Application of low-intensity anticoagulation after On-X mechanical aortic valve replacement

Application of low-intensity anticoagulation after On-X mechanical aortic valve replacement | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Application of low-intensity anticoagulation after On-X mechanical aortic valve replacement Kun Zou, Dachuang Wei, Bo Xiang, Tao Yu, Keli Huang, Shengzhong Liu This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4772451/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 09 Jan, 2025 Read the published version in Journal of Cardiothoracic Surgery → Version 1 posted 21 You are reading this latest preprint version Abstract Objective To explore the safety and efficacy of low-intensity anticoagulation in patients after On-X mechanical aortic valve replacement. Methods This study retrospectively collected data from patients diagnosed with aortic valve disease (stenosis or closed insufficiency) who underwent surgical On-X mechanical aortic valve replacement in the Cardiac Surgery Department of Sichuan Provincial People's Hospital from December 2018 to December 2021; the patients were divided into low intensity anticoagulation group (INR:1.5-2.0) and higher intensity anticoagulation group (INR:2.0-2.5) based on postoperative stable INR value (relatively stable INR for 3 months) to compare the incidence of postoperative anticoagulant-related adverse events in the two groups. Results Fifty-three patients were included in the low-intensity anticoagulation group (INR 1.5-2.0), and 51 patients were included in the higher-intensity group (2.0-2.5) in the baseline data and surgery (P > 0.05); the two groups were statistically significant in PT, INR and bleeding events (P 0.05). Conclusion For patients requiring On-X mechanical aortic valve replacement who have no risk factors for thromboembolism, it is appropriate to control the INR in the target range 1.5-2.0, which can reduce the incidence of bleeding adverse events and significantly improve the quality of life, without increasing the risk of thromboembolic adverse events. low-strength anticoagulation warfarin complications On-X mechanical valve aortic valve replacement Background With the increased aging of populations, heart valve disease incidence also increases and seriously endangers human life and health. Valve replacement surgery is an effective means for the treatment of advanced heart valve disease [ 1 – 2 ]. Although the biological valve is favored for short-term anticoagulation, its structural valve deterioration occurs relatively early. In China, rheumatic disease is the main etiology of aortic valve disease; as the age of onset is generally lower than that of other regions, a mechanical valve is still the first choice for aortic valve replacement for most Chinese [ 3 ]. However, the inconvenience and risks of long-term anticoagulation after mechanical valve replacement are distressing[ 4 ]. Surgeons have long pursued low-intensity anticoagulation, seeking a balance between bleeding and embolization events. The On-X valve as a new generation of bi-leaflet mechanical valve which has been demonstrated in Western populations to be safe and effective on low-intensity anticoagulation[ 5 ]. On this basis, we plan to further explore the range of low-intensity anticoagulation after On-X mechanical aortic valve replacement in a Chinese population, and expect to reduce the pain caused by long-term high-intensity anticoagulation in patients going forward. Data and methods 1.5 Case selection: Patients diagnosed with aortic valve disease (stenosis or insufficiency) between December 2018 and December 2018 and December 2021 were selected for the inclusion.. Approval for this trial was obtained from the medical ethics committee of this hospital. Inclusion criteria: ① The age range of patients was 18 to 70 years; ② the follow-up period of surgery and postoperative review was December 2018 to December 2022; ③ patients and family members signed informed consent; ④ surgery was completed by the medical group with experience in cardiac surgery in our hospital; ⑤ patients had high compliance, able to follow the medical advice and return to hospital for review; ⑥ patients had no contraindications of warfarin use. Exclusion criteria: ① chronic atrial fibrillation; ② left ventricular ejection fraction <30%; ③ previous thromboembolic (peripheral and neuroembolic events); ④ hypercoagulable blood; ⑤ with pregnancy and thyroid dysfunction; ⑥ with liver and kidney failure; ⑦ valve replacement except the aortic valve; ⑧ previous history of cardiac surgery; ⑨ acute cardiovascular diseases such as aortic dissection. 1.2 Surgical modality： All patients underwent a median sternal surgical incision, On-X mechanical aortic valve replacement under general anesthesia with hypothermia and cardiopulmonary bypass, and a final evaluation of the artificial mechanical valve using transesophageal echocardiography（TEE) before shutdown. 1.3 Anticoagulation method： On the first day after the operation, the patients were returned to the care unit with a warfarin dose of 3.75mg, the maintenance dose was 1.25-3.75mg/day, and the INR index was reviewed daily. When patients were transferred to the general ward of our department, the INR index was reviewed every 2-3 days. The oral dose of warfarin was adjusted according to the INR value to meet the anticoagulation standard of our department (INR 1.5-2.5). Patients were monitored closely for adverse events during recovery. During hospitalization and postoperative follow-up, if the INR was too high (> 3.0), medication was ceased and vitamin K1 5mg intravenous treatment administered. If renal function occurred, heparin was used in place of warfarin. The INR was monitored to be within the target range for three consecutive tests before discharge. 1.4 Methods and contents of follow-up visits: Patients received long-term oral warfarin anticoagulation therapy after discharge, and follow-up visits were conducted via telecommunication and on-site outpatient services. Based on demonstrated maintenance of stable INR values, 104 patients were divided into low-intensity anticoagulation (INR 1.5-2.0) and higher intensity anticoagulation (INR 2.0-2.5). Stable INR was defined as a fluctuation of less than 20% of the central INR target range (1.5-2.5) for at least 2 weeks, where the stable INR value is the mean value of that time period. The study took the average of the relatively stable INR for 3 consecutive months after surgery. The participants regularly tested INR following discharge, and the oral dose of warfarin was adjusted according to the results. The postoperative follow-up time was 1 year. The patients were monitored for adverse events related to anticoagulation, and were treated in a timely manner according to the methods of anticoagulation during hospitalization. 1.5 Statistical method: Data were analyzed and processed using the SPSS 26.0 statistical software. Measurement data meeting the normal distribution are represented by independent sample t-test, expressed as mean ± standard deviation (x ± s); and expressed by the median (M) and upper and lower quartiles (P25, P75); counting data are expressed by frequency and percentage (2 test or Fisher exact probability method); P 0.05), see Table 1; no statistical differences in cardiac bypass time, aortic blockade, and intensive care unit stay duration (P> 0.05), shown in Table 2. Table 1 Comparison of baseline data indicators in the two groups Baseline data Low intensity anticoagulation（n=53） Higher intensity anticoagulation（n=51） statistic （c2/t/Z） P value Gender,〔n（%）〕 Male Female 38（72.0） 15（28.0） 37（73.0） 14（27.0） 0.009 0.923 Age, years(SD) 47.38±10.34 44.43±11.82 1.353 0.179 BMI, kg/㎡(SD) 23.84±3.62 23.42±3.23 0.621 0.536 hypertension, n(%) 10（18.9） 10（19.6） 0.009 0.924 Diabetes, n(%) 3（5.7） 2（3.9） － 1.0 coronary disease, n(%) 10（18.9） 9（17.6） 0.026 0.872 pathology, n(%) 0.27 0.954 Straitness 3（5.7） 4（7.8） inadequacy 28（52.8） 26（51） miscibility 22（41.5） 21（41.2） etiology, n(%) 0.79 0.885 retrogression 26（49.0） 24（47.1） infectious 11（20.8） 9（17.6） congenital 13（24.5） 13（25.5） other 3（5.7） 5（9.8） NYHA, n(%) -0.39 0.697 I 0（0.0） 0（0.0） II 14（26.4） 16（31.4） III 32（60.4） 28（54.9） IV 7（13.2） 7（13.7） "-" Represents no relevant data Table 2 Comparison of surgery-related indicators in the two patient groups Surgical data Low intensity anticoagulation（n=53） Higher intensity anticoagulation（n=51） statistic （c2/t） P value Valve size, n(%) 0.487 0.834 19mm 5（9.4） 3（5.8） 21mm 24（45.3） 24（47.1） 23mm 24（45.3） 24（47.1） In vitro circulation time（min） 132.21±48.11 137.18±43.16 -0.554 0.581 Aortic block time（min） 89.47±37.43 94.16±37.07 -0.641 0.523 ICU length of