Title: Should oral anticoagulant therapy be continued during dental extraction? A meta-analysis

Transcription

1 Author s response to reviews Title: Should oral anticoagulant therapy be continued during dental extraction? A meta-analysis Authors: Shuo Yang (sophiasure@163.com) Quan Shi (shiquan3333@sina.cn) Jinglong Liu (summer_mimosa@hotmail.com) Jinru Li ( @qq.com) Juan Xu (newxj@hotmail.com) Version: 1 Date: 21 Jul 2016 Author s response to reviews: Dear Editors: On behalf of my co-authors, we thank you very much for giving us an opportunity to revise our manuscript, we appreciate editor and reviewers very much for their positive and constructive comments and suggestions on our manuscript entitled Should oral anticoagulant therapy be continued during dental extraction? A meta-analysis. (ID: OHEA-D ). We have studied reviewers comments carefully and have made revision which marked in red in the paper. We have tried our best to revise our manuscript according to the comments. We would like to express our great appreciation to you and reviewers for comments on our paper. Looking forward to hearing from you.

2 Thank you and best regards. Yours sincerely, Juan Xu Corresponding author: Name: Juan Xu List of Responses Dear Editors and Reviewers: Thank you for your letter and for the reviewers comments concerning our manuscript entitled Should oral anticoagulant therapy be continued during dental extraction? A meta-analysis (ID: OHEA-D ). Those comments are all valuable and very helpful for revising and improving our paper, as well as the important guiding significance to our researches. We have studied comments carefully and have made correction which we hope meet with approval. Revised portion are marked in red in the paper. The main corrections in the paper and the responds to the reviewers comments are as flowing: Responds to the reviewers comments: Reviewer #1: 1.Response to comment: (why did you exclude antiplatelet medications?) Response: I excluded antiplatelet medications because anticoagulant drugs and antiplatelet drugs are two different drugs. Antiplatelet drugs could prevent platelet aggregation; they affect platelets by two different pathways (inhibition of cyclo-oxygenase I or adenosine diphosphate receptors). However, the anticoagulants mainly influence the coagulation pathways (extrinsic and/or intrinsic). Besides, effect of antiplatelet agents for bleeding after tooth extraction has been studied thoroughly, and meta-analyses have been done. So I mainly studied the anticoagulant drugs.

3 Special thanks to you for your good comment. Reviewer #2: 1.Response to comment: ( Abstract Conclusion "evidence" instead of "evidences") Response: We are very sorry for our incorrect writing. And we have made correction according to the Reviewers comments. 2.Response to comment: (Background : P1L7 add platelet aggregation inhibitors) Response: Thank you very much for your good comment. I want to make an explain about this question. Anticoagulants and antiplatelets are both antithrombotic drugs. And they are two different drugs. The real anticoagulation therapy is, however, the one influencing the coagulation pathways (extrinsic and/or intrinsic) and, therefore, antiplatelets are not properly considered as anticoagulants, although their intake should always be considered in any patient with a risk of bleeding [1, 2]. In this article we mainly talked about patients under oral anticoagulant therapy not antiplatelet therapy. So I didnt add platelet aggregation inhibitors in this sentence. 1. Madrid, Carlos Sanz, Mariano: What influence do anticoagulants have on oral implant therapy? A systematic review, Clinical Oral Implants Research 2009, 20: Kent DM, Dahabreh IJ, Ruthazer R: Anticoagulant vs. antiplatelet therapy in patients with cryptogenic stroke and patent foramen ovale: an individual participant data metaanalysis, Eur Heart J 2015, 36(35): Response to comment: (Background : thromboembolism) P2L5 mention "severe consequence" of Response: We have re-written this part according to the Reviewers suggestion as follows: Though the incidence of thromboembolism is low, the consequence is deadly. These thromboembolic events can have devastating clinical consequences, such as an embolic stroke, which can result in major disability or death, or myocardial ischaemia, which can increase risk of death two to four fold [11]. The revision was marked in red in the paper. (Background P2L6)

