Impact of an Anticoagulation Management Service-led Intervention on Rates of Antiplatelet and Gastric Bleeding Prophylaxis Use in Ambulatory Care Patients on Background Direct Oral Anticoagulants

Impact of an Anticoagulation Management Service-led Intervention on Rates of Antiplatelet and Gastric Bleeding Prophylaxis Use in Ambulatory Care Patients on Background Direct Oral Anticoagulants | 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 Impact of an Anticoagulation Management Service-led Intervention on Rates of Antiplatelet and Gastric Bleeding Prophylaxis Use in Ambulatory Care Patients on Background Direct Oral Anticoagulants Chau Hoang, Peter Collins, David DeiCicchi, Ewan McNicol, Devan Hawkins, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8081005/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 29 Apr, 2026 Read the published version in Journal of Thrombosis and Thrombolysis → Version 1 posted You are reading this latest preprint version Abstract Background: Patients on long-term anticoagulation face increased bleeding risk when antiplatelets are co-prescribed, especially upper gastrointestinal (GI) bleeding. Guidelines recommend limiting antiplatelet use to highly select patients on background anticoagulants and promoting GI prophylaxis with proton pump inhibitors (PPIs) for those requiring dual antithrombotic therapy. Objectives: To assess the impact of an anticoagulation management service (AMS)-led intervention on reducing excess antiplatelet use and increasing PPI prescribing in patients who require continued antiplatelet therapy. Methods: This study of retrospective chart review included adults (≥18 years) on long-term direct oral anticoagulant (DOAC) therapy from October 2023 to September 2024. The intervention group included AMS-enrolled patients who received structured annual anticoagulation review. The control group consisted of DOAC patients receiving usual care outside AMS. The AMS annual review aims to optimize antithrombotic therapy by deprescribing unnecessary antiplatelets and initiating PPIs when clinically indicated. Results: Of 8,462 eligible patients, 3,125 were in the AMS group and 5,337 in the non-AMS group. Antiplatelet use was significantly lower in AMS patients at baseline (9% vs. 15%) and study end (7% vs. 16%) (p<0.0001). PPI use was significantly higher in AMS patients at both time points (50% vs. 30% for baseline, 67% vs. 38% at the end of study) (p<0.0001). Acceptance rates for AMS recommendations were 18.8% for antiplatelet discontinuation and 33% for PPI initiation. Conclusion: AMS-led interventions effectively reduced concurrent antiplatelet use in patients on background DOAC and increased PPI prescribing in those on dual therapy, demonstrating the value of centralized anticoagulation services in primary care. Direct oral anticoagulants antiplatelet dual antithrombotic therapy triple antithrombotic therapy proton pump inhibitor centralized anticoagulation services Figures Figure 1 Key points Patients on long-term anticoagulation are at increased risk of bleeding when antiplatelets are co-prescribed, highlighting the need for careful medication review via a centralized anticoagulation service (AMS). An AMS-led annual review effectively reduced excessive antiplatelet use in patients on direct oral anticoagulants. AMS interventions increased proton pump inhibitor prescribing for gastric bleeding prophylaxis among patients requiring dual antithrombotic therapy. Further studies are needed to evaluate the clinical outcomes and cost-effectiveness of AMS-led interventions in preventing bleeding while preserving cardiovascular protection. Introduction Patients with atrial fibrillation (AF) and, in some cases, venous thromboembolism require long-term anticoagulation to prevent serious systemic thrombotic complications. For the last decade, anticoagulants have accounted for the highest rate of adverse drug events leading to emergency department visits compared to any other class of medications, with nearly 80% of cases due to hemorrhage [ 1 ]. Many patients with AF and VTE often also have comorbid conditions that are indications for antiplatelet use. For example, half of patients with AF also have coronary artery disease (CAD) and requires careful assessment of antithrombotic regimens [ 2 ]. The addition of single antiplatelet therapy (SAPT) to oral anticoagulation (OAC) increases the risk of nonfatal and fatal bleeding by 2-fold to-3 fold while the addition of dual antiplatelet, known as triple therapy, increases the risk by nearly 4-fold [ 3 ]. Therefore, effective management requires balance between preserving antithrombotic efficacy and minimizing bleeding risk. The benefits of antiplatelet therapy for the prevention of cardiovascular events are well recognized. However, antiplatelet agents should be used with caution in combination with anticoagulants and generally only be reserved for high-risk patients, such as those with recent acute coronary syndrome (ACS) or percutaneous coronary intervention (PCI). In many cases the risks of combining antiplatelet and anticoagulant therapy may outweigh the benefits, particularly in patients who are not at high cardiovascular risk, such as those with stable ischemic heart disease or when being used for primary prevention purposes. In patients with AF undergoing PCI and requiring triple antithrombotic therapy, national and international cardiovascular societies recommend limiting the duration of triple therapy to 1–4 weeks following PCI to minimize bleeding risk [ 4 – 9 ]. This is supported by current evidence indicating that triple therapy after 30 days increases the risk of bleeding without reducing ischemic events [ 10 – 13 ]. For patients with stable CAD and an indication for anticoagulation, current guidelines recommend limiting dual antithrombotic therapy to a maximum duration of 6–12 months following ACS or PCI [ 4 – 9 ]. For those patients who are not at high ischemic risk, duration of clopidogrel may be shortened to 3 months per recommendation from the 2024 ESC guideline [ 7 ]. Data from RCTs and meta-analysis demonstrated that omitting antiplatelet beyond 6 to 12 months after PCI or CABG significantly reduced risk of bleeding without significant difference in ischemic events [ 14 – 16 ]. Despite a paucity of data, some guidelines have extrapolated dual and triple antithrombotic therapy guidance to patients on anticoagulation for other indications such as VTE, and to patients on antiplatelets for alternative indications such as stable peripheral artery disease (PAD) and cerebral vascular disease [ 4 ]. These nuances underscore the importance of individualized risk assessment to mitigate bleeding risk while preserving efficacy in patients at high risk for ischemic cardiovascular disease. Upper gastrointestinal bleeding (UGIB) is the most common major bleeding adverse event associated with combined antiplatelet and anticoagulant use, with a disproportionate increase in rates compared to other types of bleeding [ 17 ]. Unless contraindicated, direct oral anticoagulants (DOACs) are generally preferred over warfarin given the lower risk of intracranial hemorrhage and practical advantages. However, the use of DOACs is associated with an increased risk of UGIB compared to warfarin as shown in pivotal trials for non-valvular atrial fibrillation (NVAF), with apixaban being the only exception [ 18 – 21 ]. These findings highlight the importance of gastroprotection strategies in patients receiving combined antithrombotic therapy. Proton pump inhibitors (PPIs) have been shown in cohort studies to reduce the incidence of UGIB when used during treatment with warfarin or DOACs in patients with high risk of bleeding, [ 22 , 23 ] and are recommended by national cardiovascular and gastroenterology societies for patients receiving dual antithrombotic therapy [ 24 , 25 ]. Histamine-2 receptor antagonists (H2RAs) modestly reduce the risk of UGIB in patients on antithrombotic therapy compared to placebo and remain a reasonable alternative to PPI [ 25 ]. Based on current evidence and guidance from leading professional societies, the Atrius Health Anticoagulation Management Services (AMS) developed internal guidelines and practice protocols to guide