'the new statin' - these are imprecise and do not aid clarity
ANSWER. We thank the reviewer for his/her suggestion. We have replaced the terms “on top of” with “in addition to” and removed the term “new statin”
Reviewer 3 Report
Dear Author(s),
Thank you for your interesting review on bempedoic acid. The present review nicely higlights the biochemical and pharmacological characteristics of bempedoic acid, clinical data that support its use in the management of the cardiovascular patients and its allocation in the lipid lowering scenario already enriched in drugs of proven efficacy.
I am very satisfied with the quality of this manuscript and I do not have any further suggestions to disclose.
Best regards, Reviewer
Author Response
We thank the reviewer for his/her kind words.
Round 2
Reviewer 2 Report
The authors have addressed my concerns very effectively, and I recommend publication of this detailed and interesting review