4 Reference: 11. Kaplan RC, Tirschwell DL, Longstreth WJ, Manolio TA, Heckbert SR, Lefkowitz D, El- Saed A, Psaty BM: Vascular events, mortality, and preventive therapy following ischemic stroke in the elderly. NEUROLOGY 2005, 65(6): Response to comment: (Methods P2L14 why was antiplatelet medication excluded) Response: As my previous answer, I excluded antiplatelet medications because anticoagulant drugs and antiplatelet drugs are two different drugs. Antiplatelet drugs could prevent platelet aggregation; they affect platelets by two different pathways (inhibition of cyclo-oxygenase I or adenosine diphosphate receptors). However, the anticoagulants mainly influence the coagulation pathways (extrinsic and/or intrinsic). Besides, effect of antiplatelet agents for bleeding after tooth extraction has been studied thoroughly, and meta-analyses have been done. So I mainly studied the anticoagulant drugs. 5.Response to comment: (Results P1L16 did all patients from the anti-vitamin K group receive warfarin or has also "marcumar" or "falithrom" be included, please mention) Response: It is really true as Reviewer concerned that patients from the anti-vitamin K group receive which drugs. I also noticed this question. But the article didnt point out what kind of drugs. 6.Response to comment: (Discussion mentioned in the discussion) P1L11 The aspect of renal dysfunction should be Response: We have added this part according to the Reviewers suggestion as follows: Next to monitoring the INR, it is recommended to take a special care of patients with renal dysfunction. Given the renal excretion of drugs, renal dysfunction may result in a higher incidence of bleeding associated with oral anticoagulation [40, 41]. The revision was marked in red in the paper. (Discussion P3L3) 40. Piccini JP, Stevens SR, Chang Y, Singer DE, Lokhnygina Y, Go AS, Patel MR, Mahaffey KW, Halperin JL, Breithardt G et al: Renal dysfunction as a predictor of stroke and systemic embolism in patients with nonvalvular atrial fibrillation: validation of the

5 R(2)CHADS(2) index in the ROCKET AF (Rivaroxaban Once-daily, oral, direct factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation) and ATRIA (AnTicoagulation and Risk factors In Atrial fibrillation) study cohorts. CIRCULATION 2013, 127(2): Hart RG, Eikelboom JW, Ingram AJ, Herzog CA: Anticoagulants in atrial fibrillation patients with chronic kidney disease. NAT REV NEPHROL 2012, 8(10): Response to comment: (Discussion P2L15 Please mention different indications for vit. K antagonists (atrial fibrillation, deep venous thrombosis,) referring to the different values of INR recommended) Response: We have re-written this part according to the Reviewers suggestion as follows: For stroke prevention in atrial fibrillation patients, oral anticoagulation therapy that is dose adjusted to maintain an INR range of 2.0 to 3.0 is associated with a 64 % reduction in the risk of stroke compared to placebo [32]. And in patients suffering an acute venous thromboembolism (either deep vein thrombosis or pulmonary embolism), adjusted-dose OAT use significantly reduces the risk of recurrence of thrombotic events with a target INR range of [33]. According to meta-analyses of atrial fibrillation or mixed populations assessing INR control and associated events [34], more than half of all thromboembolic events occurred when patients have an INR < 2.0. The revision was marked in red in the paper. (Discussion P2L14) 32. Hart RG, Pearce LA, Aguilar MI: Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation. ANN INTERN MED 2007, 146(12): Kearon C, Akl EA, Ornelas J, Blaivas A, Jimenez D, Bounameaux H, Huisman M, King CS, Morris TA, Sood N et al: Antithrombotic Therapy for VTE Disease: CHEST Guideline and Expert Panel Report. CHEST 2016, 149(2): Erkens PM, Ten CH, Buller HR, Prins MH: Benchmark for time in therapeutic range in venous thromboembolism: a systematic review and meta-analysis. PLOS ONE 2012, 7(9):e We tried our best to improve the manuscript and made some changes in the manuscript. We appreciate for Editors/Reviewers warm work earnestly, and hope that the correction will meet with approval. Once again, thank you very much for your comments and suggestions.