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PONE-D-19-21413

A systematic review and meta-analysis on the effectiveness of an early invasive strategy compared to a conservative approach in elderly patients with non-ST elevation acute coronary syndrome

PLOS ONE

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1. Thank you for inlcuding your competing interests statement; "I have read the journal's policy and the authors of this manuscript have the following competing interests:

RRC: member of advisory board or speakers’ pool of Servier, Boehringer Ingelheim, Menarini, LRI-Therapharma, Sanofi, UAP Pharma, Unilab; MTR: member of speakers’ pool of Novartis, Servier, Astra Zeneca; the rest declare no conflict of interest."

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Review Comments to the Author

Reviewer #1: The paper is very interesting.

Major issues.

Elderly patients in the title and abstract and the whole paper should be better defined>older than 65 years old is not "elderly". Maybe adding median age should be better

Abstract>in the methods authors state that they used fixed effect, although with high inconstency (i2 90%). Fixed effect should not be used for levels of I2 more than 30%. Please follow cochrane guidelines.

Frailty should be largely discusse, as may deeply impact on management of these patients (quote PMID: 28143778 ).

Lenght of dapt in these patients remains an issue, and should

1) explored with meta. regression analysis

2) discussed (quote on PMID: 30862233)

Reviewer #2: This metanalysis would basically be helpful as it tries to clarify a relevant point about management of NSTE-ACS elderly patients.

The following points limit, however, the conclusions deriving from the analysis.

1. Some more information would be helpful to put the results in the right perspective. Thus, the authors should: a) report the average duration of follow-up for each of the end-points; b) to specify the proportion of patients undergoing by-pass surgery vs. percutaneous coronary intervention; c) the proportion of patients who underwent coronary revascularization during hospital staying in the conservative group.

2. Figure 2 shows that the study by Puymirat et al. achieved results strongly different from the other studies as far as global mortality is concerned. Accordingly, the authors should at least present the results of the metanalysis also after removing this study.

3. Although significantly higher than that of the interventional group, coronary revascularization in the conservative group was rather low (8% vs. 2%), which may not justify a broad application of the invasive strategy to all elderly patients.

A systematic review and meta-analysis on the effectiveness of an invasive strategy compared to a conservative approach in patients > 65 years old with non-ST elevation acute coronary syndrome

PONE-D-19-21413R1

Dear Dr. Reano,

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

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Carmine Pizzi

Academic Editor

PLOS ONE

Reviewer #1: Yes: Fabrizio D'Ascenzo