management of antithrombotic therapy, including identifying and intervening on excessive antiplatelet use and the addition of a PPI for gastric bleeding prophylaxis for patients that require combined therapy. Continued use of H2RA was allowed if use was stable at baseline. In October 2023, AMS launched an initiative to optimize anticoagulation for all enrollees via an annual comprehensive review of antithrombotic therapy. This review assesses the indication and duration of therapy for anticoagulation, appropriateness of anticoagulant agent, quality of anticoagulation (e.g., warfarin time in target range or medication adherence), co-prescribed antiplatelets, and risk of both thrombosis and bleeding. Any proposed changes to antithrombotic regimens are communicated to the referring physician or care team before implementation. This study aims to evaluate the impact of this initiative on reducing unnecessary antiplatelet use and increasing rates of PPI prescribing for gastroprotection in appropriate patients receiving DOACs within an ambulatory care setting. Methods Study Design This observational study was designed as a retrospective chart review of data from the electronic medical record (EMR). The study was approved by the Institutional Review Boards at Massachusetts College of Pharmacy and Health Sciences and Atrius Health (Approval Number 2024202527) with a waiver of informed consent. Patients were included if they were 18 or older with documented long-term DOAC use from October 2023 to September 2024. The treatment group (“the AMS group”) consisted of patients managed under collaborative drug therapy management (CDTM) and nursing protocols within the centralized Atrius Health AMS who underwent annual review between October 2023 and September 2024. The annual review is a process developed by AMS to optimize antithrombotic therapy, including reducing excess antiplatelet use and increasing PPI use for prevention of UGIB in high-risk patients. The usual care group (“the non-AMS group”) consisted of patients taking DOACs that were not enrolled in AMS and managed instead by their prescribing team. Patients were excluded if they were taking a DOAC for peripheral artery disease or CAD, since these patients require a combination of aspirin 81 mg daily and rivaroxaban 2.5 mg twice daily. Data Collection Patients were identified from the EMR based on the inclusion and exclusion criteria listed above. Baseline data including age, sex, specific DOAC agent and indications for use, specific antiplatelet agent and indications for use, dual antiplatelet use, and PPI or H2RA use were collected (Table 1 ). Use of medications such as DOACs, antiplatelets, PPIs, and H2RAs was determined based on the current medication list at different points in time and their respective start dates and end dates. Medications were considered active at baseline if the start date of the medication order was before October 1, 2023, and the end date was after October 1, 2023 (or if no end date specified). Similarly, end-of-study use of medications was determined if the start date of the medication order was before October 31, 2024. The end-of-study date to capture medication use was extended by one month to allow time for clinician response to AMS recommendations if the annual review was conducted towards the end of September 2024. Outcomes The primary outcome compared the rates of background antiplatelet use and rates of PPI use for gastric prophylaxis in patients on dual antithrombotic therapy between AMS patients who underwent the annual review and non-AMS patients. The secondary outcomes assessed clinician acceptance rates of recommendations made by AMS to discontinue antiplatelets or to start PPIs during the annual review. Statistical Analysis A sample size calculation was performed based on a preliminary review of data in the system, which found that about 13% of the patients enrolled in AMS were using antiplatelets concurrently with DOACs. A minimum sample size of 240, with 120 patients in each of the study groups, would be needed to detect at least a 30% relative decline in antiplatelet use with a power of 80% and an alpha of 0.05. For AMS and non-AMS patients, we separately calculated the frequency of the following variables: sex, baseline DOAC use, indication for DOAC, baseline antiplatelet use, indication for antiplatelet use, and baseline PPI or H2RA use with antiplatelets. A two-sided Fisher’s exact test was used to compare the distribution of these variables between the two groups. Additionally, the mean age and associated standard deviations were calculated for both groups. Means were compared using a two-sample t-test. We calculated the percentage of patients with baseline and end-of-study antiplatelet use for both study groups. Among patients who were taking a concurrent antiplatelet on background DOACs, we calculated the percentage of baseline and end-of-study PPI use in both groups. All these frequencies were compared using Fisher’s exact test. Among patients enrolled in AMS who underwent the annual review, rates of acceptance were calculated using the total number of accepted recommendations and the total number of overall recommendations made during the 2023–2024 annual review for the study populations. For concurrent antiplatelet use, a recommendation can be made to suggest discontinuation of antiplatelets or to recommend reviewing continued antiplatelet use by the prescribing provider. A recommendation is considered accepted if action, including stopping antiplatelets or adding a PPI, is made within 4 weeks of the annual review date. Results Baseline Characteristics Between October 2023 and September 2024, a total of 8,459 patients met all inclusion criteria and were included in the study. A total of 2,748 patients enrolled in AMS did not receive an annual review and were excluded, which could be due to death, disenrollment before annual reviews were due, or being enrolled in AMS within a year of the study end date and thus not due for their first annual review during study period. Patients who were deceased or discharged but had received an annual review were eligible to be included in the study as AMS patients. A total of 47 patients were excluded as they were taking rivaroxaban 2.5 mg twice daily for peripheral artery disease or CAD to reduce risk of cardiovascular events (Fig. 1). As shown in Table 1, more than half of the patients were male, and there was a significant difference in the sex distribution between the AMS and non-AMS groups, (58% in AMS vs. 55% in non-AMS, p=0.0134). Additionally, there was a significant difference in baseline DOAC agent use between groups, with a larger percentage of non-AMS patients taking apixaban (81% vs. 75%) and a larger proportion of AMS patients on rivaroxaban (24% vs. 19%). The overall distribution difference was statistically significant (p<0.0001). The majority of patients were taking a DOAC for NVAF (74% in AMS vs. 67% in non-AMS; p<0.0001 for overall distribution). At baseline, antiplatelet use on a background DOAC differed significantly between the two groups and was higher in the non-AMS group (15% vs. 9%; p<0.0001). No significant difference in dual antiplatelet use was found between the two groups at baseline (1% vs. 3%; p=0.1136). PPI use was significantly higher in the AMS group compared to the non-AMS group among those who were taking both antiplatelets and DOACs at baseline (50% vs. 29%; p<0.0001). H2RA use on antiplatelets did not differ between the two study groups (9% vs. 8%; p=0.9008). Table 1. Baseline Characteristics of Patients* Characteristic AMS group (n=3125) Non-AMS group (n=5334) P-value Sex (%) 0.0134 Female 1317 (42%) 2396 (45%) Male 1808 (58%) 2937 (55%) Age (years) 74.3 ± 11.6 73.4 ± 13.2 0.0016 Range 22-106 18-104 Baseline DOAC use <0.0001 Apixaban 2352 (75%) 4303 (81%) Rivaroxaban 751 (24%) 992 (19%) Dabigatran 20 (1%) 37 (1%) Edoxaban 2 (0%) 2 (0%) Indications for DOAC¥ <0.0001 NVAF 2321 (74%) 3569 (67%) DVT 363 (12%) 478 (9%) PE 367 (12%) 466 (9%) Other VTE 35 (1%) 82 (2%) Other 264 (8%) 1002 (19%) Baseline antiplatelet use 280 (9%) 818 (15%) <0.0001 Aspirin 256 (91%) 728 (89%) Aspirin/dipyridamole 0 (0%) 1 (0%) Clopidogrel 26 (9%) 108 (13%) Prasugrel 0 (0%) 1 (0%) Ticagrelor 1 (0%) 3 (0%) Baseline dual antiplatelet use 3 (1%) 23 (3%) 0.1136 Indications for antiplatelet use¥ 0.0198 CAD or SIHD 163 (58%) 420 (51%) Cerebral vascular disease 126 (45%) 307 (38%) PAD 49 (18%) 116 (14%) Other 72 (26%) 280 (34%) Baseline PPI use for patients on antiplatelet/s 141 (50%) 241 (29%) <0.0001 Baseline H2RA use on antiplatelet 24 (9%) 68 (8%) 0.9008 *NVAF denotes non-valvular atrial fibrillation, DVT deep vein thrombosis, PE pulmonary embolism, VTE venous thromboembolism, STEMI ST elevation myocardial infarction, NSTEMI non-ST elevation myocardial infarction, CAD coronary artery disease, SIHD stable ischemic heart disease, PAD peripheral artery disease. ¥Patient can have multiple concurrent indications for DOAC or antiplatelet use Primary Outcomes The rate of antiplatelet use in the AMS group decreased from 9% to 7% during the study period while the rate in the non-AMS group increased from baseline from 15% to 16% (Table 2). Regardless of the opposing trends in use, antiplatelet use was consistently and significantly higher among the non-AMS group compared to the AMS group throughout the study period (9% vs. 15% for baseline, 7% vs. 16% at the end of study; p<0.0001 for both). End-of-study dual antiplatelet use was numerically higher in the non-AMS group but did not differ significantly compared to the AMS group (4% vs. 3%; p=0.1227). PPI use for patients on dual antithrombotic therapy increased in both groups over time; however, the AMS group had significantly higher rates of PPI use both at baseline (50% vs. 29%; p<0.0001) and at the end of the study (67% vs. 36%; p<0.0001), and also saw a larger relative rate increase over time (34% increase compared to a 20% increase in the non-AMS group). Table 2. Antiplatelet and PPI use at baseline and study end AMS N (%) Non-AMS N (%) P-value Antiplatelet use Baseline antiplatelet use 280 (9%) 818 (15%) <0.0001 End-of-study antiplatelet use 231 (7%) 867 (16%) <0.0001 End-of-study dual antiplatelet use* 5 (2%) 32 (4%) 0.1227 PPI use in patients on dual antithrombotic therapy Baseline PPI use 141 (50%) 241 (29%) <0.0001 End-of-study PPI use 154 (67%) 315 (36%) <0.0001 *Percentage calculated among total antiplatelet users at study end Secondary Outcomes AMS made a total of 308 recommendations to clinicians to deprescribe antiplatelets during the annual review, of which 18.8% (or 58) were accepted (Table 3). Among 79 recommendations to initiate PPIs in patients on dual antithrombotic therapy, 33% (or 26) were accepted, as evidenced by PPI initiation within four weeks of the annual review date. Twenty-five patients received omeprazole while only one received pantoprazole for gastric prophylaxis as a result. Table 3. Antiplatelet and PPI acceptance rate in AMS group Total recommendations made (n) Total accepted recommendations (n) Acceptance rate (%) Deprescribing antiplatelet 308 58 18.8% Adding PPI 79 26 32.9% Discussion The results of this study showed that concurrent antiplatelet use was reduced at end of study in the AMS group while usage increased in the usual care group. PPI use in patients on both antiplatelet and anticoagulant agents increased in both groups at the end of the study, but the AMS group saw a greater increase compared to usual care. The AMS group has significantly lower concurrent antiplatelet use and significantly greater PPI use for UGIB prophylaxis compared to the non-AMS group both at baseline and at the end of the study. The difference in concurrent antiplatelet use at baseline between AMS and non-AMS patients can be attributed to the systematic approach the AMS team employs to optimize DOAC management. Patients managed by AMS undergo a standardized process the time of enrollment that includes a clinical review of their anticoagulation and related therapies, along with periodic outreach to support safe and effective use through monitoring, education, and ad hoc interventions. For the secondary outcome, the total number of recommendations made to deprescribe antiplatelets is higher than the number of patients on antiplatelets at baseline and study end. The study only captured concurrent antiplatelet use at the beginning and end of the study period. As a result, patients who started antiplatelet therapy in either arm during the study period were not captured but could still have received recommendations to deprescribe antiplatelets. The results of our study are similar to prior studies that evaluate the impact of a pharmacist-led protocol or initiative on deprescribing potentially inappropriate antiplatelet use in patients taking long-term anticoagulation. Meador et al. reported the success of a systematic antithrombosis stewardship intervention led by pharmacists in deprescribing concomitant antiplatelet in an outpatient anticoagulation clinic system in Albuquerque, New Mexico [ 26 ]. The de-escalation protocol allowed pharmacists to discontinue antiplatelet therapy or communicate with providers to further discuss discontinuation. The result was 45 (93%) discontinuations among patients whose use was deemed inappropriate, or a total antiplatelet use declined from 30% to 25% among the total of 875 participants who were taking anticoagulant long-term. Another similar study was conducted to assess the effectiveness of pharmacist-led quality improvement initiative in an outpatient anticoagulation clinic of a community hospital located in Toledo, Ohio [ 27 ]. This study also reported 33% concurrent aspirin use at baseline. The initiative successfully identified 22 patients whose aspirin use was deemed inappropriate and reported an acceptance rate of 45% when aspirin deprescribing was recommended to clinicians. A quality improvement observational study conducted in six outpatient anticoagulation clinics in Michigan demonstrated reduction in major bleeding events when aspirin was deprescribed among patients on warfarin for AF and/or VTE (0.31% vs. 0.21%, p = 0.03 for difference in slope before and after the intervention) [ 28 ]. A 2025 meta-analysis by Rashedi et al. pooled efficacy and safety outcomes from four RCTs including patients with AF receiving OAC with or without concomitant antiplatelet therapy [ 16 ]. Included patients were at least 6 months post-PCI or CABG for stable CAD or at least 1 year post-PCI or CABG for ACS. The results demonstrated a significant reduction in major bleeding with OAC monotherapy compared to OAC plus SAPT (3.3% vs. 5.7%; HR: 0.59; 95% CI: 0.44–0.79; p < 0.001; I 2 = 0%). OAC monotherapy was also associated with a lower risk of major or clinically relevant nonmajor bleeding (10.0% vs. 18.4%; HR: 0.53; 95% CI: 0.44–0.63; p < 0.001; I 2 = 58%) based on data from three of the included trials. A major difference in our study design is that these studies did not compare rates of use to a control group receiving usual care along with major differences in baseline antiplatelet use. Overall, the rates of concurrent antiplatelet use in our population, regardless of AMS enrollment status, were substantially lower than those reported in the three studies above. This difference may reflect institution-specific prescribing patterns, increased adherence to current evidence-based guidelines, or a broader downward trend in combined antiplatelet and anticoagulant therapy over time [ 29 ]. Additionally, aspirin is available over-the-counter, its use may have been underreported in the non-AMS group, where no formal verification process existed, unlike the AMS group where it is standard practice to inquire about antiplatelet use on enrollment and document on the medication list. The low rates of antiplatelet use in the AMS group likely reflects formal antiplatelet use guidance developed by AMS and standard antiplatelet use assessments that were completed on enrollment prior to the start of the study period. Similarly, gastroprotective measures are assessed at AMS enrollment and since AMS only recommends PPIs, this process likely contributed to the higher PPI use observed at the start of the study period compared to the non-AMS group while the rates of H2RA use were similar. It is AMS practice to coordinate non-anticoagulant clinical decisions, such as stopping antiplatelets or prescribing PPIs, with key stakeholders in the