Trends in Emergency Department Anticoagulant Prescription for Patients with Venous Thromboembolism in China, 2016-2019

Trends in Emergency Department Anticoagulant Prescription for Patients with Venous Thromboembolism in China, 2016-2019 | 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 Trends in Emergency Department Anticoagulant Prescription for Patients with Venous Thromboembolism in China, 2016-2019 Xia Wang, Xin Liu, Zhigang Zhao, Wei Guo This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-1878216/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Introduction: Untreated acute venous thromboembolism (VTE) can have catastrophic consequences. Patients should be anticoagulated as soon as VTE is diagnosed. Based on the current clinical guidelines, direct oral anticoagulants (DOACs) are recommended as the first-line anticoagulant treatment for VTE. However, the selection of anticoagulants is a complex task, especially in the emergency department (ED). Methods This population-based drug utilization study was conducted to investigate the status of anticoagulant prescriptions for VTE treated in the ED (ED-VTE; ICD-10 codes I26, I80, I82, and I27.82) and the trend in these prescriptions in four major Chinese cities (Beijing, Tianjin, Shanghai, and Guangzhou) between 2016.1.1 and 2019.12.31. All data were retrieved from a cooperative data program established by the Peking Union Medical College Hospital. Patients who were anticoagulated for initial or recurrent VTE in the EDs of participating institutions during the study period were included in the present analysis. The primary objective was to characterize the trend in anticoagulant prescriptions for ED-VTE; the secondary objective was to calculate the average cost of anticoagulants per prescription. The sample size was not estimated before data collection due to the retrospective nature of the study and the current scarcity of data on anticoagulant prescribing for ED-VTE. Results a total of 4609 prescriptions for anticoagulants were retrieved; none of these records was found to have incomplete data. The anticoagulants prescribed in the current study included low-molecular-weight heparin (LMWH), warfarin, dabigatran, and rivaroxaban. Of the included prescriptions, 63.9% were given to patients over 65 years old, and 55.0% were given to females. The city of Shanghai accounted for nearly half of the prescriptions. Generally, LMWH was the most frequently prescribed anticoagulant in the ED. Warfarin accounted for more than 60% of all oral anticoagulant prescriptions during the study period; the second most prescribed oral anticoagulant was rivaroxaban (32.1%). The utilization of rivaroxaban increased to 48.4% of all oral anticoagulants in 2019. Dabigatran was less frequently prescribed. Conclusion The selection of anticoagulants in the ED was complex. LMWH remained the most prescribed anticoagulant regardless of time, gender, institution location, or cost. Warfarin was the most prescribed oral anticoagulant from 2016 to 2018, but the number of rivaroxaban prescriptions exceeded the number of warfarin prescriptions in 2019. DOACs accounted for an increasing share of anticoagulant prescriptions during the study period. Further investigations are warranted. Venous thromboembolism anticoagulation emergency department China Figures Figure 1 Figure 2 Introduction Venous thromboembolism (VTE), clinically presenting as deep vein thrombosis (DVT) and pulmonary embolism (PE), is a major contributor to the global burden of disease and affects nearly 10 million people worldwide each year. 1 , 2 VTE is commonly diagnosed in the emergency department (ED) and ranks as the third most frequent acute cardiovascular syndrome, behind myocardial infarction and stroke. 2 VTE is a fatal disease. It has been reported that almost 5% of patients die within a week after the diagnosis of PE, and one-fifth of patients who have experienced an index VTE event die within a year. 3 , 4 In consideration of the catastrophic consequence of untreated acute VTE, computed tomography pulmonary angiography (CTPA) and compression ultrasonography are widely utilized to identify suspected VTE patients in the ED, which creates onerous diagnosis and management burdens for ED physicians. Once VTE is diagnosed, patients should be anticoagulated to prevent thrombus extension, embolism, recurrence, death, and other long-term complications. 5 Managements for VTE involve anticoagulation, thrombolysis, vena cava filters, elastic compression, and other supportive therapies, among which anticoagulation remains the cornerstone. Anticoagulation therapy is expected to be maintained for at least 3 to 6 months to minimize the risks for thrombus recurrence. 5 Long-term administration of anticoagulants is weighed as an option by comparing the risk of VTE events to the risk of major bleeding. 6 – 9 Anticoagulants for VTE include unfractionated heparin (UFH), low-molecular-weight heparin (LMWH), vitamin K–dependent antagonists (VKAs, i.e., warfarin), and direct oral anticoagulants (DOACs). Anticoagulation therapy for an acute VTE event includes initial anticoagulation (systemic anticoagulation during the first few days after a VTE diagnosis), long-term anticoagulation (anticoagulation beyond the initial period, usually three to twelve months), and extended anticoagulation (anticoagulation that is administered indefinitely) if needed. The therapeutic effects and safety of the above agents differ depending on patients' conditions and comorbidities. Abundant clinical trials indicate that DOACs and VKAs produce comparable effects on symptomatic VTE, while DOACs are associated with a reduced risk of major bleeding and reduced healthcare demands. 10 , 11 In clinical practice, however, the selection of anticoagulants is complex. 9 It relies on medical considerations and availability, patient comorbidities, preferences, convenience, and financial situations. Vitamin-K antagonists remain the most widely used anticoagulation drug in the ED, although improving evidence suggests that DOACs are more viable and cost effective than conventional anticoagulation among acute VTE patients. 12 , 13 Several studies have been conducted to investigate the prescription of anticoagulants in VTE patients to obtain an extensive understanding of this gap between medical recommendations and clinical practice. 14 , 15 However, little is known concerning the trend in anticoagulant prescription for ED patients with VTE. 12 The current study retrieved all available prescriptions of anticoagulants from the EDs of four major cities in China as representatives. This demographic study aims to investigate the status of anticoagulant prescription for Chinese VTE patients and describe the trend in their use. Methods The current study is a population-based drug utilization study conducted to investigate the status and trend in anticoagulant prescriptions among patients diagnosed with VTE (ICD-10 codes I26, I80, I82, and I27.82) in the ED of four major Chinese cities (Beijing, Tianjin, Shanghai, and Guangzhou) between 2016 and 2019. All data were retrieved from a corporative data program constructed by the Peking Union Medical College Hospital, compromising more than 100 hospitals in thirty-five Chinese cities. The pharmacy prescriptions were recorded in bins of ten consecutive days. The included medical institutions covered more than 500 million patients and were located in different regions of China, maximally reflecting the prescription information of China. Retrieved data included the prescription date, patient gender and age, hospital code and location, indication for anticoagulation, and costs of the anticoagulants. In accordance with the institutional policy of data privacy, patients' ages and prescription dates were interpreted into age and time ranges. Patients were included in this utilization analysis if the following criteria were met: i) presented to the ED in the abovementioned cities between 2016.01.01 and 2019.12.31, ii) diagnosed with VTE (a first case or a recurring case), and iii) received anticoagulants indicated for VTE. Notably, VTE here indicates the disease to be treated by anticoagulants. Thus, patients with pre-existing VTE receiving anticoagulation