stay（h） 63.00±58.03 62.71±62.27 0.024 0.981 2.2 Blood examination and anticoagulation-related adverse events: There was no statistical difference between the prothrombin time PT and the anticoagulant intensity INR (P> 0.05), and the incidence of embolic adverse events in the lower intensity and the group (P> 0.05), but the incidence of bleeding adverse events was significantly lower than that of the group (P <0.05), which were mainly small bleeding events, as shown in Table 3. Table 3 Comparison of anticoagulation-related adverse events during the follow-up period and coagulation function in the first postoperative trimester Anticoagulation-related adverse events Low intensity anticoagulation（n=53） Higher intensity anticoagulation（n=51） statistic （c2/Z） P value prothrombin time, PT（S） 18.5（17.5~19.45） 23.5（22.5~24.8） -8.721 <0.001 Anticoagulation strength, INR(SD) 1.7（1.63~1.77） 2.18（2.11~2.25） -8.79 <0.001 Hemorrhage adverse events, n(%) 6（11.3） 15（39.3） 5.278 0.022 Major bleeding event, n(%) 0（0.0） 1（2.0） － 0.49 Cranial cerebral hemorrhage 0（0.0） 1（2.0） － 0.49 hemorrhage of digestive tract 0（0.0） 0（0.0） － － Small bleeding event, n(%) 6（11.3） 14（27.5） 4.354 0.037 Eye conjunctival haemorrhage 2（3.8） 2（3.9） － 1.0 gingival bleeding 2（3.8） 5（9.8） － 0.265 Subcutaneous congestion and stasis 0（0.0） 1（2.0） － 0.49 hemorrhinia 1（1.9） 4（7.8） － 0.201 Increased menstrual volume 1（1.9） 2（3.9） － 0.614 Adverse embolization events, n(%) 0（0.0） 1（2.0） － 0.49 Postoperative cerebral infarction 0（0.0） 1（2.0） － 0.49 Peripheral arterial embolization 0（0.0） 0（0.0） － － "-" Represents no relevant data Discussion Although aortic valve disease including aortic stenosis and insufficiency may be present without any obvious signs and symptoms at the onset, with the progression of the disease, severe cases can lead to heart failure, secondary valve disease, and even sudden death. The incidence increases with age; the age range 50–59 years old has incidence of about 0.2%, 2.8% in those over 75 years, and 80–90 years old and elderly incidence is up to 9.8% [ 6 ]. Although asymptomatic aortic stenosis or incomplete closure does not increase mortality, mortality has been observed to be up to 50% after 2 years from the onset of symptoms [ 7 ]. 2020 ACC / AHA guidelines state that for patients with severe stenosis or incomplete aortic valve and exertional dyspnea, heart failure, and syncope, Aortic Valve Replacement (AVR) is indicated as the only effective treatment [ 8 ]. In the past, Surgical Aortic Valve Replacement (SAVR) was the only treatment modality, but with the maturity and popularization of catheter interventional technology, Transcatheter Aortic Valve Replacement (TAVR) trends are increasing gradually. However, due to the younger incidence of aortic valve disease in Chinese people and familial socioeconomic factors, SAVR remains the most utilized treatment regimen in China [ 9 – 10 ]. After biological valve replacement, only half a year of conventional anticoagulation is necessary. Therefore, more and more biological valves are implanted globally to avoid the inconvenience and risk caused by long-term anticoagulation. However, structural valve deterioration of biological valves occurs early and advances rapidly, resulting in a higher lifetime reoperation risk [ 11 – 12 ]. Patient age is also an important consideration for valve selection; usually patients with aortic valve disease who are under 60 years of age and without thromboembolism risk factors, and patients with mitral valve disease under 65 years of age are recommended for mechanical valves [ 13 ]. In China, patients with aortic valve disease present at younger ages than those abroad, and often with rheumatic etiology. Therefore, the use of mechanical valves in China is higher than that of biological valves. Since 1951, the artificial mechanical valve has advanced through four designs: ball cage, cage disc, oblique lobe and double lobe or bi-leaflet valve design, progressively becoming more consistent with human cardiac hemodynamics, to relieve patient symptoms and extend life [ 14 ]. The On-X valve is the latest generation of bi-leaflet mechanical valves, incorporating improvements on material and design to reduce the risk of thrombosis, which was first implanted in patients in 1996., Since then several studies have evaluated its safety and efficacy in both the aortic and mitral valve positions [ 5 ], and the thrombogenicity of the On-X valves has been shown to be greatly reduced compared to other mechanical valves [ 15 ]. Since the advent of the mechanical valve, developed regions including Europe and the United States have determined anticoagulation standards through long-term follow-up studies. The American Association of Thoracic Surgeons (AATS) has periodically adjusted the recommended range of anticoagulation INR after mechanical valve replacement, decreasing from 3.0–4.5 in 1989 to 2.5–3.5 in 1992[ 16 ]. The 2020 ACC / AHA guidelines clearly state [ 8 ]: For patients undergoing modern artificial aortic valve therapy without thromboembolic risk factors (atrial fibrillation, previous thromboembolism, left ventricular dysfunction, blood hypercoagulability), the INR target range of 2.0–3.0 can balance the risk of thromboembolism and bleeding, otherwise the INR target should be maintained at 2.5–3.5, and the recommended INR after mitral valve replacement is 3.0. For On-X AVR with no thromboembolic risk factors, it is reasonable to manage anticoagulation in the lower range (1.5-2.0) plus daily low-dose aspirin starting at least 3 months postoperatively, otherwise higher INR (2.5–3.5) should be maintained in the presences of higher risk of thromboembolism [ 17 ]. Due to the late start and slow development of China's medical technology (especially cardiac surgery), China has not formulated a unified anticoagulation standard. Considering the differences between Eastern and Western lifestyles, anticoagulation standards of developed countries in Europe and North America are not suitable for China's national conditions. Given that the risk of bleeding and thromboembolic adverse events is not higher than that of foreign countries, it is likely reasonable to adopt low-intensity anticoagulation standard for On-X AVR in China. In this study, our results showed that among 53 patients in the low-intensity anticoagulation group, 6 patients had bleeding adverse events and none suffered from thromboembolic events; among 51 patients with higher intensity anticoagulation, 15 patients had bleeding events and 1 patient had a cerebral infarction event. The statistical analysis revealed significant differences in the rate of bleeding adverse events (P 0.05). The incidence of adverse events of anticoagulant bleeding in Chinese people is 0.7% -10.4%, and the rate of thromboembolism is 0.3% -1.48%. The former is significantly higher than the latter. The most common adverse event in anticoagulation therapy is bleeding, and the use of low-intensity anticoagulation to reduce bleeding in On-X AVR patients is the key [ 18 ]. Limitations The shortcomings of this study include that the sample size is small and the follow-up period is short. Besides, this study does not include patients with high risk of thromboembolism, and such patients are not applicable for low-intensity anticoagulation. In subsequent research the sample size and follow-up time should be expanded, involving a broader Chinese study population, which would allow further exploration of the risk factors of anticoagulation adverse events and potentially model prediction. Conclusion In conclusion, for patients with On-X mechanical AVR without high risk factors for thromboembolism, the main risk of anticoagulant therapy is propensity for bleeding adverse events. It is feasible to appropriately reduce the anticoagulation intensity to the INR target range of 1.5-2.0, without increasing the risk of thromboembolic adverse events. This can reduce the incidence of bleeding adverse events, while significantly improving patient prognosis and their quality of life. Declarations Conflict of interest None to declare. Funding: This work was supported by the Natural Science Foundation of Sichuan Province, China (Program No.23NSFSC1574), Clinical Translation Research of Sichuan Provincial People’s Hospital(Program No. 2021LY08). Author Contribution Z Drafting the manuscript，D and B acquisition data，Y and H revising the manuscript critically，L Conception and design of study References Otto CM, Prendergast B. Aortic-valve stenosis--from patients at risk tosevere valve obstruction[J]. N Engl J Med. 2014 Aug 21;371(8):744-56. Dobson LE, Prendergast BD. Heart valve disease: a journey of discovery. Heart. 