patients care and therefore we require consultation with the primary care provider and/or specialist prior to enacting these changes. The acceptance rate of antiplatelet deprescribing in our study was lower than that reported in prior studies [ 26 – 28 ]. Since it is standard for AMS to address antiplatelet use on enrollment, subsequent deprescribing decisions may have involved more nuanced clinical judgement and led to the modest acceptance rates seen in the AMS group. Our recommendations are informed by internal guidelines and protocols, which closely align with national guidelines that support deprescribing antiplatelets in patients with stable CAD after one year and adding a gastric prophylaxis agent for high-risk patients. However, some providers may be more cautious about adopting guideline recommendations to stop antiplatelets, particularly in patients with higher risk for recurrent cardiovascular events such as stent thrombosis. While national cardiovascular society guidelines recommend limiting dual antithrombotic therapy to one year in most patients, they also emphasize an individualized approach to antithrombotic management and advise shared decision-making with consideration of patient-specific bleeding and thrombotic risk. For patients with high ischemic risk, such as those with complex coronary lesions, extensive atherosclerosis, or recurrent ischemic events, continuation of antiplatelet may be justified especially when bleeding risk is low. Although we did not assess the clinical outcomes of ischemic or bleeding events, the increased bleeding risk associated with dual or triple therapy and the protective benefits of PPIs against UGIB are well-established in the literature [ 4 – 9 , 14 – 16 , 18 – 21 ]. Furthermore, aspirin deprescribing initiatives have proven to reduce the rates of bleeding in anticoagulated patients [ 28 ]. This study has several limitations. First, the results of our study may be understated as medication use data for the non-AMS group were collected solely based on electronic medical records and were not confirmed through patient interviews, as was done in the study by Medor et al [ 26 ]. Since antiplatelet use, particularly over-the-counter aspirin, was not confirmed in the non-AMS group, actual use may have been higher than reported, which could further increase the difference observed between the usual care and AMS groups. Second, this study only evaluated the impact of the annual review initiative when it was first launched in 2023, and the AMS group only included patients enrolled in AMS for at least 1 year prior to the end of the study period who underwent the 2023–2024 annual review. Patients who were enrolled in AMS after October 2023 had not yet received an annual review and were excluded, even though recommendations to stop unnecessary antiplatelets and initiate PPIs for UGIB prophylaxis could still have been made during enrollment or as part of routine AMS care. Finally, this study was conducted among a cohort of patients from a single ambulatory care organization in Massachusetts and results may not be generalizable to a broader population. Conclusion The AMS intervention was effective in lowering antiplatelet use among patients on DOAC and increasing prescribing rates of PPIs among patients on dual antithrombotic therapy compared to usual care. Despite modest acceptance rates of AMS recommendations during the intervention study period, the overall prescribing rates of antiplatelets and gastric bleeding prophylaxis highlight one of the many valuable roles a centralized AMS can have in optimizing antithrombotic therapy within a primary care setting. This quality initiative is one of several systematic approaches employed by AMS to reduce bleeding and thrombotic events in patients taking DOACs. In addition, AMS responsibilities include maintaining up-to-date lab monitoring, ensuring timely dose adjustments, managing perioperative anticoagulation, providing patient education, addressing drug-drug interaction, facilitating transitions of care, monitoring adherence, and selecting cost-effective, clinically appropriate anticoagulant agents. Further research is needed to confirm the effectiveness of these initiatives in preventing bleeding while preserving cardiovascular protection. Declarations Indications of conflict of interest: The authors declare no conflicts of interest or financial interests in any product or service mentioned in this article, including grants, employment, gifts, stock holdings, or honoraria. Indication of any financial support: The authors declare no financial support or service mentioned in this article, including grants, employment, gifts, stock holdings, or honoraria. Funding: The author(s) received no financial support for the research, authorship, and/or publication of this article. Author Contribution C.H. prepared Figures 1 and Tables 1–3 from the raw data and drafted the main manuscript. D.H. performed the statistical analyses based on the collected and analyzed data. P.C., D.D., and E.M., K.Z. jointly supervised the study. All authors had full access to the raw, unprocessed data and reviewed the final manuscript. Acknowledgement Luis Carpio, MBA, Data Consultant is acknowledged for providing data support. 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J Am Coll Cardiol 85(11):1189-1203. doi:10.1016/j.jacc.2024.12.030 Holster IL, Valkhoff VE, Kuipers EJ, Tjwa ETTL (2013) New oral anticoagulants increase risk for gastrointestinal bleeding: a systematic review and meta-analysis. Gastroenterology 145(1):105-112.e15. doi:10.1053/j.gastro.2013.02.041 Granger CB, Alexander JH, McMurray JJ et al (2011) Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med 365(11):981-992. doi:10.1056/NEJMoa1107039 Patel MR, Mahaffey KW, Garg J et al (2011) Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 365(10):883-891. doi:10.1056/NEJMoa1009638 Connolly SJ, Ezekowitz MD, Yusuf S et al (2009) Dabigatran versus warfarin in patients with atrial fibrillation [published correction appears in N Engl J Med. 2010 Nov 4;363(19):1877]. N Engl J Med 361(12):1139-1151. doi:10.1056/NEJMoa0905561 Giugliano RP, Ruff CT, Braunwald E et al (2013) Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med 369(22):2093-2104. doi:10.1056/NEJMoa1310907 Komen J, Pottegård A, Hjemdahl P et al (2022) Non-vitamin K antagonist oral anticoagulants, proton pump inhibitors and gastrointestinal bleeds. Heart 108(8):613-618. doi:10.1136/heartjnl-2021-319332 Ray WA, Chung CP, Murray KT et al (2018) Association of Oral Anticoagulants and Proton Pump Inhibitor Cotherapy With Hospitalization for Upper Gastrointestinal Tract Bleeding. JAMA 320(21):2221-2230. doi:10.1001/jama.2018.17242 Levine GN, Bates ER, Bittl JA et al (2016) 2016 ACC/AHA guideline Focused Update on duration of Dual Antiplatelet therapy in patients with coronary artery disease. J Am Coll Cardiol 68(10):1082. doi:10.1161/CIR.0000000000000404 Abraham NS, Hlatky MA, Antman EM et al (2010) ACCF/ACG/AHA 2010 Expert Consensus Document on the concomitant use of proton pump inhibitors and thienopyridines: a focused update of the ACCF/ACG/AHA 2008 expert consensus document on reducing the gastrointestinal risks of antiplatelet therapy and NSAID use: a report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents. Circulation 122(24):2619-2633. doi:10.1161/CIR.0b013e318202f701 Meador S, Dyke S, Togami J, Kuskov B, Burnett AE (2022) Antithrombosis stewardship efforts to de-escalate inappropriate combined therapy in outpatient clinics. J Thromb Thrombolysis 53(2):436-445. doi:10.1007/s11239-021-02551-y Domaleczny BJ, Lewis SJ, Richardson JL, Eid HR (2022) Impact of pharmacist intervention to deprescribe inappropriate aspirin therapy in an outpatient anticoagulation clinic at a community hospital. Am Heart J Plus 17:100165. doi:10.1016/j.ahjo.2022.100165 Schaefer JK, Errickson J, Gu X et al (2022) Assessment of an Intervention to Reduce Aspirin Prescribing for Patients Receiving Warfarin for Anticoagulation. JAMA Netw Open 5(9):e2231973. doi:10.1001/jamanetworkopen.2022.31973 Philippe E, Henrard S, Boland B, Marien S (2023) Inappropriate Combined Antiplatelet and Anticoagulant Therapy in Older Patients with Atrial Fibrillation: Trend over Time (2009-18). Drugs Aging 40(3):273-283. doi:10.1007/s40266-023-01006-8 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 29 Apr, 2026 Read the published version in Journal of Thrombosis and Thrombolysis → 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. 