for other indications (i.e., atrial fibrillation or recovery from orthopedic operations) were not deemed to fulfill the inclusion criteria. Data were washed out if the mentioned demographics and baseline information were incomplete. The primary objective of this utilization analysis is to determine the trend in anticoagulant prescription for VTE treated in the ED (ED-VTE) from 2016 to 2019. Additionally, the average costs of anticoagulants per prescription were calculated. Data analyses were accomplished using the statistical software package SPSS, version 21 (SPSS Inc.). Prescriptions and costs of anticoagulants are presented as frequencies and percentages (n, %). The sample size was not estimated before data collection due to the retrospective nature of the study and the current scarcity of data on anticoagulant prescribing for ED-VTE. Results During the study period between January 2016 and December 2019, a total of 4609 prescriptions on anticoagulants were retrieved and collected from the cooperative data program (Beijing Union Hospital). No incomplete data were identified during the retrieval. The anticoagulants involved in the current study include LMWH, warfarin, dabigatran, and rivaroxaban. Other oral and parenteral anticoagulants were not included in this pharmacological utilization analysis due to insufficient accessibility and scarcity in clinical application. All included anticoagulants were prescribed for the diagnosis of VTE (ICD-10 codes I26, I80, I82, and I27.82). The demographic information of the included patients is shown in Table 1 . Of the included prescriptions, 63.9% were given to patients aged more than 65 years, and 55.0% were given to female patients. The city of Shanghai provided up to half of the prescriptions. In general, LMWH was the most frequent prescribing anticoagulant in EDs. Over 77% of patients who were diagnosed with VTE received a subcutaneous injection of LMWH for anticoagulation; the second most common prescription was the VKA warfarin (14.4%). Table 1 General information on prescriptions Characteristics Total prescriptions (n) 4609 Age (n, %) <65 years 1666 (36.1%) ≥65 years 2943 (63.9%) Gender (n, %) Male 2075 (45.0%) Female 2534 (55.0%) Location (n, %) Beijing 1320 (28.6%) Shanghai 2258 (49.0%) Guangzhou 415 (9.0%) Tianjin 616 (13.4%) Prescription details are described and illustrated in Table 2 and Fig. 1 . The parenteral anticoagulant LMWH remained the most prescribing anticoagulant regardless of time, patient gender, or location. The highest utilization of LMWH was found in 2016 when LMWH was prescribed for more than 80% of general VTE patients. Although this proportion fell downwards through the following years, the most negligible proportion of LMWH remained as high as 74.7% in 2018. Warfarin was the most prescribing oral anticoagulant from 2016 to 2018. Warfarin constitutes more than 60% of all oral anticoagulants during this time frame, followed by rivaroxaban (21.2% − 31.5%). The utilization of rivaroxaban increased to 48.4% of all oral anticoagulants in 2019. Compared to warfarin and rivaroxaban, dabigatran was less prescribed. No prescription on ED dabigatran for VTE was retracted from the database in 2016. By the end of 2019, the utilization of dabigatran increased to 9.8% of all oral anticoagulants. Table 2 Prescription details Prescriptions ( n, % ) Cost ( yuan ) total per prescription LMWH 3560 (77.2%) 319502.62 (69.4%) 89.75 Beijing 1166 88819.83 - Shanghai 1675 161783.78 - Guangzhou 263 27608.40 - Tianjin 456 41290.61 - Warfarin 665 (14.4%) 8991.27 (2.0%) 13.73 Beijing 64 2032.55 - Shanghai 456 6168.33 - Guangzhou 47 166.42 - Tianjin 88 623.97 - Rivaroxaban 332 (7.2%) 108317.08 (23.5%) 326.26 Beijing 84 32791.64 - Shanghai 73 22471.16 - Guangzhou 103 35934.3 - Tianjin 72 17119.98 - Dabigatran 62 (1.3%) 23869.59 (5.2%) 385.00 Beijing 6 927.76 - Shanghai 54 22574.83 - Guangzhou 2 367 - Tianjin 0 0 - Total 4609 460680.56 - Beijing 1320 124571.78 - Shanghai 2258 212998.10 - Guangzhou 415 64076.12 - Tianjin 616 59034.56 - Details on cost are described and illustrated in Table 2 and Fig. 2 . Parenteral anticoagulants accounted for over 60% of the overall cost of ED anticoagulants, as LMWH accounted for the majority of anticoagulant prescriptions. Within the study period, a total of 3560 prescriptions on LMWH cost 319 502.62 yuan (89.75 yuan per prescription), constituting 69.4% (64.1% − 76.0%, yearly) of the total cost of ED anticoagulants. For oral anticoagulants, warfarin, providing 61.9% overall ED oral anticoagulant utilization, accounted for only 2.0% (1.4% − 3.1%, yearly) of the total cost of oral anticoagulants (13.73 yuan per prescription). Rivaroxaban accounted for over 60% of the total cost of oral anticoagulants during the study period. A total of 332 prescriptions cost 108 317.08 yuan (326.26 yuan per prescription). The cost of dabigatran increased with its utilization. By the end of 2019, the cost of dabigatran took on 27.6% of overall oral anticoagulants. The price per prescription for dabigatran is 385.00 yuan, slightly higher than that of rivaroxaban. Discussion In the present population-based drug utilization analysis, the trend in ED anticoagulant prescription for VTE in China was investigated. Retrospective data from four major Chinese cities were retrieved and analyzed as representatives. Between 2016 and 2019, a total of 4609 prescriptions on anticoagulants were prescribed in the ED. LMWH remained the mainstream anticoagulant for patients with VTE in the ED. Increased use of dabigatran and rivaroxaban was presented based on the study results. In contrast, warfarin became less prescribing during the study period. Regarding cost, LMWH contributed more than 60% of the total cost of anticoagulants prescribed for emergent VTE. During the study period, rivaroxaban accounted for the majority of the cost of oral anticoagulants. Expenses on dabigatran were on the rise. To the best of our knowledge, our study is the first drug utilization analysis on ED anticoagulant prescriptions in China. The general incidence of VTE regardless of time period and setting is estimated to be 1 to 2 per 1000 people per year. 16 – 19 Once VTE is diagnosed, rapid-onset anticoagulation should be initiated to relieve the symptoms and prevent thrombus propagation and embolization. 20 Our results revealed that LMWH is still the fundamental anticoagulant in the ED, constituting 74.6–80% of overall ED anticoagulant prescriptions during the study period. Pharmacologically, LMWH are fragments of unfractionated heparin with an average molecular weight of approximately 5000 Da. Since the long heparin chains are fractionated, LMWH hardly inhibits the activities of thrombin (Factor II). 21 In addition, it neither binds to macrophages or endothelial cells nor possesses a strong affinity for heparin-binding plasma proteins. 22 Therefore, LMWH is more predictable in its efficacy than other drugs because of its better bioavailability, longer half-life, and dose-independent clearance and has been recommended by the American College of Chest Physicians (ACCP) ninth edition guidelines as the first-line agent for the initial anticoagulation of VTE patients. 8 After administering initial anticoagulation, long-term anticoagulation should be followed. Before the extensive application of DOACs, LMWH was usually followed by subsequent oral warfarin to maintain a stable international normalized ratio (INR) between 2.0 and 3.0 in the long term. 20 However, the prescriptions of warfarin were not proportional to LMWH in the current study. The authors assume that this deviation can be explained by the bridging period. When following traditional anticoagulation, warfarin should overlap LMWH for a bridging period. The median bridging length was expected to be eight days (IQR 6–11 days) in accordance with clinical trials, although it is sometimes shorter in clinical practice. During the bridging period, patients may turn to outpatients for subsequent treatment after initial LMWH anticoagulation, resulting in fewer warfarin prescriptions. Cost has been demonstrated to have an impact on patients’ selection of anticoagulants. 