2022;108(10):774-779. Coffey S, Roberts-Thomson R, Brown A, et al. Global epidemiology of valvular heart disease. Nat Rev Cardiol. 2021;18(12):853-864. Sharif Khan H, Ijaz Z, Ali M, et al. Clinical Outcomes of Mechanical Prosthetic Valve Thrombosis. Cureus. 2020;12(6):e8760. Published 2020 Jun 22. Hatoum H, Maureira P, Dasi LP. A turbulence in vitro assessment of On-X and St Jude Medical prostheses[J].J Thorac Cardiovasc Surg. 2019;S0022-5223(19)30484-2. Otto CM, Prendergast B. Aortic-valve stenosis--from patients at risk tosevere valve obstruction[J]. N Engl J Med. 2014 Aug 21;371(8):744-56. Bozso SJ, White A, Kang JJH, et al. Long-term Outcomes Following Mechanical or Bioprosthetic Aortic Valve Replacement in Young Women[J]. CJC Open. 2020 Jun 30;2(6):514-521. Otto CM, Nishimura RA, Bonow RO, et al. 2020 ACC/AHA Guideline for the Management of Patients With Valvular Heart Disease: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines[J].Circulation.2021;143(5):e72-e227. Howard C, Jullian L, Joshi M, et al. TAVI and the future of aortic valve replacement[J]. J Card Surg. 2019;34(12):1577-1590. Mitsis A, Eftychiou C, Eteokleous N, et al.Current Trends in TAVI Access[J]. Curr Probl Cardiol. 2021;46(12):100844. Huckaby LV, Sultan I, Gleason TG, et al. Outcomes of tissue versus mechanical aortic valve replacement in patients 50 to 70 years of age[J]. J Card Surg. 2020 Oct;35(10):2589-2597. Chiang YP, Chikwe J, Moskowitz AJ, et al. Survival and long-term outcomes following bioprosthetic vs mechanical aortic valve replacement in patients aged 50 to 69 years[J]. JAMA. 2014 Oct 1;312(13):1323-9. Iung B，Vahanian A. Epidemiology of acquired valvular heart disease[J]. Can J Cardiol，2014，30（9）：962-970. Manning KB, Deutsch S, Rosenberg G, et al.Tarbell: Artificial Heart and Mechanical Heart Valve Research Contributions[J]. Cardiovasc Eng Technol. 2021;12(1):9-14. Kim JS, Kang Y, Sohn SH, et al.Long-Term Clinical Outcomes of the On-X Mechanical Prosthetic Valve in the Aortic or Mitral Position- A Single-Center Experience of up to 20 Years' Follow up[J]. Circ J. 2021;85(7):1042-1049. Gould MK, Garcia DA, Wren SM, et al. Prevention of VTE in nonorthopedic surgical patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines [J]. Chest. 2012;141(2 Suppl):e227S-e277S. Hatoum H, Maureira P, Dasi LP. A turbulence in vitro assessment of On-X and St Jude Medical prostheses[J].J Thorac Cardiovasc Surg. 2019;S0022-5223(19)30484-2. Cho JG, Lee KH, Kim YR, et al. Standard-Intensity Versus Low-Intensity Anticoagulation with Warfarin in Asian Patients with Atrial Fibrillation: A Multi-Center, Randomized Controlled Trial. Clin Appl Thromb Hemost. 2023;29:10760296231171081. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 09 Jan, 2025 Read the published version in Journal of Cardiothoracic Surgery → Version 1 posted Editorial decision: Revision requested 15 Sep, 2024 Reviews received at journal 08 Sep, 2024 Reviews received at journal 05 Sep, 2024 Reviews received at journal 01 Sep, 2024 Reviews received at journal 28 Aug, 2024 Reviewers agreed at journal 25 Aug, 2024 Reviewers agreed at journal 24 Aug, 2024 Reviews received at journal 24 Aug, 2024 Reviewers agreed at journal 24 Aug, 2024 Reviewers agreed at journal 23 Aug, 2024 Reviewers agreed at journal 23 Aug, 2024 Reviewers agreed at journal 23 Aug, 2024 Reviews received at journal 23 Aug, 2024 Reviewers agreed at journal 23 Aug, 2024 Reviewers agreed at journal 22 Aug, 2024 Reviewers agreed at journal 22 Aug, 2024 Reviewers agreed at journal 22 Aug, 2024 Reviewers invited by journal 22 Aug, 2024 Editor assigned by journal 24 Jul, 2024 Submission checks completed at journal 24 Jul, 2024 First submitted to journal 20 Jul, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4772451","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":334569189,"identity":"f4945204-c5c4-4e21-9729-94cb5a060120","order_by":0,"name":"Kun Zou","email":"","orcid":"","institution":"Mianyang Central Hospital","correspondingAuthor":false,"prefix":"","firstName":"Kun","middleName":"","lastName":"Zou","suffix":""},{"id":334569190,"identity":"1ca2f3fc-237c-4421-a86e-d62cd63cda73","order_by":1,"name":"Dachuang Wei","email":"","orcid":"","institution":"Sichuan Academy of Medical Sciences \u0026 Sichuan Provincial People’s Hospital, Affiliated Hospital of University of Electronic Science and Technology","correspondingAuthor":false,"prefix":"","firstName":"Dachuang","middleName":"","lastName":"Wei","suffix":""},{"id":334569191,"identity":"93d248f6-4fb9-468a-9059-d4534f32846b","order_by":2,"name":"Bo Xiang","email":"","orcid":"","institution":"Sichuan Academy of Medical Sciences \u0026 Sichuan Provincial People’s Hospital, Affiliated Hospital of University of Electronic Science and Technology","correspondingAuthor":false,"prefix":"","firstName":"Bo","middleName":"","lastName":"Xiang","suffix":""},{"id":334569192,"identity":"28f8883a-7f2c-436e-907d-dee415f950ae","order_by":3,"name":"Tao Yu","email":"","orcid":"","institution":"Sichuan Academy of Medical Sciences \u0026 Sichuan Provincial People’s Hospital, Affiliated Hospital of University of Electronic Science and Technology","correspondingAuthor":false,"prefix":"","firstName":"Tao","middleName":"","lastName":"Yu","suffix":""},{"id":334569193,"identity":"12afd115-4a47-492e-840b-cd14030906cc","order_by":4,"name":"Keli Huang","email":"","orcid":"","institution":"Sichuan Academy of Medical Sciences \u0026 Sichuan Provincial People’s Hospital, Affiliated Hospital of University of Electronic Science and Technology","correspondingAuthor":false,"prefix":"","firstName":"Keli","middleName":"","lastName":"Huang","suffix":""},{"id":334569194,"identity":"d169cad0-49fb-4eaa-b1b5-0c760d423dcd","order_by":5,"name":"Shengzhong Liu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAsUlEQVRIiWNgGAWjYBACPmYgwdjAIMfG3n6AOC1sUC3GfDxnEojUwgDRkjhPwsGASC3sPMYf3u44nN4mwZDA8KNiGzEO4zGTnHvmcG6bdOMBxp4zt4nTwszbBtQicyCBmbGNOC3Gn4Fa0tkkEgyI1mIgDdSSQIoWtjLJuW3phm3AQD5IlF/4+Q9v/vC2zVpevr394IMfFURoAQMehmYwfYBI9WAtdcQrHgWjYBSMgpEHAM2FNRJVG4OCAAAAAElFTkSuQmCC","orcid":"","institution":"Sichuan Academy of Medical Sciences \u0026 Sichuan Provincial People’s Hospital, Affiliated Hospital of University of Electronic Science and Technology","correspondingAuthor":true,"prefix":"","firstName":"Shengzhong","middleName":"","lastName":"Liu","suffix":""}],"badges":[],"createdAt":"2024-07-20 09:41:53","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4772451/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4772451/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s13019-024-03215-7","type":"published","date":"2025-01-09T15:57:43+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":73695001,"identity":"578c6759-57b6-4ae5-bd00-4d7da0a15125","added_by":"auto","created_at":"2025-01-13 16:14:32","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":512410,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4772451/v1/b071b181-61d7-4c0d-9b13-8175c95a6696.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Application of low-intensity anticoagulation after On-X mechanical aortic valve replacement","fulltext":[{"header":"Background","content":"\u003cp\u003eWith the increased aging of populations, heart valve disease incidence also increases and seriously endangers human life and health. Valve replacement surgery is an effective means for the treatment of advanced heart valve disease [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e–\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Although the biological valve is favored for short-term anticoagulation, its structural valve deterioration occurs relatively early. In China, rheumatic disease is the main etiology of aortic valve disease; as the age of onset is generally lower than that of other regions, a mechanical valve is still the first choice for aortic valve replacement for most Chinese [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. However, the inconvenience and risks of long-term anticoagulation after mechanical valve replacement are distressing[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Surgeons have long pursued low-intensity anticoagulation, seeking a balance between bleeding and embolization events. The On-X valve as a new generation of bi-leaflet mechanical valve which has been demonstrated in Western populations to be safe and effective on low-intensity anticoagulation[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. On this basis, we plan to further explore the range of low-intensity anticoagulation after On-X mechanical aortic valve replacement in a Chinese population, and expect to reduce the pain caused by long-term high-intensity anticoagulation in patients going forward.