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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-8081005","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":549103967,"identity":"9b5fc23f-9c73-41f6-a3c6-27446fb33330","order_by":0,"name":"Chau 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10:09:15","extension":"html","order_by":5,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":113446,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-8081005/v1/16c32935eca37cc88373648f.html"},{"id":96652733,"identity":"f0dc7035-51f9-4548-ac91-0dcdc47c4cfb","added_by":"auto","created_at":"2025-11-24 16:35:25","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":48466,"visible":true,"origin":"","legend":"\u003cp\u003ePatient flow diagram\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-8081005/v1/e0745958b5995bd275068f03.png"},{"id":108437584,"identity":"4c5755f9-c3c3-428b-b332-b941236dcd34","added_by":"auto","created_at":"2026-05-04 15:59:40","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":320535,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8081005/v1/de0f9f83-64de-47b7-854e-77bdef878f26.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003e\u003cstrong\u003eImpact of an Anticoagulation Management Service-led Intervention on Rates of Antiplatelet and Gastric Bleeding Prophylaxis Use in Ambulatory Care Patients on Background Direct Oral Anticoagulants\u003c/strong\u003e\u003c/p\u003e","fulltext":[{"header":"Key points","content":"\u003cul\u003e\n \u003cli\u003ePatients on long-term anticoagulation are at increased risk of bleeding when antiplatelets are co-prescribed, highlighting the need for careful medication review via a centralized anticoagulation service (AMS).\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eAn AMS-led annual review effectively reduced excessive antiplatelet use in patients on direct oral anticoagulants.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eAMS interventions increased proton pump inhibitor prescribing for gastric bleeding prophylaxis among patients requiring dual antithrombotic therapy.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eFurther studies are needed to evaluate the clinical outcomes and cost-effectiveness of AMS-led interventions in preventing bleeding while preserving cardiovascular protection.\u003c/li\u003e\n\u003c/ul\u003e"},{"header":"Introduction","content":"\u003cp\u003ePatients with atrial fibrillation (AF) and, in some cases, venous thromboembolism require long-term anticoagulation to prevent serious systemic thrombotic complications. For the last decade, anticoagulants have accounted for the highest rate of adverse drug events leading to emergency department visits compared to any other class of medications, with nearly 80% of cases due to hemorrhage [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Many patients with AF and VTE often also have comorbid conditions that are indications for antiplatelet use. For example, half of patients with AF also have coronary artery disease (CAD) and requires careful assessment of antithrombotic regimens [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. The addition of single antiplatelet therapy (SAPT) to oral anticoagulation (OAC) increases the risk of nonfatal and fatal bleeding by 2-fold to-3 fold while the addition of dual antiplatelet, known as triple therapy, increases the risk by nearly 4-fold [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Therefore, effective management requires balance between preserving antithrombotic efficacy and minimizing bleeding risk.\u003c/p\u003e\u003cp\u003eThe benefits of antiplatelet therapy for the prevention of cardiovascular events are well recognized. However, antiplatelet agents should be used with caution in combination with anticoagulants and generally only be reserved for high-risk patients, such as those with recent acute coronary syndrome (ACS) or percutaneous coronary intervention (PCI). In many cases the risks of combining antiplatelet and anticoagulant therapy may outweigh the benefits, particularly in patients who are not at high cardiovascular risk, such as those with stable ischemic heart disease or when being used for primary prevention purposes. In patients with AF undergoing PCI and requiring triple antithrombotic therapy, national and international cardiovascular societies recommend limiting the duration of triple therapy to 1\u0026ndash;4 weeks following PCI to minimize bleeding risk [\u003cspan additionalcitationids=\"CR5 CR6 CR7 CR8\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. This is supported by current evidence indicating that triple therapy after 30 days increases the risk of bleeding without reducing ischemic events [\u003cspan additionalcitationids=\"CR11 CR12\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. For patients with stable CAD and an indication for anticoagulation, current guidelines recommend limiting dual antithrombotic therapy to a maximum duration of 6\u0026ndash;12 months following ACS or PCI [\u003cspan additionalcitationids=\"CR5 CR6 CR7 CR8\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. For those patients who are not at high ischemic risk, duration of clopidogrel may be shortened to 3 months per recommendation from the 2024 ESC guideline [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Data from RCTs and meta-analysis demonstrated that omitting antiplatelet beyond 6 to 12 months after PCI or CABG significantly reduced risk of bleeding without significant difference in ischemic events [\u003cspan additionalcitationids=\"CR15\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Despite a paucity of data, some guidelines have extrapolated dual and triple antithrombotic therapy guidance to patients on anticoagulation for other indications such as VTE, and to patients on antiplatelets for alternative indications such as stable peripheral artery disease (PAD) and cerebral vascular disease [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. These nuances underscore the importance of individualized risk assessment to mitigate bleeding risk while preserving efficacy in patients at high risk for ischemic cardiovascular disease.\u003c/p\u003e\u003cp\u003eUpper gastrointestinal bleeding (UGIB) is the most common major bleeding adverse event associated with combined antiplatelet and anticoagulant use, with a disproportionate increase in rates compared to other types of bleeding [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Unless contraindicated, direct oral anticoagulants (DOACs) are generally preferred over warfarin given the lower risk of intracranial hemorrhage and practical advantages. However, the use of DOACs is associated with an increased risk of UGIB compared to warfarin as shown in pivotal trials for non-valvular atrial fibrillation (NVAF), with apixaban being the only exception [\u003cspan additionalcitationids=\"CR19 CR20\" citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. These findings highlight the importance of gastroprotection strategies in patients receiving combined antithrombotic therapy. Proton pump inhibitors (PPIs) have been shown in cohort studies to reduce the incidence of UGIB when used during treatment with warfarin or DOACs in patients with high risk of bleeding, [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e] and are recommended by national cardiovascular and gastroenterology societies for patients receiving dual antithrombotic therapy [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. Histamine-2 receptor antagonists (H2RAs) modestly reduce the risk of UGIB in patients on antithrombotic therapy compared to placebo and remain a reasonable alternative to PPI [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e].