9 In the present study, parenteral anticoagulant LMWH accounted for over 60% of the overall cost of ED anticoagulants. The average expense of LMWH was 89.75 yuan per prescription, based on the current findings. Given its acceptability in price, nonetheless, the authors assumed that the reasonable expense may not explain the high usage of LMWH, which was recommended as the first-line anticoagulant in most VTE events per the most recent guidelines. 9 For the selection of oral anticoagulants, the average cost affected patients’ choice more remarkably. Our results suggested that warfarin provided 61.9% of the overall oral anticoagulant utilization with 1.4% − 3.1% of the total yearly cost (13.73 yuan per prescription). Despite the inconvenience and higher bleeding risks, more than 60% of the overall patients still had warfarin as their anticoagulation choice. Rivaroxaban (326.26 yuan per prescription) and dabigatran (385.00 yuan per prescription) accounted for over 90% of the total cost of oral anticoagulants in combination, notwithstanding that they were less prescribed than warfarin. The authors assumed that patients who placed a higher value on cost had a higher possibility of choosing warfarin. Nonetheless, as influences beyond price were not examined in the present study, the impact of cost on the selection of anticoagulants should be considered cautiously. Since the introduction of DOACs, the treatment of VTE has dramatically changed. The results from scaled clinical trials indicated that DOACs are not inferior to standard therapy for the initial treatment of PE and symptomatic DVT. 23 , 24 The risk for major bleeding was significantly decreased with DOACs compared to standard therapy. 23 – 25 Real-world studies essentially confirmed the findings of Phase III clinical trials. 26 Due to their predictable pharmacokinetics and pharmacodynamics, DOACs are exempt from the need for regular monitoring of the INR. DOACs are associated with shorter hospitalizations, fewer hospitalizations, and outpatient and ED visits and are recommended as the first choice for initial anticoagulation for patients with VTE unless contraindicated. 11 Our results showed that the prescriptions of DOACs increased extensively over the past years. This finding is in line with several drug utilization studies. 14 , 15 , 27 Prescriptions on warfarin decreased by over 25% within the four-year period. Dabigatran and rivaroxaban accounted for approximately 60% of the total ED oral anticoagulant prescriptions in 2019. The trend in oral anticoagulants is in line with the published literature. 15 On the other hand, the main concerns regarding DOAC use in the ED are contraindications and drug-drug interactions. The therapeutic effectiveness and safety issues of DOACs among the particular population were not examined in the mentioned clinical trials. Patients with liver or renal impairment, pregnancy, active malignancy, expectations of surgery, and other extreme clinical statuses are not capable of DOACs. In addition, a number of medications can interact with the blood concentration of DOACs. Given the complexity of ED patients, prescribing DOACs for acute PE and symptomatic DVT is at risk of poorer clinical outcomes. For patients contraindicated or underlyingly contraindicated to DOACs, LMWH is preferred for initial anticoagulation because of its safety. Additionally, this agent must be injected subcutaneously by a healthcare worker. With LMWH, from the doctors' perspective, even patients with poor compliance are expected to receive a standard treatment. This advantage of LMWH may decrease the risks for overdose or missed dose, especially for those who cannot take care of themselves. In addition to the above considerations, the selection of anticoagulants is also based on patients' preferences. Our study has several limitations. Given its retrospective nature and data retracting limitations, more detailed information concerning demographics (e.g., patients' age, education, income, exact diagnosis (PE or DVT)) and prescriptions (e.g., dosage, course) was lacking in our analysis. The imbalanced inclusion of medical settings may result in selection bias. Furthering analyses are expected to investigate the trend in ED-VTE anticoagulant prescription. Conclusions This drug utilization analysis aims to investigate the current status of anticoagulant prescription among ED-VTE patients and describe its trend. Our results revealed that LMWH remains the most prescribing anticoagulant regardless of time, sex, and medical institution location. The overall consumption of DOACs increased in the ED during the study period. Warfarin was the most prescribing oral anticoagulant from 2016 to 2018 and was replaced by rivaroxaban in 2019. The costs of DOACs are exceptionally higher than those of LMWH in the ED. The selection of anticoagulants in the ED is complex. Further investigations are warranted. Declarations Ethics approval and consent to participate The consent to participate was deemed unnecessary, and was waived by Ethics Committee of Peking Union Medical College Hospital. The Ethics Committee of Peking Union Medical College Hospital approved the present study. Consent for publication Not applicable. Competing interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Funding This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Authors' contributions W Guo and ZG Zhao conceived and designed this study. X Liu collected data. X Wang and X Liu performed the statistical analyses and wrote the first draft of the manuscript. W Guo and ZG Zhao reviewed and modified the final manuscript. All authors read, critically reviewed and approved the final manuscript. Acknowledgements We are particularly grateful to Peking Union Medical College Hospital for providing data. References Bartholomew JR. Update on the management of venous thromboembolism. Clev Clin J Med 2017; 84: 39–46. Raskob GE, Angchaisuksiri P, Blanco AN, et al. Thrombosis Thrombosis A Major Contributor to Global Disease Burden. Arteriosclerosis Thrombosis Vasc Biology 2014; 34: 2363–2371. Tagalakis V, Patenaude V, Kahn SR, et al. Incidence of and Mortality from Venous Thromboembolism in a Real-world Population: The Q-VTE Study Cohort. Am J Medicine 2013; 126: 832.e13-832.e21. Bikdeli B, Wang Y, Jimenez D, et al. Pulmonary Embolism Hospitalization, Readmission, and Mortality Rates in US Older Adults, 1999-2015. Jama 2019; 322: 574–576. Khan F, Tritschler T, Kahn SR, et al. Venous thromboembolism. Lancet 2021; 398: 64–77. Nicolaides AN, Fareed J, Kakkar AK, et al. 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Papakonstantinou PE, Tsioufis C, Konstantinidis D, et al. Anticoagulation in Deep Venous Thrombosis: Current Trends in the Era of Non-Vitamin K Antagonists Oral Anticoagulants. Curr Pharm Design 2020; 26: 2692–2702. Cite Share Download PDF Status: Posted Version 1 posted 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. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-1878216","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":149094117,"identity":"b9f95d01-0d90-4e4e-ad13-b40f718350e8","order_by":0,"name":"Xia Wang","email":"","orcid":"","institution":"Beijing Tiantan Hospital","correspondingAuthor":false,"prefix":"","firstName":"Xia","middleName":"","lastName":"Wang","suffix":""},{"id":149094118,"identity":"cc672714-2ff7-4a7c-b837-07d63fd3cb02","order_by":1,"name":"Xin Liu","email":"","orcid":"","institution":"Beijing Tiantan Hospital","correspondingAuthor":false,"prefix":"","firstName":"Xin","middleName":"","lastName":"Liu","suffix":""},{"id":149094119,"identity":"c4dd4de5-f2df-450d-bd93-119fe317c230","order_by":2,"name":"Zhigang Zhao","email":"","orcid":"","institution":"Beijing Tiantan Hospital","correspondingAuthor":false,"prefix":"","firstName":"Zhigang","middleName":"","lastName":"Zhao","suffix":""},{"id":149094120,"identity":"32e272f0-c093-4a11-ba53-15238068d2c0","order_by":3,"name":"Wei Guo","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAzElEQVRIiWNgGAWjYNACAwkeNmbmAwc+VBCvxUKOj70t8eCMM8RbU2Esx3PG+DBvCxFq5SOSj0l8KJBIbJPI+XCAt4FBnl/sAH4thjfS0iRnGIC05G44ILmDwXDm7AQCWmbkmN3mgWkxPMOQYHCbGC1/wFpyHhxIbCNCi7wEUAswkI3ZeM4wHDhIjBYDnmfpP3sMJOTY2NsMDjackSDsF/n25MMGP/7U8cg3Mz/+/KfCRp5fmpAtB1D5EviVg21pIKxmFIyCUTAKRjoAADVBRa5pfQdxAAAAAElFTkSuQmCC","orcid":"https://orcid.org/0000-0003-2453-1589","institution":"Beijing Tiantan Hospital","correspondingAuthor":true,"prefix":"","firstName":"Wei","middleName":"","lastName":"Guo","suffix":""}],"badges":[],"createdAt":"2022-07-20 13:41:37","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-1878216/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-1878216/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":28752470,"identity":"bef5ecd5-a7d7-4494-a48a-f0be46b06dcf","added_by":"auto","created_at":"2022-11-07 15:03:19","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":48579,"visible":true,"origin":"","legend":"\u003cp\u003ePrescriptions for anticoagulants in the ED between 2016 and 2019. Fig 1a, proportions of prescriptions for oral and parenteral (LMWH) anticoagulants; Fig 1b, proportions of prescriptions for rivaroxaban, dabigatran, and warfarin. LMWH, low-molecular-weight heparin.