\u003c/p\u003e \u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e"},{"header":"Data and methods","content":"\u003cp\u003e\u003cstrong\u003e1.5 Case selection: \u003c/strong\u003ePatients diagnosed with aortic valve disease (stenosis or insufficiency) between December 2018 and December 2018 and December 2021 were selected for the inclusion.. Approval for this trial was obtained from the medical ethics committee of this hospital. Inclusion criteria: ① The age range of patients was 18 to 70 years; ② the follow-up period of \u0026nbsp;surgery and postoperative review was December 2018 to December 2022; ③ patients and family members signed informed consent; ④ surgery was completed by the medical group with experience in cardiac surgery in our hospital; ⑤ patients had high compliance, able to follow the medical advice and return to hospital for review; ⑥ patients had no contraindications of warfarin use. Exclusion criteria: ① chronic atrial fibrillation; ② left ventricular ejection fraction \u0026lt;30%; ③ previous thromboembolic (peripheral and neuroembolic events); ④ hypercoagulable blood; ⑤ with pregnancy and thyroid dysfunction; ⑥ with liver and kidney failure; ⑦ valve replacement except the aortic valve; ⑧ previous history of cardiac surgery; ⑨ acute cardiovascular diseases such as aortic dissection.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e1.2 Surgical modality：\u003c/strong\u003eAll patients underwent a median sternal surgical incision, On-X mechanical aortic valve replacement under general anesthesia with hypothermia and cardiopulmonary bypass, and a final evaluation of the artificial mechanical valve using transesophageal echocardiography（TEE) before shutdown.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e1.3 Anticoagulation method：\u003c/strong\u003eOn the first day after the operation, the patients were returned to the care unit with a warfarin dose of 3.75mg, the maintenance dose was 1.25-3.75mg/day, and the INR index was reviewed daily. When patients were transferred to the general ward of our department, the INR index was reviewed every 2-3 days. The oral dose of warfarin was adjusted according to the INR value to meet the anticoagulation standard of our department (INR 1.5-2.5). Patients were monitored closely for adverse events during recovery. During hospitalization and postoperative follow-up, if the INR was too high (\u0026gt; 3.0), medication was ceased and vitamin K1 5mg intravenous treatment administered. If renal function occurred, heparin was used in place of warfarin. The INR \u0026nbsp;was monitored to be within the target range for three consecutive tests before discharge.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e1.4 Methods and contents of follow-up visits:\u003c/strong\u003e Patients received long-term oral warfarin anticoagulation therapy after discharge, and follow-up visits were conducted via telecommunication and on-site outpatient services. Based on demonstrated maintenance of stable INR values, 104 patients were divided into low-intensity anticoagulation (INR 1.5-2.0) and higher intensity anticoagulation (INR 2.0-2.5). Stable INR was defined as a fluctuation of less than 20% of the central INR target range (1.5-2.5) for at least 2 weeks, where the stable INR value is the mean value of that time period. The study took the average of the relatively stable INR for 3 consecutive months after surgery. The participants regularly tested INR following discharge, and the oral dose of warfarin was adjusted according to the results. The postoperative follow-up time was 1 year. The patients were monitored for adverse events related to anticoagulation, and were treated in a timely manner according to the methods of anticoagulation during hospitalization.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e1.5 Statistical method:\u003c/strong\u003e Data were analyzed and processed using the SPSS 26.0 statistical software. Measurement data meeting the normal distribution are represented by independent sample t-test, expressed as mean \u0026plusmn; standard deviation (x \u0026plusmn; s); and expressed by the median (M) and upper and lower quartiles (P25, P75); counting data are expressed by frequency and percentage (2 test or Fisher exact probability method); P \u0026lt;0.05 is considered statistically significant.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003e2.1\u003c/strong\u003e There were no statistical differences in gender, age, BMI, underlying disease, cardiac function grade, valve etiology, and pathology (P\u0026gt; 0.05), see Table 1; no statistical differences in cardiac bypass time, aortic blockade, and intensive care unit stay duration (P\u0026gt; 0.05), shown in Table 2.\u003c/p\u003e\n\u003cp\u003eTable 1 Comparison of baseline data indicators in the two groups\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"24.958402662229616%\" valign=\"top\"\u003e\n \u003cp\u003eBaseline data\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.96838602329451%\" valign=\"top\"\u003e\n \u003cp\u003eLow intensity anticoagulation（n=53）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.80199667221298%\" valign=\"top\"\u003e\n \u003cp\u003eHigher intensity anticoagulation（n=51）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.302828618968388%\" valign=\"top\"\u003e\n \u003cp\u003estatistic （c2/t/Z）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.96838602329451%\" valign=\"top\"\u003e\n \u003cp\u003eP value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"24.958402662229616%\" valign=\"top\"\u003e\n \u003cp\u003eGender,〔n（%）〕\u003c/p\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.96838602329451%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e38（72.0）\u003c/p\u003e\n \u003cp\u003e15（28.0）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.80199667221298%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e37（73.0）\u003c/p\u003e\n \u003cp\u003e14（27.0）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.302828618968388%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.009\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.96838602329451%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.923\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"24.958402662229616%\" valign=\"top\"\u003e\n \u003cp\u003eAge, years(SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.96838602329451%\" valign=\"top\"\u003e\n \u003cp\u003e47.38\u0026plusmn;10.34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.80199667221298%\" valign=\"top\"\u003e\n \u003cp\u003e44.43\u0026plusmn;11.82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.302828618968388%\" valign=\"top\"\u003e\n \u003cp\u003e1.353\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.96838602329451%\" valign=\"top\"\u003e\n \u003cp\u003e0.179\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"24.958402662229616%\" valign=\"top\"\u003e\n \u003cp\u003eBMI, kg/㎡(SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.96838602329451%\" valign=\"top\"\u003e\n \u003cp\u003e23.84\u0026plusmn;3.62\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.80199667221298%\" valign=\"top\"\u003e\n \u003cp\u003e23.42\u0026plusmn;3.23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.302828618968388%\" valign=\"top\"\u003e\n \u003cp\u003e0.621\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.96838602329451%\" valign=\"top\"\u003e\n \u003cp\u003e0.536\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"24.958402662229616%\" valign=\"top\"\u003e\n \u003cp\u003ehypertension, n(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.96838602329451%\" valign=\"top\"\u003e\n \u003cp\u003e10（18.9）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.80199667221298%\" valign=\"top\"\u003e\n \u003cp\u003e10（19.6）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.302828618968388%\" valign=\"top\"\u003e\n \u003cp\u003e0.009\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.96838602329451%\" valign=\"top\"\u003e\n \u003cp\u003e0.924\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"24.958402662229616%\" valign=\"top\"\u003e\n \u003cp\u003eDiabetes, n(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.96838602329451%\" valign=\"top\"\u003e\n \u003cp\u003e3（5.7）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.80199667221298%\" valign=\"top\"\u003e\n \u003cp\u003e2（3.9）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.302828618968388%\" valign=\"top\"\u003e\n \u003cp\u003e－\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.96838602329451%\" valign=\"top\"\u003e\n \u003cp\u003e1.