\u003c/p\u003e\u003cp\u003e Based on current evidence and guidance from leading professional societies, the Atrius Health Anticoagulation Management Services (AMS) developed internal guidelines and practice protocols to guide management of antithrombotic therapy, including identifying and intervening on excessive antiplatelet use and the addition of a PPI for gastric bleeding prophylaxis for patients that require combined therapy. Continued use of H2RA was allowed if use was stable at baseline. In October 2023, AMS launched an initiative to optimize anticoagulation for all enrollees via an annual comprehensive review of antithrombotic therapy. This review assesses the indication and duration of therapy for anticoagulation, appropriateness of anticoagulant agent, quality of anticoagulation (e.g., warfarin time in target range or medication adherence), co-prescribed antiplatelets, and risk of both thrombosis and bleeding. Any proposed changes to antithrombotic regimens are communicated to the referring physician or care team before implementation. This study aims to evaluate the impact of this initiative on reducing unnecessary antiplatelet use and increasing rates of PPI prescribing for gastroprotection in appropriate patients receiving DOACs within an ambulatory care setting.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eStudy Design\u003c/p\u003e\u003cp\u003eThis observational study was designed as a retrospective chart review of data from the electronic medical record (EMR). The study was approved by the Institutional Review Boards at Massachusetts College of Pharmacy and Health Sciences and Atrius Health (Approval Number 2024202527) with a waiver of informed consent. Patients were included if they were 18 or older with documented long-term DOAC use from October 2023 to September 2024. The treatment group (\u0026ldquo;the AMS group\u0026rdquo;) consisted of patients managed under collaborative drug therapy management (CDTM) and nursing protocols within the centralized Atrius Health AMS who underwent annual review between October 2023 and September 2024. The annual review is a process developed by AMS to optimize antithrombotic therapy, including reducing excess antiplatelet use and increasing PPI use for prevention of UGIB in high-risk patients. The usual care group (\u0026ldquo;the non-AMS group\u0026rdquo;) consisted of patients taking DOACs that were not enrolled in AMS and managed instead by their prescribing team. Patients were excluded if they were taking a DOAC for peripheral artery disease or CAD, since these patients require a combination of aspirin 81 mg daily and rivaroxaban 2.5 mg twice daily.\u003c/p\u003e\u003cp\u003eData Collection\u003c/p\u003e\u003cp\u003ePatients were identified from the EMR based on the inclusion and exclusion criteria listed above. Baseline data including age, sex, specific DOAC agent and indications for use, specific antiplatelet agent and indications for use, dual antiplatelet use, and PPI or H2RA use were collected (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Use of medications such as DOACs, antiplatelets, PPIs, and H2RAs was determined based on the current medication list at different points in time and their respective start dates and end dates. Medications were considered active at baseline if the start date of the medication order was before October 1, 2023, and the end date was after October 1, 2023 (or if no end date specified). Similarly, end-of-study use of medications was determined if the start date of the medication order was before October 31, 2024. The end-of-study date to capture medication use was extended by one month to allow time for clinician response to AMS recommendations if the annual review was conducted towards the end of September 2024.\u003c/p\u003e\u003cp\u003eOutcomes\u003c/p\u003e\u003cp\u003eThe primary outcome compared the rates of background antiplatelet use and rates of PPI use for gastric prophylaxis in patients on dual antithrombotic therapy between AMS patients who underwent the annual review and non-AMS patients. The secondary outcomes assessed clinician acceptance rates of recommendations made by AMS to discontinue antiplatelets or to start PPIs during the annual review.\u003c/p\u003e\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eStatistical Analysis\u003c/h2\u003e\u003cp\u003e A sample size calculation was performed based on a preliminary review of data in the system, which found that about 13% of the patients enrolled in AMS were using antiplatelets concurrently with DOACs. A minimum sample size of 240, with 120 patients in each of the study groups, would be needed to detect at least a 30% relative decline in antiplatelet use with a power of 80% and an alpha of 0.05.\u003c/p\u003e\u003cp\u003eFor AMS and non-AMS patients, we separately calculated the frequency of the following variables: sex, baseline DOAC use, indication for DOAC, baseline antiplatelet use, indication for antiplatelet use, and baseline PPI or H2RA use with antiplatelets. A two-sided Fisher\u0026rsquo;s exact test was used to compare the distribution of these variables between the two groups. Additionally, the mean age and associated standard deviations were calculated for both groups. Means were compared using a two-sample t-test.\u003c/p\u003e\u003cp\u003eWe calculated the percentage of patients with baseline and end-of-study antiplatelet use for both study groups. Among patients who were taking a concurrent antiplatelet on background DOACs, we calculated the percentage of baseline and end-of-study PPI use in both groups. All these frequencies were compared using Fisher\u0026rsquo;s exact test.\u003c/p\u003e\u003cp\u003e Among patients enrolled in AMS who underwent the annual review, rates of acceptance were calculated using the total number of accepted recommendations and the total number of overall recommendations made during the 2023\u0026ndash;2024 annual review for the study populations. For concurrent antiplatelet use, a recommendation can be made to suggest discontinuation of antiplatelets or to recommend reviewing continued antiplatelet use by the prescribing provider. A recommendation is considered accepted if action, including stopping antiplatelets or adding a PPI, is made within 4 weeks of the annual review date.\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eBaseline Characteristics\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eBetween October 2023 and September 2024, a total of 8,459 patients met all inclusion criteria and were included in the study. A total of 2,748 patients enrolled in AMS did not receive an annual review and were excluded, which could be due to death, disenrollment before annual reviews were due, or being enrolled in AMS within a year of the study end date and thus not due for their first annual review during study period. Patients who were deceased or discharged but had received an annual review were eligible to be included in the study as AMS patients. A total of 47 patients were excluded as they were taking rivaroxaban 2.5 mg twice daily for peripheral artery disease or CAD to reduce risk of cardiovascular events (Fig. 1).\u003c/p\u003e\n\u003cp\u003eAs shown in Table 1, more than half of the patients were male, and there was a significant difference in the sex distribution between the AMS and non-AMS groups, (58% in AMS vs. 55% in non-AMS, p=0.0134). Additionally, there was a significant difference in baseline DOAC agent use between groups, with a larger percentage of non-AMS patients taking apixaban (81% vs. 75%) and a larger proportion of AMS patients on rivaroxaban (24% vs. 19%). The overall distribution difference was statistically significant (p\u0026lt;0.0001). The majority of patients were taking a DOAC for NVAF (74% in AMS vs. 67% in non-AMS; p\u0026lt;0.0001 for overall distribution). At baseline, antiplatelet use on a background DOAC differed significantly between the two groups and was higher in the non-AMS group (15% vs. 9%; p\u0026lt;0.0001). No significant difference in dual antiplatelet use was found between the two groups at baseline (1% vs. 3%; p=0.1136). PPI use was significantly higher in the AMS group compared to the non-AMS group among those who were taking both antiplatelets and DOACs at baseline (50% vs. 29%; p\u0026lt;0.0001). H2RA use on antiplatelets did not differ between the two study groups (9% vs. 8%; p=0.9008).