\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-1878216/v1/949ada983e237d3944c3b5a9.png"},{"id":28752469,"identity":"c05d2b14-4339-47b9-93af-3c61c4125707","added_by":"auto","created_at":"2022-11-07 15:03:19","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":51703,"visible":true,"origin":"","legend":"\u003cp\u003eCost of ED anticoagulant prescription between 2016 and 2019. Fig 2a, costs of oral and parenteral (LMWH) anticoagulants as proportions of total cost; Fig 2b, costs of rivaroxaban, dabigatran, and warfarin as proportions of total cost. LMWH, low-molecular-weight heparin.\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-1878216/v1/0610714acc962c7bcd9fa782.png"},{"id":31254498,"identity":"96405b8c-b05c-4254-babd-4197610a32c5","added_by":"auto","created_at":"2023-01-07 11:16:17","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":300787,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-1878216/v1/43348d55-c6c7-4d81-aa1c-cbcfda16ca56.pdf"}],"financialInterests":"","formattedTitle":"Trends in Emergency Department Anticoagulant Prescription for Patients with Venous Thromboembolism in China, 2016-2019","fulltext":[{"header":"Introduction","content":"\u003cp\u003eVenous thromboembolism (VTE), clinically presenting as deep vein thrombosis (DVT) and pulmonary embolism (PE), is a major contributor to the global burden of disease and affects nearly 10\u0026nbsp;million people worldwide each year.\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e,\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e VTE is commonly diagnosed in the emergency department (ED) and ranks as the third most frequent acute cardiovascular syndrome, behind myocardial infarction and stroke.\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e VTE is a fatal disease. It has been reported that almost 5% of patients die within a week after the diagnosis of PE, and one-fifth of patients who have experienced an index VTE event die within a year. \u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e,\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e In consideration of the catastrophic consequence of untreated acute VTE, computed tomography pulmonary angiography (CTPA) and compression ultrasonography are widely utilized to identify suspected VTE patients in the ED, which creates onerous diagnosis and management burdens for ED physicians.\u003c/p\u003e \u003cp\u003eOnce VTE is diagnosed, patients should be anticoagulated to prevent thrombus extension, embolism, recurrence, death, and other long-term complications.\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e Managements for VTE involve anticoagulation, thrombolysis, vena cava filters, elastic compression, and other supportive therapies, among which anticoagulation remains the cornerstone. Anticoagulation therapy is expected to be maintained for at least 3 to 6 months to minimize the risks for thrombus recurrence.\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e Long-term administration of anticoagulants is weighed as an option by comparing the risk of VTE events to the risk of major bleeding.\u003csup\u003e\u003cspan additionalcitationids=\"CR7 CR8\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e Anticoagulants for VTE include unfractionated heparin (UFH), low-molecular-weight heparin (LMWH), vitamin K\u0026ndash;dependent antagonists (VKAs, i.e., warfarin), and direct oral anticoagulants (DOACs). Anticoagulation therapy for an acute VTE event includes initial anticoagulation (systemic anticoagulation during the first few days after a VTE diagnosis), long-term anticoagulation (anticoagulation beyond the initial period, usually three to twelve months), and extended anticoagulation (anticoagulation that is administered indefinitely) if needed. The therapeutic effects and safety of the above agents differ depending on patients' conditions and comorbidities. Abundant clinical trials indicate that DOACs and VKAs produce comparable effects on symptomatic VTE, while DOACs are associated with a reduced risk of major bleeding and reduced healthcare demands.\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e,\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e In clinical practice, however, the selection of anticoagulants is complex.\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e It relies on medical considerations and availability, patient comorbidities, preferences, convenience, and financial situations. Vitamin-K antagonists remain the most widely used anticoagulation drug in the ED, although improving evidence suggests that DOACs are more viable and cost effective than conventional anticoagulation among acute VTE patients.\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e,\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eSeveral studies have been conducted to investigate the prescription of anticoagulants in VTE patients to obtain an extensive understanding of this gap between medical recommendations and clinical practice.\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e,\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e However, little is known concerning the trend in anticoagulant prescription for ED patients with VTE.\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e The current study retrieved all available prescriptions of anticoagulants from the EDs of four major cities in China as representatives. This demographic study aims to investigate the status of anticoagulant prescription for Chinese VTE patients and describe the trend in their use.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eThe current study is a population-based drug utilization study conducted to investigate the status and trend in anticoagulant prescriptions among patients diagnosed with VTE (ICD-10 codes I26, I80, I82, and I27.82) in the ED of four major Chinese cities (Beijing, Tianjin, Shanghai, and Guangzhou) between 2016 and 2019. All data were retrieved from a corporative data program constructed by the Peking Union Medical College Hospital, compromising more than 100 hospitals in thirty-five Chinese cities. The pharmacy prescriptions were recorded in bins of ten consecutive days. The included medical institutions covered more than 500\u0026nbsp;million patients and were located in different regions of China, maximally reflecting the prescription information of China.\u003c/p\u003e \u003cp\u003eRetrieved data included the prescription date, patient gender and age, hospital code and location, indication for anticoagulation, and costs of the anticoagulants. In accordance with the institutional policy of data privacy, patients' ages and prescription dates were interpreted into age and time ranges. Patients were included in this utilization analysis if the following criteria were met: i) presented to the ED in the abovementioned cities between 2016.01.01 and 2019.12.31, ii) diagnosed with VTE (a first case or a recurring case), and iii) received anticoagulants indicated for VTE. Notably, VTE here indicates the disease to be treated by anticoagulants. Thus, patients with pre-existing VTE receiving anticoagulation for other indications (i.e., atrial fibrillation or recovery from orthopedic operations) were not deemed to fulfill the inclusion criteria. Data were washed out if the mentioned demographics and baseline information were incomplete.