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"24.958402662229616%\" valign=\"top\"\u003e\n \u003cp\u003ecoronary disease, n(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.96838602329451%\" valign=\"top\"\u003e\n \u003cp\u003e10（18.9）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.80199667221298%\" valign=\"top\"\u003e\n \u003cp\u003e9（17.6）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.302828618968388%\" valign=\"top\"\u003e\n \u003cp\u003e0.026\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.96838602329451%\" valign=\"top\"\u003e\n \u003cp\u003e0.872\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"24.958402662229616%\" valign=\"top\"\u003e\n \u003cp\u003epathology, n(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.96838602329451%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.80199667221298%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.302828618968388%\" rowspan=\"4\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.96838602329451%\" rowspan=\"4\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.954\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"39.787798408488065%\" valign=\"top\"\u003e\n \u003cp\u003eStraitness\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.23872679045093%\" valign=\"top\"\u003e\n \u003cp\u003e3（5.7）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.97347480106101%\" valign=\"top\"\u003e\n \u003cp\u003e4（7.8）\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"39.787798408488065%\" valign=\"top\"\u003e\n \u003cp\u003einadequacy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.23872679045093%\" valign=\"top\"\u003e\n \u003cp\u003e28（52.8）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.97347480106101%\" valign=\"top\"\u003e\n \u003cp\u003e26（51）\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"39.787798408488065%\" valign=\"top\"\u003e\n \u003cp\u003emiscibility\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.23872679045093%\" valign=\"top\"\u003e\n \u003cp\u003e22（41.5）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.97347480106101%\" valign=\"top\"\u003e\n \u003cp\u003e21（41.2）\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"24.958402662229616%\" valign=\"top\"\u003e\n \u003cp\u003eetiology, n(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.96838602329451%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.80199667221298%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.302828618968388%\" rowspan=\"5\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.79\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.96838602329451%\" rowspan=\"5\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.885\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"39.787798408488065%\" valign=\"top\"\u003e\n \u003cp\u003eretrogression\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.23872679045093%\" valign=\"top\"\u003e\n \u003cp\u003e26（49.0）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.97347480106101%\" valign=\"top\"\u003e\n \u003cp\u003e24（47.1）\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"39.787798408488065%\" valign=\"top\"\u003e\n \u003cp\u003einfectious\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.23872679045093%\" valign=\"top\"\u003e\n \u003cp\u003e11（20.8）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.97347480106101%\" valign=\"top\"\u003e\n \u003cp\u003e9（17.6）\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"39.787798408488065%\" valign=\"top\"\u003e\n \u003cp\u003econgenital\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.23872679045093%\" valign=\"top\"\u003e\n \u003cp\u003e13（24.5）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.97347480106101%\" valign=\"top\"\u003e\n \u003cp\u003e13（25.5）\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"39.787798408488065%\" valign=\"top\"\u003e\n \u003cp\u003eother\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.23872679045093%\" valign=\"top\"\u003e\n \u003cp\u003e3（5.7）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.97347480106101%\" valign=\"top\"\u003e\n \u003cp\u003e5（9.8）\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"24.958402662229616%\" valign=\"top\"\u003e\n \u003cp\u003eNYHA, n(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.96838602329451%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.80199667221298%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.302828618968388%\" rowspan=\"5\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e-0.39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.96838602329451%\" rowspan=\"5\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.697\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"39.787798408488065%\" valign=\"top\"\u003e\n \u003cp\u003eI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.23872679045093%\" valign=\"top\"\u003e\n \u003cp\u003e0（0.0）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.97347480106101%\" valign=\"top\"\u003e\n \u003cp\u003e0（0.0）\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"39.787798408488065%\" valign=\"top\"\u003e\n \u003cp\u003eII\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.23872679045093%\" valign=\"top\"\u003e\n \u003cp\u003e14（26.4）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.97347480106101%\" valign=\"top\"\u003e\n \u003cp\u003e16（31.4）\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"39.787798408488065%\" valign=\"top\"\u003e\n \u003cp\u003eIII\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.23872679045093%\" valign=\"top\"\u003e\n \u003cp\u003e32（60.4）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.97347480106101%\" valign=\"top\"\u003e\n \u003cp\u003e28（54.9）\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"39.787798408488065%\" valign=\"top\"\u003e\n \u003cp\u003eIV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.23872679045093%\" valign=\"top\"\u003e\n \u003cp\u003e7（13.2）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.97347480106101%\" valign=\"top\"\u003e\n \u003cp\u003e7（13.7）\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026quot;-\u0026quot; Represents no relevant data\u003c/p\u003e\n\u003cp\u003eTable 2 Comparison of surgery-related indicators in the two patient groups\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.359143327841846%\" valign=\"top\"\u003e\n \u003cp\u003eSurgical data\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.934102141680395%\" valign=\"top\"\u003e\n \u003cp\u003eLow intensity anticoagulation（n=53）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.451400329489292%\" valign=\"top\"\u003e\n \u003cp\u003eHigher intensity anticoagulation（n=51）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.980230642504118%\" valign=\"top\"\u003e\n \u003cp\u003estatistic （c2/t）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.27512355848435%\" valign=\"top\"\u003e\n \u003cp\u003eP value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.359143327841846%\" valign=\"top\"\u003e\n \u003cp\u003eValve size, n(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.934102141680395%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.451400329489292%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.980230642504118%\" rowspan=\"4\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.487\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.27512355848435%\" rowspan=\"4\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.834\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.712468193384225%\" valign=\"top\"\u003e\n \u003cp\u003e19mm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.78880407124682%\" valign=\"top\"\u003e\n \u003cp\u003e5（9.4）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"28.498727735368956%\" valign=\"top\"\u003e\n \u003cp\u003e3（5.8）\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.712468193384225%\" valign=\"top\"\u003e\n \u003cp\u003e21mm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.78880407124682%\" valign=\"top\"\u003e\n \u003cp\u003e24（45.3）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"28.498727735368956%\" valign=\"top\"\u003e\n \u003cp\u003e24（47.1）\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.712468193384225%\" valign=\"top\"\u003e\n \u003cp\u003e23mm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.78880407124682%\" valign=\"top\"\u003e\n \u003cp\u003e24（45.3）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"28.498727735368956%\" valign=\"top\"\u003e\n \u003cp\u003e24（47.1）\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.359143327841846%\" valign=\"top\"\u003e\n \u003cp\u003eIn vitro circulation time（min）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.934102141680395%\" valign=\"top\"\u003e\n \u003cp\u003e132.21\u0026plusmn;48.11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.451400329489292%\" valign=\"top\"\u003e\n \u003cp\u003e137.18\u0026plusmn;43.16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.980230642504118%\" valign=\"top\"\u003e\n \u003cp\u003e-0.554\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.27512355848435%\" valign=\"top\"\u003e\n \u003cp\u003e0.581\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.359143327841846%\" valign=\"top\"\u003e\n \u003cp\u003eAortic block time（min）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.934102141680395%\" valign=\"top\"\u003e\n \u003cp\u003e89.47\u0026plusmn;37.43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.451400329489292%\" valign=\"top\"\u003e\n \u003cp\u003e94.16\u0026plusmn;37.