\u003c/p\u003e\n\u003cp\u003eTable 1. Baseline Characteristics of Patients*\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 218px;\"\u003e\n \u003cp\u003eCharacteristic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 139px;\"\u003e\n \u003cp\u003eAMS group (n=3125)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003eNon-AMS group (n=5334)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003eP-value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 218px;\"\u003e\n \u003cp\u003eSex (%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 139px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e0.0134\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 218px;\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 139px;\"\u003e\n \u003cp\u003e1317 (42%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e2396 (45%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 218px;\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 139px;\"\u003e\n \u003cp\u003e1808 (58%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e2937 (55%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 218px;\"\u003e\n \u003cp\u003eAge (years)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 139px;\"\u003e\n \u003cp\u003e74.3 \u0026plusmn; 11.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e73.4 \u0026plusmn; 13.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e0.0016\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 218px;\"\u003e\n \u003cp\u003eRange\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 139px;\"\u003e\n \u003cp\u003e22-106\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e18-104\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 218px;\"\u003e\n \u003cp\u003eBaseline DOAC use\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 139px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u0026lt;0.0001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 218px;\"\u003e\n \u003cp\u003eApixaban\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 139px;\"\u003e\n \u003cp\u003e2352 (75%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e4303 (81%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 218px;\"\u003e\n \u003cp\u003eRivaroxaban\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 139px;\"\u003e\n \u003cp\u003e751 (24%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e992 (19%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 218px;\"\u003e\n \u003cp\u003eDabigatran\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 139px;\"\u003e\n \u003cp\u003e20 (1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e37 (1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 218px;\"\u003e\n \u003cp\u003eEdoxaban\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 139px;\"\u003e\n \u003cp\u003e2 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e2 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 218px;\"\u003e\n \u003cp\u003eIndications for DOAC\u0026yen;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 139px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u0026lt;0.0001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 218px;\"\u003e\n \u003cp\u003eNVAF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 139px;\"\u003e\n \u003cp\u003e2321 (74%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e3569 (67%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 218px;\"\u003e\n \u003cp\u003eDVT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 139px;\"\u003e\n \u003cp\u003e363 (12%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e478 (9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 218px;\"\u003e\n \u003cp\u003ePE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 139px;\"\u003e\n \u003cp\u003e367 (12%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e466 (9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 218px;\"\u003e\n \u003cp\u003eOther VTE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 139px;\"\u003e\n \u003cp\u003e35 (1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e82 (2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 218px;\"\u003e\n \u003cp\u003eOther\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 139px;\"\u003e\n \u003cp\u003e264 (8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e1002 (19%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 218px;\"\u003e\n \u003cp\u003eBaseline antiplatelet use\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 139px;\"\u003e\n \u003cp\u003e280 (9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e818 (15%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u0026lt;0.0001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 218px;\"\u003e\n \u003cp\u003eAspirin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 139px;\"\u003e\n \u003cp\u003e256 (91%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e728 (89%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 218px;\"\u003e\n \u003cp\u003eAspirin/dipyridamole\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 139px;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e1 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 218px;\"\u003e\n \u003cp\u003eClopidogrel\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 139px;\"\u003e\n \u003cp\u003e26 (9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e108 (13%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 218px;\"\u003e\n \u003cp\u003ePrasugrel\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 139px;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e1 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 218px;\"\u003e\n \u003cp\u003eTicagrelor\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 139px;\"\u003e\n \u003cp\u003e1 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e3 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 218px;\"\u003e\n \u003cp\u003eBaseline dual antiplatelet use\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 139px;\"\u003e\n \u003cp\u003e3 (1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e23 (3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e0.1136\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 218px;\"\u003e\n \u003cp\u003eIndications for antiplatelet use\u0026yen;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 139px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e0.0198\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 218px;\"\u003e\n \u003cp\u003eCAD or SIHD\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 139px;\"\u003e\n \u003cp\u003e163 (58%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e420 (51%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 218px;\"\u003e\n \u003cp\u003eCerebral vascular disease\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 139px;\"\u003e\n \u003cp\u003e126 (45%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e307 (38%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 218px;\"\u003e\n \u003cp\u003ePAD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 139px;\"\u003e\n \u003cp\u003e49 (18%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e116 (14%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 218px;\"\u003e\n \u003cp\u003eOther\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 139px;\"\u003e\n \u003cp\u003e72 (26%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e280 (34%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 218px;\"\u003e\n \u003cp\u003eBaseline PPI use for patients on antiplatelet/s\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 139px;\"\u003e\n \u003cp\u003e141 (50%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e241 (29%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u0026lt;0.0001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 218px;\"\u003e\n \u003cp\u003eBaseline H2RA use on antiplatelet\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 139px;\"\u003e\n \u003cp\u003e24 (9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e68 (8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e0.9008\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e*NVAF denotes non-valvular atrial fibrillation, DVT deep vein thrombosis, PE pulmonary embolism, VTE venous thromboembolism, STEMI ST elevation myocardial infarction, NSTEMI non-ST elevation myocardial infarction, CAD coronary artery disease, SIHD stable ischemic heart disease, PAD peripheral artery disease.