\u003c/p\u003e \u003cp\u003eThe primary objective of this utilization analysis is to determine the trend in anticoagulant prescription for VTE treated in the ED (ED-VTE) from 2016 to 2019. Additionally, the average costs of anticoagulants per prescription were calculated. Data analyses were accomplished using the statistical software package SPSS, version 21 (SPSS Inc.). Prescriptions and costs of anticoagulants are presented as frequencies and percentages (n, %). The sample size was not estimated before data collection due to the retrospective nature of the study and the current scarcity of data on anticoagulant prescribing for ED-VTE.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eDuring the study period between January 2016 and December 2019, a total of 4609 prescriptions on anticoagulants were retrieved and collected from the cooperative data program (Beijing Union Hospital). No incomplete data were identified during the retrieval. The anticoagulants involved in the current study include LMWH, warfarin, dabigatran, and rivaroxaban. Other oral and parenteral anticoagulants were not included in this pharmacological utilization analysis due to insufficient accessibility and scarcity in clinical application. All included anticoagulants were prescribed for the diagnosis of VTE (ICD-10 codes I26, I80, I82, and I27.82). The demographic information of the included patients is shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Of the included prescriptions, 63.9% were given to patients aged more than 65 years, and 55.0% were given to female patients. The city of Shanghai provided up to half of the prescriptions. In general, LMWH was the most frequent prescribing anticoagulant in EDs. Over 77% of patients who were diagnosed with VTE received a subcutaneous injection of LMWH for anticoagulation; the second most common prescription was the VKA warfarin (14.4%).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eGeneral information on prescriptions\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal prescriptions (n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003e4609\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (n, %)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003e\u0026lt;65 years\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003e1666 (36.1%)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003e\u0026ge;65 years\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003e2943 (63.9%)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGender (n, %)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eMale\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003e2075 (45.0%)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eFemale\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003e2534 (55.0%)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLocation (n, %)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eBeijing\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003e1320 (28.6%)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eShanghai\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003e2258 (49.0%)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eGuangzhou\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003e415 (9.0%)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eTianjin\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003e616 (13.4%)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003ePrescription details are described and illustrated in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e and Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The parenteral anticoagulant LMWH remained the most prescribing anticoagulant regardless of time, patient gender, or location. The highest utilization of LMWH was found in 2016 when LMWH was prescribed for more than 80% of general VTE patients. Although this proportion fell downwards through the following years, the most negligible proportion of LMWH remained as high as 74.7% in 2018. Warfarin was the most prescribing oral anticoagulant from 2016 to 2018. Warfarin constitutes more than 60% of all oral anticoagulants during this time frame, followed by rivaroxaban (21.2% \u0026minus;\u0026thinsp;31.5%). The utilization of rivaroxaban increased to 48.4% of all oral anticoagulants in 2019. Compared to warfarin and rivaroxaban, dabigatran was less prescribed. No prescription on ED dabigatran for VTE was retracted from the database in 2016. By the end of 2019, the utilization of dabigatran increased to 9.8% of all oral anticoagulants.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePrescription details\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePrescriptions (\u003cem\u003en, %\u003c/em\u003e)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003eCost (\u003cem\u003eyuan\u003c/em\u003e)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003etotal\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003eper prescription\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eLMWH\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003e3560 (77.2%)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003e319502.62 (69.4%)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003e89.75\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eBeijing\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003e1166\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003e88819.83\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003e-\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eShanghai\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003e1675\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003e161783.78\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003e-\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eGuangzhou\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003e263\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003e27608.40\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003e-\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eTianjin\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003e456\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003e41290.61\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003e-\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eWarfarin\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003e665 (14.4%)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003e8991.27 (2.0%)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003e13.73\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eBeijing\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003e64\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003e2032.55\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003e-\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eShanghai\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003e456\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003e6168.33\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003e-\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eGuangzhou\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003e47\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003e166.42\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003e-\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eTianjin\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003e88\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003e623.97\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003e-\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eRivaroxaban\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003e332 (7.2%)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003e108317.08 (23.5%)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003e326.26\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eBeijing\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003e84\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003e32791.64\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003e-\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eShanghai\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003e73\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003e22471.16\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003e-\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eGuangzhou\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003e103\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003e35934.3\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003e-\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eTianjin\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003e72\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003e17119.98\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003e-\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eDabigatran\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003e62 (1.3%)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003e23869.59 (5.2%)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003e385.00\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eBeijing\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003e6\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003e927.76\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003e-\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eShanghai\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003e54\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003e22574.83\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003e-\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eGuangzhou\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003e2\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003e367\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003e-\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eTianjin\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003e0\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003e0\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003e-\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eTotal\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003e4609\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003e460680.56\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003e-\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eBeijing\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003e1320\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003e124571.78\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003e-\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eShanghai\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003e2258\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003e212998.10\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003e-\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eGuangzhou\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003e415\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003e64076.12\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003e-\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eTianjin\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003e616\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003e59034.56\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003e-\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eDetails on cost are described and illustrated in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e and Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. Parenteral anticoagulants accounted for over 60% of the overall cost of ED anticoagulants, as LMWH accounted for the majority of anticoagulant prescriptions. Within the study period, a total of 3560 prescriptions on LMWH cost 319 502.62 yuan (89.75 yuan per prescription), constituting 69.4% (64.1% \u0026minus;\u0026thinsp;76.0%, yearly) of the total cost of ED anticoagulants. For oral anticoagulants, warfarin, providing 61.9% overall ED oral anticoagulant utilization, accounted for only 2.0% (1.4% \u0026minus;\u0026thinsp;3.1%, yearly) of the total cost of oral anticoagulants (13.73 yuan per prescription). Rivaroxaban accounted for over 60% of the total cost of oral anticoagulants during the study period. A total of 332 prescriptions cost 108 317.08 yuan (326.26 yuan per prescription). The cost of dabigatran increased with its utilization. By the end of 2019, the cost of dabigatran took on 27.6% of overall oral anticoagulants. The price per prescription for dabigatran is 385.00 yuan, slightly higher than that of rivaroxaban.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn the present population-based drug utilization analysis, the trend in ED anticoagulant prescription for VTE in China was investigated. Retrospective data from four major Chinese cities were retrieved and analyzed as representatives. Between 2016 and 2019, a total of 4609 prescriptions on anticoagulants were prescribed in the ED. LMWH remained the mainstream anticoagulant for patients with VTE in the ED. Increased use of dabigatran and rivaroxaban was presented based on the study results. In contrast, warfarin became less prescribing during the study period. Regarding cost, LMWH contributed more than 60% of the total cost of anticoagulants prescribed for emergent VTE. During the study period, rivaroxaban accounted for the majority of the cost of oral anticoagulants. Expenses on dabigatran were on the rise. To the best of our knowledge, our study is the first drug utilization analysis on ED anticoagulant prescriptions in China.\u003c/p\u003e \u003cp\u003eThe general incidence of VTE regardless of time period and setting is estimated to be 1 to 2 per 1000 people per year. \u003csup\u003e\u003cspan additionalcitationids=\"CR17 CR18\" citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e Once VTE is diagnosed, rapid-onset anticoagulation should be initiated to relieve the symptoms and prevent thrombus propagation and embolization.\u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e Our results revealed that LMWH is still the fundamental anticoagulant in the ED, constituting 74.6\u0026ndash;80% of overall ED anticoagulant prescriptions during the study period. Pharmacologically, LMWH are fragments of unfractionated heparin with an average molecular weight of approximately 5000 Da. Since the long heparin chains are fractionated, LMWH hardly inhibits the activities of thrombin (Factor II).\u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e In addition, it neither binds to macrophages or endothelial cells nor possesses a strong affinity for heparin-binding plasma proteins.\u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e Therefore, LMWH is more predictable in its efficacy than other drugs because of its better bioavailability, longer half-life, and dose-independent clearance and has been recommended by the American College of Chest Physicians (ACCP) ninth edition guidelines as the first-line agent for the initial anticoagulation of VTE patients.\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e After administering initial anticoagulation, long-term anticoagulation should be followed. Before the extensive application of DOACs, LMWH was usually followed by subsequent oral warfarin to maintain a stable international normalized ratio (INR) between 2.0 and 3.0 in the long term.\u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e However, the prescriptions of warfarin were not proportional to LMWH in the current study. The authors assume that this deviation can be explained by the bridging period. When following traditional anticoagulation, warfarin should overlap LMWH for a bridging period. The median bridging length was expected to be eight days (IQR 6\u0026ndash;11 days) in accordance with clinical trials, although it is sometimes shorter in clinical practice. During the bridging period, patients may turn to outpatients for subsequent treatment after initial LMWH anticoagulation, resulting in fewer warfarin prescriptions.\u003c/p\u003e \u003cp\u003eCost has been demonstrated to have an impact on patients\u0026rsquo; selection of anticoagulants.\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e In the present study, parenteral anticoagulant LMWH accounted for over 60% of the overall cost of ED anticoagulants. The average expense of LMWH was 89.75 yuan per prescription, based on the current findings. Given its acceptability in price, nonetheless, the authors assumed that the reasonable expense may not explain the high usage of LMWH, which was recommended as the first-line anticoagulant in most VTE events per the most recent guidelines.