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.980230642504118%\" valign=\"top\"\u003e\n \u003cp\u003e-0.641\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.27512355848435%\" valign=\"top\"\u003e\n \u003cp\u003e0.523\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.359143327841846%\" valign=\"top\"\u003e\n \u003cp\u003eICU length of stay（h）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.934102141680395%\" valign=\"top\"\u003e\n \u003cp\u003e63.00\u0026plusmn;58.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.451400329489292%\" valign=\"top\"\u003e\n \u003cp\u003e62.71\u0026plusmn;62.27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.980230642504118%\" valign=\"top\"\u003e\n \u003cp\u003e0.024\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.27512355848435%\" valign=\"top\"\u003e\n \u003cp\u003e0.981\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003e2.2 Blood examination and anticoagulation-related adverse events:\u003c/strong\u003e There was no statistical difference between the prothrombin time PT and the anticoagulant intensity INR (P\u0026gt; 0.05), and the incidence of embolic adverse events in the lower intensity and the group (P\u0026gt; 0.05), but the incidence of bleeding adverse events was significantly lower than that of the group (P \u0026lt;0.05), which were mainly small bleeding events, as shown in Table 3.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTable 3 Comparison of anticoagulation-related adverse events during the follow-up period and coagulation function in the first postoperative trimester\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"607\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.205930807248766%\" valign=\"top\"\u003e\n \u003cp\u003eAnticoagulation-related adverse events\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.934102141680395%\" valign=\"top\"\u003e\n \u003cp\u003eLow intensity anticoagulation（n=53）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.616144975288304%\" valign=\"top\"\u003e\n \u003cp\u003eHigher intensity anticoagulation（n=51）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.332784184514002%\" valign=\"top\"\u003e\n \u003cp\u003estatistic （c2/Z）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.911037891268535%\" valign=\"top\"\u003e\n \u003cp\u003eP value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.205930807248766%\" valign=\"top\"\u003e\n \u003cp\u003eprothrombin time,\u0026nbsp;PT（S）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.934102141680395%\" valign=\"top\"\u003e\n \u003cp\u003e18.5（17.5~19.45）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.616144975288304%\" valign=\"top\"\u003e\n \u003cp\u003e23.5（22.5~24.8）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.332784184514002%\" valign=\"top\"\u003e\n \u003cp\u003e-8.721\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.911037891268535%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.205930807248766%\" valign=\"top\"\u003e\n \u003cp\u003eAnticoagulation strength,\u0026nbsp;INR(SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.934102141680395%\" valign=\"top\"\u003e\n \u003cp\u003e1.7（1.63~1.77）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.616144975288304%\" valign=\"top\"\u003e\n \u003cp\u003e2.18（2.11~2.25）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.332784184514002%\" valign=\"top\"\u003e\n \u003cp\u003e-8.79\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.911037891268535%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.205930807248766%\" valign=\"top\"\u003e\n \u003cp\u003eHemorrhage adverse events, n(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.934102141680395%\" valign=\"top\"\u003e\n \u003cp\u003e6（11.3）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.616144975288304%\" valign=\"top\"\u003e\n \u003cp\u003e15（39.3）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.332784184514002%\" valign=\"top\"\u003e\n \u003cp\u003e5.278\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.911037891268535%\" valign=\"top\"\u003e\n \u003cp\u003e0.022\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.205930807248766%\" valign=\"top\"\u003e\n \u003cp\u003eMajor bleeding event, n(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.934102141680395%\" valign=\"top\"\u003e\n \u003cp\u003e0（0.0）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.616144975288304%\" valign=\"top\"\u003e\n \u003cp\u003e1（2.0）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.332784184514002%\" valign=\"top\"\u003e\n \u003cp\u003e－\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.911037891268535%\" valign=\"top\"\u003e\n \u003cp\u003e0.49\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.205930807248766%\" valign=\"top\"\u003e\n \u003cp\u003eCranial cerebral hemorrhage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.934102141680395%\" valign=\"top\"\u003e\n \u003cp\u003e0（0.0）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.616144975288304%\" valign=\"top\"\u003e\n \u003cp\u003e1（2.0）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.332784184514002%\" valign=\"top\"\u003e\n \u003cp\u003e－\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.911037891268535%\" valign=\"top\"\u003e\n \u003cp\u003e0.49\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.205930807248766%\" valign=\"top\"\u003e\n \u003cp\u003ehemorrhage of digestive tract\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.934102141680395%\" valign=\"top\"\u003e\n \u003cp\u003e0（0.0）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.616144975288304%\" valign=\"top\"\u003e\n \u003cp\u003e0（0.0）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.332784184514002%\" valign=\"top\"\u003e\n \u003cp\u003e－\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.911037891268535%\" valign=\"top\"\u003e\n \u003cp\u003e－\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.205930807248766%\" valign=\"top\"\u003e\n \u003cp\u003eSmall bleeding event, n(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.934102141680395%\" valign=\"top\"\u003e\n \u003cp\u003e6（11.3）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.616144975288304%\" valign=\"top\"\u003e\n \u003cp\u003e14（27.5）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.332784184514002%\" valign=\"top\"\u003e\n \u003cp\u003e4.354\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.911037891268535%\" valign=\"top\"\u003e\n \u003cp\u003e0.037\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.205930807248766%\" valign=\"top\"\u003e\n \u003cp\u003eEye conjunctival haemorrhage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.934102141680395%\" valign=\"top\"\u003e\n \u003cp\u003e2（3.8）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.616144975288304%\" valign=\"top\"\u003e\n \u003cp\u003e2（3.9）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.332784184514002%\" valign=\"top\"\u003e\n \u003cp\u003e－\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.911037891268535%\" valign=\"top\"\u003e\n \u003cp\u003e1.