Outcomes and Safety of Direct Oral Anticoagulants (DOACs) versus Vitamin K Antagonists (VKAs) amongst Patients with Valvular Heart Disease (VHD): A Systematic Review and Meta-Analysis
, Beshoy Iskandar 2, Nikhila Chelikam 3, Siddhant Jain 4, Vandit Vyas 5, Tanvi Singla 6, Lavanya Dondapati 7, Ali Bombaywala 8, Appala Suman Peela 9, Milan Khealani 10, Sindhu Mukesh 11, Hariprasad Reddy Korsapati 10, Aishwarya Reddy Korsapati 12, Henok Regassa 13, Nitesh Jain 10, Urvish Patel 3 and Vikramaditya Samala Venkata 14
Round 1
Reviewer 1 Report
The authors investigate an important management issue of DOACs. The systematic review is the best way to better understand this issue. Eight studies involving 14862 patients showed less risk of stroke events and ICB. Introduction is on point but an image is missing. Methods are reasonably described. Results are accordingly described as well as the discussion. Conclusion is missing future prospectives and GL considerations.
Author Response
Dear reviewer thank you for your comment and suggestions.
The conclusion is provided in paragraph 5, Lines 260 to 267. In this study, we describe the composite poor outcome as very low in DOAC vs VKA.
I believe we are missing future prospects here. which I will add as different DOACs need to be studied separately which could answer which one excels in what profile better.
Also, further simultaneous prospective studies between DOAC agents can help stratify better according to their profile of side effects.
I truly appreciate your time.
Author Response File: 
Author Response.docx
Reviewer 2 Report
This is a nice metanalysis, I only suggest to stress the limitation that the use of DOACS in the setting of valvular diseases is non permitted in several country.
I suggest to create a subanalysis dividing the studies in post-hoc analyses of large RCTs and observational studies
Author Response
Dear Reviewer, I appreciate your time providing feedback.
I like your suggestions for post hoc analysis of RCTs. I would definitely work on it in the future. Please look out for my post hoc analysis.
Thank you.
Author Response File: Author Response.docx
Reviewer 3 Report
In the paper “ Outcomes and safety of Direct oral anticoagulants (DOAC) ver-2 sus Vitamin K antagonists (VKA) amongst patients with Valvular heart disease (VHD). A Systematic review and Meta-analysis” Patel et al performed a meatanalysis with the aim to compare VKA and NOAC in AF patients with valvular diseases.
The authors state that they include all studies during the last 10 years. It ends up with eight trails; sub-studies from the four large AF studies comparing NOAC and VKA , the RIVER trial and three small studies where one only include 27 patients.
The topic is of interest but there are some major concern with the present trial.
The two large randomized trials (ENVISAGE and ATLANTIS N Engl J Med. 2021 Dec 2;385(23):2150-2160 ENVISAGE.European Heart Journal, Volume 43, Issue 29, 1 August 2022, Pages 2783–2797) comparing NOAC and VKA in AF patients after TAVI are not included in the analysis.
The authors state that they include mild stenotic left sided valvular diseases as well as biological prosthesis. However in the included AF trials the majority of the patients had regurgitation valvular disease most in the mitral valve. There is questionable if you can mix native valvular disease with biological valves after severe valvular diseases, as well as mitral stenosis and regurgitation and state that the findings can be applied on all VHD.
The authors describe oral anticoagulant treatment with different abbreviations in the manuscript mixing OAC, NOAC and DOAC in different sections.
Author Response
Dear Reviewer thank you for your comment and feedback.
The studies you referring are published after our preliminary analysis. We had our analysis back in September 2021.
I appreciate your time.
Thank you.
Author Response File: Author Response.docx
Round 2
Reviewer 3 Report
No changes have been done according to the previous comments and suggestions. No discussion of why no changes have been made.
The topic is of interest but the conclusion drawn in the manuscript is highly limited since the randomized trials published in the recent years are not included.
Author Response
Dear Editor,
As I explained previously, it is impractical to add any new available studies to this paper. The studies were added until the time of analysis. I am not even sure if there new studies available to add on this article. Adding single new study would be complete new analysis. I hope you understand my point, I am trying to make here. Thank you for your patience.
Ghanshyam