\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e For the selection of oral anticoagulants, the average cost affected patients\u0026rsquo; choice more remarkably. Our results suggested that warfarin provided 61.9% of the overall oral anticoagulant utilization with 1.4% \u0026minus;\u0026thinsp;3.1% of the total yearly cost (13.73 yuan per prescription). Despite the inconvenience and higher bleeding risks, more than 60% of the overall patients still had warfarin as their anticoagulation choice. Rivaroxaban (326.26 yuan per prescription) and dabigatran (385.00 yuan per prescription) accounted for over 90% of the total cost of oral anticoagulants in combination, notwithstanding that they were less prescribed than warfarin. The authors assumed that patients who placed a higher value on cost had a higher possibility of choosing warfarin. Nonetheless, as influences beyond price were not examined in the present study, the impact of cost on the selection of anticoagulants should be considered cautiously.\u003c/p\u003e \u003cp\u003eSince the introduction of DOACs, the treatment of VTE has dramatically changed. The results from scaled clinical trials indicated that DOACs are not inferior to standard therapy for the initial treatment of PE and symptomatic DVT.\u003csup\u003e\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e,\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e The risk for major bleeding was significantly decreased with DOACs compared to standard therapy.\u003csup\u003e\u003cspan additionalcitationids=\"CR24\" citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e Real-world studies essentially confirmed the findings of Phase III clinical trials.\u003csup\u003e\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e Due to their predictable pharmacokinetics and pharmacodynamics, DOACs are exempt from the need for regular monitoring of the INR. DOACs are associated with shorter hospitalizations, fewer hospitalizations, and outpatient and ED visits and are recommended as the first choice for initial anticoagulation for patients with VTE unless contraindicated.\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e Our results showed that the prescriptions of DOACs increased extensively over the past years. This finding is in line with several drug utilization studies.\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e,\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e,\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e Prescriptions on warfarin decreased by over 25% within the four-year period. Dabigatran and rivaroxaban accounted for approximately 60% of the total ED oral anticoagulant prescriptions in 2019. The trend in oral anticoagulants is in line with the published literature.\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e On the other hand, the main concerns regarding DOAC use in the ED are contraindications and drug-drug interactions. The therapeutic effectiveness and safety issues of DOACs among the particular population were not examined in the mentioned clinical trials. Patients with liver or renal impairment, pregnancy, active malignancy, expectations of surgery, and other extreme clinical statuses are not capable of DOACs. In addition, a number of medications can interact with the blood concentration of DOACs. Given the complexity of ED patients, prescribing DOACs for acute PE and symptomatic DVT is at risk of poorer clinical outcomes. For patients contraindicated or underlyingly contraindicated to DOACs, LMWH is preferred for initial anticoagulation because of its safety. Additionally, this agent must be injected subcutaneously by a healthcare worker. With LMWH, from the doctors' perspective, even patients with poor compliance are expected to receive a standard treatment. This advantage of LMWH may decrease the risks for overdose or missed dose, especially for those who cannot take care of themselves. In addition to the above considerations, the selection of anticoagulants is also based on patients' preferences.\u003c/p\u003e \u003cp\u003eOur study has several limitations. Given its retrospective nature and data retracting limitations, more detailed information concerning demographics (e.g., patients' age, education, income, exact diagnosis (PE or DVT)) and prescriptions (e.g., dosage, course) was lacking in our analysis. The imbalanced inclusion of medical settings may result in selection bias. Furthering analyses are expected to investigate the trend in ED-VTE anticoagulant prescription.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eThis drug utilization analysis aims to investigate the current status of anticoagulant prescription among ED-VTE patients and describe its trend. Our results revealed that LMWH remains the most prescribing anticoagulant regardless of time, sex, and medical institution location. The overall consumption of DOACs increased in the ED during the study period. Warfarin was the most prescribing oral anticoagulant from 2016 to 2018 and was replaced by rivaroxaban in 2019. The costs of DOACs are exceptionally higher than those of LMWH in the ED. The selection of anticoagulants in the ED is complex. Further investigations are warranted.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe consent to participate was deemed unnecessary, and was waived by Ethics Committee of Peking Union Medical College Hospital. The Ethics Committee of Peking Union Medical College Hospital approved the present study.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eW Guo and ZG Zhao conceived and designed this study. X Liu collected data. X Wang and X Liu performed the statistical analyses and wrote the first draft of the manuscript. W Guo and ZG Zhao reviewed and modified the final manuscript. All authors read, critically reviewed and approved the final manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe are particularly grateful to Peking Union Medical College Hospital for providing data.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eBartholomew JR. Update on the management of venous thromboembolism. \u003cem\u003eClev Clin J Med\u003c/em\u003e 2017; 84: 39\u0026ndash;46.\u003c/li\u003e\n\u003cli\u003eRaskob GE, Angchaisuksiri P, Blanco AN, et al. Thrombosis Thrombosis A Major Contributor to Global Disease Burden. \u003cem\u003eArteriosclerosis Thrombosis Vasc Biology\u003c/em\u003e 2014; 34: 2363\u0026ndash;2371.\u003c/li\u003e\n\u003cli\u003eTagalakis V, Patenaude V, Kahn SR, et al. Incidence of and Mortality from Venous Thromboembolism in a Real-world Population: The Q-VTE Study Cohort. \u003cem\u003eAm J Medicine\u003c/em\u003e 2013; 126: 832.e13-832.e21.\u003c/li\u003e\n\u003cli\u003eBikdeli B, Wang Y, Jimenez D, et al. Pulmonary Embolism Hospitalization, Readmission, and Mortality Rates in US Older Adults, 1999-2015. \u003cem\u003eJama\u003c/em\u003e 2019; 322: 574\u0026ndash;576.\u003c/li\u003e\n\u003cli\u003eKhan F, Tritschler T, Kahn SR, et al. Venous thromboembolism. \u003cem\u003eLancet\u003c/em\u003e 2021; 398: 64\u0026ndash;77.\u003c/li\u003e\n\u003cli\u003eNicolaides AN, Fareed J, Kakkar AK, et al. Prevention and treatment of venous thromboembolism--International Consensus Statement. \u003cem\u003eInt Angiology J Int Union Angiology\u003c/em\u003e 2013; 32: 111\u0026ndash;260.\u003c/li\u003e\n\u003cli\u003eBaglin T, Bauer K, Douketis J, et al. Duration of anticoagulant therapy after a first episode of an unprovoked pulmonary embolus or deep vein thrombosis: guidance from the SSC of the ISTH. \u003cem\u003eJ Thromb Haemost\u003c/em\u003e 2012; 10: 698\u0026ndash;702.\u003c/li\u003e\n\u003cli\u003eKearon C, Akl EA, Comerota AJ, et al. Antithrombotic Therapy for VTE Disease Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. \u003cem\u003eChest\u003c/em\u003e 2012; 141: e419S-e496S.\u003c/li\u003e\n\u003cli\u003eKearon C, Akl EA, Ornelas J, et al. Antithrombotic Therapy for VTE Disease CHEST Guideline and Expert Panel Report. \u003cem\u003eChest\u003c/em\u003e 2016; 149: 315\u0026ndash;352.\u003c/li\u003e\n\u003cli\u003eEs N van, Coppens M, Schulman S, et al. Direct oral anticoagulants compared with vitamin K antagonists for acute venous thromboembolism: evidence from phase 3 trials. \u003cem\u003eBlood\u003c/em\u003e 2014; 124: 1968\u0026ndash;1975.