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.205930807248766%\" valign=\"top\"\u003e\n \u003cp\u003egingival bleeding\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.934102141680395%\" valign=\"top\"\u003e\n \u003cp\u003e2（3.8）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.616144975288304%\" valign=\"top\"\u003e\n \u003cp\u003e5（9.8）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.332784184514002%\" valign=\"top\"\u003e\n \u003cp\u003e－\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.911037891268535%\" valign=\"top\"\u003e\n \u003cp\u003e0.265\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.205930807248766%\" valign=\"top\"\u003e\n \u003cp\u003eSubcutaneous congestion and stasis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.934102141680395%\" valign=\"top\"\u003e\n \u003cp\u003e0（0.0）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.616144975288304%\" valign=\"top\"\u003e\n \u003cp\u003e1（2.0）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.332784184514002%\" valign=\"top\"\u003e\n \u003cp\u003e－\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.911037891268535%\" valign=\"top\"\u003e\n \u003cp\u003e0.49\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.205930807248766%\" valign=\"top\"\u003e\n \u003cp\u003ehemorrhinia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.934102141680395%\" valign=\"top\"\u003e\n \u003cp\u003e1（1.9）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.616144975288304%\" valign=\"top\"\u003e\n \u003cp\u003e4（7.8）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.332784184514002%\" valign=\"top\"\u003e\n \u003cp\u003e－\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.911037891268535%\" valign=\"top\"\u003e\n \u003cp\u003e0.201\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.205930807248766%\" valign=\"top\"\u003e\n \u003cp\u003eIncreased menstrual volume\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.934102141680395%\" valign=\"top\"\u003e\n \u003cp\u003e1（1.9）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.616144975288304%\" valign=\"top\"\u003e\n \u003cp\u003e2（3.9）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.332784184514002%\" valign=\"top\"\u003e\n \u003cp\u003e－\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.911037891268535%\" valign=\"top\"\u003e\n \u003cp\u003e0.614\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.205930807248766%\" valign=\"top\"\u003e\n \u003cp\u003eAdverse embolization events, n(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.934102141680395%\" valign=\"top\"\u003e\n \u003cp\u003e0（0.0）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.616144975288304%\" valign=\"top\"\u003e\n \u003cp\u003e1（2.0）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.332784184514002%\" valign=\"top\"\u003e\n \u003cp\u003e－\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.911037891268535%\" valign=\"top\"\u003e\n \u003cp\u003e0.49\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.205930807248766%\" valign=\"top\"\u003e\n \u003cp\u003ePostoperative cerebral infarction\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.934102141680395%\" valign=\"top\"\u003e\n \u003cp\u003e0（0.0）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.616144975288304%\" valign=\"top\"\u003e\n \u003cp\u003e1（2.0）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.332784184514002%\" valign=\"top\"\u003e\n \u003cp\u003e－\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.911037891268535%\" valign=\"top\"\u003e\n \u003cp\u003e0.49\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.205930807248766%\" valign=\"top\"\u003e\n \u003cp\u003ePeripheral arterial embolization\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.934102141680395%\" valign=\"top\"\u003e\n \u003cp\u003e0（0.0）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.616144975288304%\" valign=\"top\"\u003e\n \u003cp\u003e0（0.0）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.332784184514002%\" valign=\"top\"\u003e\n \u003cp\u003e－\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.911037891268535%\" valign=\"top\"\u003e\n \u003cp\u003e－\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026quot;-\u0026quot; Represents no relevant data\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eAlthough aortic valve disease including aortic stenosis and insufficiency may be present without any obvious signs and symptoms at the onset, with the progression of the disease, severe cases can lead to heart failure, secondary valve disease, and even sudden death. The incidence increases with age; the age range 50\u0026ndash;59 years old has incidence of about 0.2%, 2.8% in those over 75 years, and 80\u0026ndash;90 years old and elderly incidence is up to 9.8% [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Although asymptomatic aortic stenosis or incomplete closure does not increase mortality, mortality has been observed to be up to 50% after 2 years from the onset of symptoms [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. 2020 ACC / AHA guidelines state that for patients with severe stenosis or incomplete aortic valve and exertional dyspnea, heart failure, and syncope, Aortic Valve Replacement (AVR) is indicated as the only effective treatment [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. In the past, Surgical Aortic Valve Replacement (SAVR) was the only treatment modality, but with the maturity and popularization of catheter interventional technology, Transcatheter Aortic Valve Replacement (TAVR) trends are increasing gradually. However, due to the younger incidence of aortic valve disease in Chinese people and familial socioeconomic factors, SAVR remains the most utilized treatment regimen in China [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAfter biological valve replacement, only half a year of conventional anticoagulation is necessary. Therefore, more and more biological valves are implanted globally to avoid the inconvenience and risk caused by long-term anticoagulation. However, structural valve deterioration of biological valves occurs early and advances rapidly, resulting in a higher lifetime reoperation risk [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Patient age is also an important consideration for valve selection; usually patients with aortic valve disease who are under 60 years of age and without thromboembolism risk factors, and patients with mitral valve disease under 65 years of age are recommended for mechanical valves [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. In China, patients with aortic valve disease present at younger ages than those abroad, and often with rheumatic etiology. Therefore, the use of mechanical valves in China is higher than that of biological valves.\u003c/p\u003e \u003cp\u003eSince 1951, the artificial mechanical valve has advanced through four designs: ball cage, cage disc, oblique lobe and double lobe or bi-leaflet valve design, progressively becoming more consistent with human cardiac hemodynamics, to relieve patient symptoms and extend life [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. The On-X valve is the latest generation of bi-leaflet mechanical valves, incorporating improvements on material and design to reduce the risk of thrombosis, which was first implanted in patients in 1996., Since then several studies have evaluated its safety and efficacy in both the aortic and mitral valve positions [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e], and the thrombogenicity of the On-X valves has been shown to be greatly reduced compared to other mechanical valves [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eSince the advent of the mechanical valve, developed regions including Europe and the United States have determined anticoagulation standards through long-term follow-up studies. The American Association of Thoracic Surgeons (AATS) has periodically adjusted the recommended range of anticoagulation INR after mechanical valve replacement, decreasing from 3.0\u0026ndash;4.5 in 1989 to 2.5\u0026ndash;3.5 in 1992[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. The 2020 ACC / AHA guidelines clearly state [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]: For patients undergoing modern artificial aortic valve therapy without thromboembolic risk factors (atrial fibrillation, previous thromboembolism, left ventricular dysfunction, blood hypercoagulability), the INR target range of 2.0\u0026ndash;3.0 can balance the risk of thromboembolism and bleeding, otherwise the INR target should be maintained at 2.5\u0026ndash;3.5, and the recommended INR after mitral valve replacement is 3.0. For On-X AVR with no thromboembolic risk factors, it is reasonable to manage anticoagulation in the lower range (1.5-2.0) plus daily low-dose aspirin starting at least 3 months postoperatively, otherwise higher INR (2.5\u0026ndash;3.5) should be maintained in the presences of higher risk of thromboembolism [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eDue to the late start and slow development of China's medical technology (especially cardiac surgery), China has not formulated a unified anticoagulation standard. Considering the differences between Eastern and Western lifestyles, anticoagulation standards of developed countries in Europe and North America are not suitable for China's national conditions. Given that the risk of bleeding and thromboembolic adverse events is not higher than that of foreign countries, it is likely reasonable to adopt low-intensity anticoagulation standard for On-X AVR in China. In this study, our results showed that among 53 patients in the low-intensity anticoagulation group, 6 patients had bleeding adverse events and none suffered from thromboembolic events; among 51 patients with higher intensity