Non-Vitamin K Antagonist Oral Anticoagulants and Risk of Myocardial Infarction in Patients with Atrial Fibrillation with or without Percutaneous Coronary Interventions: A Meta-Analysis

Round 1

Reviewer 1 Report

Authors prepared the meta-analysis assessing the risk of MI and MACE during NOAC therapy compared to VKA in patients with AF, both treated and not treated with PCI. Authors presented the thorough literature search and proper/convincing justification of included and excluded studies. The results are quite interesting and vital for therapy individualization, especially in pts undergoing PCI.

 

I have a few minor comments:

1. I would suggest to decrease the number of used abbreviations. 
2. In the Methods section authors should clearly define the „on-treatment” group/analysis, and how it differed from ITT group/analysis.
3. It would be beneficial (especially for general audiance) if authors could add a few sentences of explanations how SUCRA works. It could be added to the supplementary file (not necessary to the main text).

Author Response

"Please see the attachment."

Author Response File: Author Response.docx

Reviewer 2 Report

The Authors performed systematic review to evaluate the risk of MI and major adverse cardiac events during NOAC therapy compared to VKA in patients with AF, both treated and not treated with percutaneous coronary interventions. The Authors performed a very complex and comprehensive analysis.

 

The Authors extensively describe the statistical approach. However, this reviewer believes that the readability of the manuscript is very low and the main message of the manuscript is lost in a plethora of confirmatory results. A meta-analysis is a powerful statistical instrument to sum up the available evidences and to provide new ones but, in the present form, the manuscript with more than fifty figures and tables is extraordinary misleading.

This reviewer suggest to strongly modify the manuscript and to perform exclusively those few comparisons to add new evidences. A good approach could be to limit the analysis to the network meta-analysis.

Author Response

Thank you very much for your reviews. We are aware that our meta-analysis is extensive, but for the sake of a fair view of the subject, we have made a number of calculations, including the dose of dabigatran. We have left only the most important information in the main text.

A classical meta-analysis was performed to compare drug classes: NOACs vs. warfarin, i.e. DTI and FXa inhibitors. In making these comparisons, our aim was to show differences in the efficacy of certain classes, not individual drugs. In contrast, a network meta-analysis was performed to evaluate both individual drugs and their doses.

Such a large number of figures results from the fact of adding a supplement to the work, where all our calculations and proven assumptions required for meta-analysis are attached. We have added a supplement as proof that we have followed all the steps necessary to perform the meta-analysis. For the sake of clarity of the work, most of the figures and pictures have been included in a supplement file.

For reliable statistical analysis, we also had to perform a double counting for the dabigatran group, once including drug dose and once without drug dose.

At the request of Reviewer 1, we extended the description of the SUCRA method, which was included in the supplement.

If such a will remains, we can possibly transfer Figure 6 to the supplement (applies to the SUCRA analysis).