\u003c/li\u003e\n\u003cli\u003eLutsey PL, MacLehose RF, Claxton JS, et al. Impact of oral anticoagulation choice on healthcare utilization for the primary treatment of venous thromboembolism. \u003cem\u003eVasc Med\u003c/em\u003e 2020; 25: 549\u0026ndash;556.\u003c/li\u003e\n\u003cli\u003eEschler CM, Woitok BK, Funk G-C, et al. Oral Anticoagulation in Patients in the Emergency Department: High Rates of Off-Label Doses, No Difference in Bleeding Rates. \u003cem\u003eAm J Medicine\u003c/em\u003e 2020; 133: 599\u0026ndash;604.\u003c/li\u003e\n\u003cli\u003eLaw S, Ghag D, Grafstein E, et al. A pharmacoeconomic study of traditional anticoagulation versus direct oral anticoagulation for the treatment of venous thromboembolism in the emergency department. \u003cem\u003eCjem\u003c/em\u003e 2016; 18: 340\u0026ndash;348.\u003c/li\u003e\n\u003cli\u003eGhanima W, Schultze A, Donaldson R, et al. Oral Anticoagulation Therapy for Venous Thromboembolism in Norway: Time Trends and Treatment Patterns. \u003cem\u003eClin Ther\u003c/em\u003e. Epub ahead of print 2021. DOI: 10.1016/j.clinthera.2021.04.017.\u003c/li\u003e\n\u003cli\u003eLutsey PL, Walker RF, MacLehose RF, et al. Direct oral anticoagulants and warfarin for venous thromboembolism treatment: Trends from 2012 to 2017. \u003cem\u003eRes Pract Thrombosis Haemostasis\u003c/em\u003e 2019; 3: 668\u0026ndash;673.\u003c/li\u003e\n\u003cli\u003eSchissler AJ, Rozenshtein A, Schluger NW, et al. National trends in emergency room diagnosis of pulmonary embolism, 2001\u0026ndash;2010: a cross-sectional study. \u003cem\u003eRespir Res\u003c/em\u003e 2015; 16: 44.\u003c/li\u003e\n\u003cli\u003eBou\u0026eacute;e S, Emery C, Samson A, et al. Incidence of venous thromboembolism in France: a retrospective analysis of a national insurance claims database. \u003cem\u003eThrombosis J\u003c/em\u003e 2016; 14: 4.\u003c/li\u003e\n\u003cli\u003eM\u0026uuml;nster AM, Rasmussen TB, Falstie-Jensen AM, et al. A changing landscape: Temporal trends in incidence and characteristics of patients hospitalized with venous thromboembolism 2006\u0026ndash;2015. \u003cem\u003eThromb Res\u003c/em\u003e 2019; 176: 46\u0026ndash;53.\u003c/li\u003e\n\u003cli\u003eArshad N, Isaksen T, Hansen J-B, et al. Time trends in incidence rates of venous thromboembolism in a large cohort recruited from the general population. \u003cem\u003eEur J Epidemiol\u003c/em\u003e 2017; 32: 299\u0026ndash;305.\u003c/li\u003e\n\u003cli\u003eOrtel TL, Neumann I, Ageno W, et al. American Society of Hematology 2020 guidelines for management of venous thromboembolism: treatment of deep vein thrombosis and pulmonary embolism. \u003cem\u003eBlood Adv\u003c/em\u003e 2020; 4: 4693\u0026ndash;4738.\u003c/li\u003e\n\u003cli\u003eOlson S, Swanson R, Raub-Segall E, et al. Accelerating ability of synthetic oligosaccharides on antithrombin inhibition of proteinases of the clotting and fibrinolytic systems Comparison with heparin and low-molecular-weight heparin. \u003cem\u003eThromb Haemostasis\u003c/em\u003e 2004; 92: 929\u0026ndash;939.\u003c/li\u003e\n\u003cli\u003eHirsh J, Levine MN. Low molecular weight heparin. \u003cem\u003eBlood\u003c/em\u003e 1992; 79: 1\u0026ndash;17.\u003c/li\u003e\n\u003cli\u003eSchulman S, Kearon C, Kakkar AK, et al. Dabigatran versus Warfarin in the Treatment of Acute Venous Thromboembolism. \u003cem\u003eNew Engl J Medicine\u003c/em\u003e 2009; 361: 2342\u0026ndash;2352.\u003c/li\u003e\n\u003cli\u003eInvestigators E, Bauersachs R, Berkowitz SD, et al. Oral Rivaroxaban for Symptomatic Venous Thromboembolism. \u003cem\u003eNew Engl J Medicine\u003c/em\u003e 2010; 363: 2499\u0026ndash;2510.\u003c/li\u003e\n\u003cli\u003eInvestigators E, B\u0026uuml;ller HR, Prins MH, et al. Oral Rivaroxaban for the Treatment of Symptomatic Pulmonary Embolism. \u003cem\u003eNew Engl J Medicine\u003c/em\u003e 2012; 366: 1287\u0026ndash;1297.\u003c/li\u003e\n\u003cli\u003eBeyer-Westendorf J. What have we learned from real-world NOAC studies in venous thromboembolism treatment? \u003cem\u003eThromb Res\u003c/em\u003e 2018; 163: 83\u0026ndash;91.\u003c/li\u003e\n\u003cli\u003ePapakonstantinou PE, Tsioufis C, Konstantinidis D, et al. Anticoagulation in Deep Venous Thrombosis: Current Trends in the Era of Non-Vitamin K Antagonists Oral Anticoagulants. \u003cem\u003eCurr Pharm Design\u003c/em\u003e 2020; 26: 2692\u0026ndash;2702.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Venous thromboembolism, anticoagulation, emergency department, China","lastPublishedDoi":"10.21203/rs.3.rs-1878216/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-1878216/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eIntroduction:\u003c/h2\u003e \u003cp\u003eUntreated acute venous thromboembolism (VTE) can have catastrophic consequences. Patients should be anticoagulated as soon as VTE is diagnosed. Based on the current clinical guidelines, direct oral anticoagulants (DOACs) are recommended as the first-line anticoagulant treatment for VTE. However, the selection of anticoagulants is a complex task, especially in the emergency department (ED).\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThis population-based drug utilization study was conducted to investigate the status of anticoagulant prescriptions for VTE treated in the ED (ED-VTE; ICD-10 codes I26, I80, I82, and I27.82) and the trend in these prescriptions in four major Chinese cities (Beijing, Tianjin, Shanghai, and Guangzhou) between 2016.1.1 and 2019.12.31. All data were retrieved from a cooperative data program established by the Peking Union Medical College Hospital. Patients who were anticoagulated for initial or recurrent VTE in the EDs of participating institutions during the study period were included in the present analysis. The primary objective was to characterize the trend in anticoagulant prescriptions for ED-VTE; the secondary objective was to calculate the average cost of anticoagulants per prescription. The sample size was not estimated before data collection due to the retrospective nature of the study and the current scarcity of data on anticoagulant prescribing for ED-VTE.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003ea total of 4609 prescriptions for anticoagulants were retrieved; none of these records was found to have incomplete data. The anticoagulants prescribed in the current study included low-molecular-weight heparin (LMWH), warfarin, dabigatran, and rivaroxaban. Of the included prescriptions, 63.9% were given to patients over 65 years old, and 55.0% were given to females. The city of Shanghai accounted for nearly half of the prescriptions. Generally, LMWH was the most frequently prescribed anticoagulant in the ED. Warfarin accounted for more than 60% of all oral anticoagulant prescriptions during the study period; the second most prescribed oral anticoagulant was rivaroxaban (32.1%). The utilization of rivaroxaban increased to 48.4% of all oral anticoagulants in 2019. Dabigatran was less frequently prescribed.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eThe selection of anticoagulants in the ED was complex. LMWH remained the most prescribed anticoagulant regardless of time, gender, institution location, or cost. Warfarin was the most prescribed oral anticoagulant from 2016 to 2018, but the number of rivaroxaban prescriptions exceeded the number of warfarin prescriptions in 2019. DOACs accounted for an increasing share of anticoagulant prescriptions during the study period. Further investigations are warranted.\u003c/p\u003e","manuscriptTitle":"Trends in Emergency Department Anticoagulant Prescription for Patients with Venous Thromboembolism in China, 2016-2019","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2022-11-07 15:03:14","doi":"10.21203/rs.3.rs-1878216/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"eb606b7f-e60d-43df-8cd2-0c5bef1c0e30","owner":[],"postedDate":"November 7th, 2022","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2023-01-07T11:16:10+00:00","versionOfRecord":[],"versionCreatedAt":"2022-11-07 15:03:14","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-1878216","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-1878216","identity":"rs-1878216","version":["v1"]},"buildId":"_2-kVJe1T_tPrBINL-cwx","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}