anticoagulation, 15 patients had bleeding events and 1 patient had a cerebral infarction event. The statistical analysis revealed significant differences in the rate of bleeding adverse events (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05) and no significant difference in thromboembolic adverse events (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05). The incidence of adverse events of anticoagulant bleeding in Chinese people is 0.7% -10.4%, and the rate of thromboembolism is 0.3% -1.48%. The former is significantly higher than the latter. The most common adverse event in anticoagulation therapy is bleeding, and the use of low-intensity anticoagulation to reduce bleeding in On-X AVR patients is the key [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eLimitations\u003c/p\u003e \u003cp\u003eThe shortcomings of this study include that the sample size is small and the follow-up period is short. Besides, this study does not include patients with high risk of thromboembolism, and such patients are not applicable for low-intensity anticoagulation. In subsequent research the sample size and follow-up time should be expanded, involving a broader Chinese study population, which would allow further exploration of the risk factors of anticoagulation adverse events and potentially model prediction.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn conclusion, for patients with On-X mechanical AVR without high risk factors for thromboembolism, the main risk of anticoagulant therapy is propensity for bleeding adverse events. It is feasible to appropriately reduce the anticoagulation intensity to the INR target range of 1.5-2.0, without increasing the risk of thromboembolic adverse events. This can reduce the incidence of bleeding adverse events, while significantly improving patient prognosis and their quality of life.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003ch2\u003eConflict of interest\u003c/h2\u003e \u003cp\u003eNone to declare.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding:\u003c/h2\u003e \u003cp\u003eThis work was supported by the Natural Science Foundation of Sichuan Province, China (Program No.23NSFSC1574), Clinical Translation Research of Sichuan Provincial People\u0026rsquo;s Hospital(Program No. 2021LY08).\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eZ Drafting the manuscript，D and B acquisition data，Y and H revising the manuscript critically，L Conception and design of study\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eOtto CM, Prendergast B. Aortic-valve stenosis--from patients at risk tosevere valve obstruction[J]. N Engl J Med. 2014 Aug 21;371(8):744-56.\u003c/li\u003e\n\u003cli\u003eDobson LE, Prendergast BD. Heart valve disease: a journey of discovery. Heart. 2022;108(10):774-779.\u003c/li\u003e\n\u003cli\u003eCoffey S, Roberts-Thomson R, Brown A, et al. Global epidemiology of valvular heart disease. Nat Rev Cardiol. 2021;18(12):853-864. \u003c/li\u003e\n\u003cli\u003eSharif Khan H, Ijaz Z, Ali M, et al. Clinical Outcomes of Mechanical Prosthetic Valve Thrombosis. Cureus. 2020;12(6):e8760. Published 2020 Jun 22.\u003c/li\u003e\n\u003cli\u003eHatoum H, Maureira P, Dasi LP. A turbulence in vitro assessment of On-X and St Jude Medical prostheses[J].J Thorac Cardiovasc Surg. 2019;S0022-5223(19)30484-2.\u003c/li\u003e\n\u003cli\u003eOtto CM, Prendergast B. Aortic-valve stenosis--from patients at risk tosevere valve obstruction[J]. N Engl J Med. 2014 Aug 21;371(8):744-56.\u003c/li\u003e\n\u003cli\u003eBozso SJ, White A, Kang JJH, et al. Long-term Outcomes Following Mechanical or Bioprosthetic Aortic Valve Replacement in Young Women[J]. CJC Open. 2020 Jun 30;2(6):514-521.\u003c/li\u003e\n\u003cli\u003eOtto CM, Nishimura RA, Bonow RO, et al. 2020 ACC/AHA Guideline for the Management of Patients With Valvular Heart Disease: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines[J].Circulation.2021;143(5):e72-e227.\u003c/li\u003e\n\u003cli\u003eHoward C, Jullian L, Joshi M, et al. TAVI and the future of aortic valve replacement[J]. J Card Surg. 2019;34(12):1577-1590.\u003c/li\u003e\n\u003cli\u003eMitsis A, Eftychiou C, Eteokleous N, et al.Current Trends in TAVI Access[J]. Curr Probl Cardiol. 2021;46(12):100844.\u003c/li\u003e\n\u003cli\u003eHuckaby LV, Sultan I, Gleason TG, et al. Outcomes of tissue versus mechanical aortic valve replacement in patients 50 to 70 years of age[J]. J Card Surg. 2020 Oct;35(10):2589-2597.\u003c/li\u003e\n\u003cli\u003eChiang YP, Chikwe J, Moskowitz AJ, et al. Survival and long-term outcomes following bioprosthetic vs mechanical aortic valve replacement in patients aged 50 to 69 years[J]. JAMA. 2014 Oct 1;312(13):1323-9.\u003c/li\u003e\n\u003cli\u003eIung B，Vahanian A. Epidemiology of acquired valvular heart disease[J]. Can J Cardiol，2014，30（9）：962-970.\u003c/li\u003e\n\u003cli\u003eManning KB, Deutsch S, Rosenberg G, et al.Tarbell: Artificial Heart and Mechanical Heart Valve Research Contributions[J]. Cardiovasc Eng Technol. 2021;12(1):9-14.\u003c/li\u003e\n\u003cli\u003eKim JS, Kang Y, Sohn SH, et al.Long-Term Clinical Outcomes of the On-X Mechanical Prosthetic Valve in the Aortic or Mitral Position- A Single-Center Experience of up to 20 Years\u0026apos; Follow up[J]. Circ J. 2021;85(7):1042-1049.\u003c/li\u003e\n\u003cli\u003eGould MK, Garcia DA, Wren SM, et al. Prevention of VTE in nonorthopedic surgical patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines [J]. Chest. 2012;141(2 Suppl):e227S-e277S.\u003c/li\u003e\n\u003cli\u003eHatoum H, Maureira P, Dasi LP. A turbulence in vitro assessment of On-X and St Jude Medical prostheses[J].J Thorac Cardiovasc Surg. 2019;S0022-5223(19)30484-2.\u003c/li\u003e\n\u003cli\u003eCho JG, Lee KH, Kim YR, et al. Standard-Intensity Versus Low-Intensity Anticoagulation with Warfarin in Asian Patients with Atrial Fibrillation: A Multi-Center, Randomized Controlled Trial. Clin Appl Thromb Hemost. 2023;29:10760296231171081. \u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"journal-of-cardiothoracic-surgery","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jcts","sideBox":"Learn more about [Journal of Cardiothoracic Surgery](http://cardiothoracicsurgery.biomedcentral.com)","snPcode":"13019","submissionUrl":"https://submission.nature.com/new-submission/13019/3","title":"Journal of Cardiothoracic Surgery","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"low-strength anticoagulation, warfarin, complications, On-X mechanical valve, aortic valve replacement","lastPublishedDoi":"10.21203/rs.3.rs-4772451/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4772451/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjective\u003c/h2\u003e \u003cp\u003eTo explore the safety and efficacy of low-intensity anticoagulation in patients after On-X mechanical aortic valve replacement.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThis study retrospectively collected data from patients diagnosed with aortic valve disease (stenosis or closed insufficiency) who underwent surgical On-X mechanical aortic valve replacement in the Cardiac Surgery Department of Sichuan Provincial People's Hospital from December 2018 to December 2021; the patients were divided into low intensity anticoagulation group (INR:1.5-2.0) and higher intensity anticoagulation group (INR:2.0-2.5) based on postoperative stable INR value (relatively stable INR for 3 months) to compare the incidence of postoperative anticoagulant-related adverse events in the two groups.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eFifty-three patients were included in the low-intensity anticoagulation group (INR 1.5-2.0), and 51 patients were included in the higher-intensity group (2.0-2.5) in the baseline data and surgery (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05); the two groups were statistically significant in PT, INR and bleeding events (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05), but no significant difference in embolic adverse events (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eFor patients requiring On-X mechanical aortic valve replacement who have no risk factors for thromboembolism, it is appropriate to control the INR in the target range 1.5-2.0, which can reduce the incidence of bleeding adverse events and significantly improve the quality of life, without increasing the risk of thromboembolic adverse events.\u003c/p\u003e","manuscriptTitle":"Application of low-intensity anticoagulation after On-X mechanical aortic valve replacement","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-08-20 09:19:31","doi":"10.21203/rs.3.rs-4772451/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision 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