\u003c/p\u003e\n\u003cp\u003e\u0026yen;Patient can have multiple concurrent indications for DOAC or antiplatelet use\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePrimary Outcomes\u003c/p\u003e\n\u003cp\u003eThe rate of antiplatelet use in the AMS group decreased from 9% to 7% during the study period while the rate in the non-AMS group increased from baseline from 15% to 16% (Table 2). Regardless of the opposing trends in use, antiplatelet use was consistently and significantly higher among the non-AMS group compared to the AMS group throughout the study period (9% vs. 15% for baseline, 7% vs. 16% at the end of study;\u0026nbsp;p\u0026lt;0.0001 for both). End-of-study dual antiplatelet use was numerically higher in the non-AMS group but did not differ significantly compared to the AMS group (4% vs. 3%; p=0.1227). PPI use for patients on dual antithrombotic therapy increased in both groups over time; however, the AMS group had significantly higher rates of PPI use both at baseline (50% vs. 29%; p\u0026lt;0.0001) and at the end of the study (67% vs. 36%; p\u0026lt;0.0001), and also saw a larger relative rate increase over time (34% increase compared to a 20% increase in the non-AMS group).\u003c/p\u003e\n\u003cp\u003eTable 2. Antiplatelet and PPI use at baseline and study end\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003eAMS\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eN (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003eNon-AMS\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eN (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003eP-value\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" valign=\"top\" style=\"width: 623px;\"\u003e\n \u003cp\u003eAntiplatelet use\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003eBaseline antiplatelet use\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003e280 (9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003e818 (15%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003e\u0026lt;0.0001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003eEnd-of-study antiplatelet use\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003e231 (7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003e867 (16%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003e\u0026lt;0.0001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003eEnd-of-study dual antiplatelet use*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003e5 (2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003e32 (4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003e0.1227\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" valign=\"top\" style=\"width: 623px;\"\u003e\n \u003cp\u003ePPI use in patients on dual antithrombotic therapy\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003eBaseline PPI use\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003e141 (50%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003e241 (29%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003e\u0026lt;0.0001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003eEnd-of-study PPI use\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003e154 (67%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003e315 (36%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003e\u0026lt;0.0001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e*Percentage calculated among total antiplatelet users at study end\u003c/p\u003e\n\u003cp\u003eSecondary Outcomes\u003c/p\u003e\n\u003cp\u003eAMS made a total of 308 recommendations to clinicians to deprescribe antiplatelets during the annual review, of which 18.8% (or 58) were accepted (Table 3). Among 79 recommendations to initiate PPIs in patients on dual antithrombotic therapy, 33% (or 26) were accepted, as evidenced by PPI initiation within four weeks of the annual review date. Twenty-five patients received omeprazole while only one received pantoprazole for gastric prophylaxis as a result.\u003c/p\u003e\n\u003cp\u003eTable 3. Antiplatelet and PPI acceptance rate in AMS group\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003eTotal recommendations made (n)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003eTotal accepted recommendations (n)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003eAcceptance rate (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003eDeprescribing antiplatelet\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003e308\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003e58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003e18.8%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003eAdding PPI\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003e79\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003e26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003e32.9%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe results of this study showed that concurrent antiplatelet use was reduced at end of study in the AMS group while usage increased in the usual care group. PPI use in patients on both antiplatelet and anticoagulant agents increased in both groups at the end of the study, but the AMS group saw a greater increase compared to usual care. The AMS group has significantly lower concurrent antiplatelet use and significantly greater PPI use for UGIB prophylaxis compared to the non-AMS group both at baseline and at the end of the study.\u003c/p\u003e\u003cp\u003eThe difference in concurrent antiplatelet use at baseline between AMS and non-AMS patients can be attributed to the systematic approach the AMS team employs to optimize DOAC management. Patients managed by AMS undergo a standardized process the time of enrollment that includes a clinical review of their anticoagulation and related therapies, along with periodic outreach to support safe and effective use through monitoring, education, and ad hoc interventions. For the secondary outcome, the total number of recommendations made to deprescribe antiplatelets is higher than the number of patients on antiplatelets at baseline and study end. The study only captured concurrent antiplatelet use at the beginning and end of the study period. As a result, patients who started antiplatelet therapy in either arm during the study period were not captured but could still have received recommendations to deprescribe antiplatelets.\u003c/p\u003e\u003cp\u003eThe results of our study are similar to prior studies that evaluate the impact of a pharmacist-led protocol or initiative on deprescribing potentially inappropriate antiplatelet use in patients taking long-term anticoagulation. Meador et al. reported the success of a systematic antithrombosis stewardship intervention led by pharmacists in deprescribing concomitant antiplatelet in an outpatient anticoagulation clinic system in Albuquerque, New Mexico [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. The de-escalation protocol allowed pharmacists to discontinue antiplatelet therapy or communicate with providers to further discuss discontinuation. The result was 45 (93%) discontinuations among patients whose use was deemed inappropriate, or a total antiplatelet use declined from 30% to 25% among the total of 875 participants who were taking anticoagulant long-term. Another similar study was conducted to assess the effectiveness of pharmacist-led quality improvement initiative in an outpatient anticoagulation clinic of a community hospital located in Toledo, Ohio [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. This study also reported 33% concurrent aspirin use at baseline. The initiative successfully identified 22 patients whose aspirin use was deemed inappropriate and reported an acceptance rate of 45% when aspirin deprescribing was recommended to clinicians. A quality improvement observational study conducted in six outpatient anticoagulation clinics in Michigan demonstrated reduction in major bleeding events when aspirin was deprescribed among patients on warfarin for AF and/or VTE (0.31% vs. 0.21%, p\u0026thinsp;=\u0026thinsp;0.03 for difference in slope before and after the intervention) [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. A 2025 meta-analysis by Rashedi et al. pooled efficacy and safety outcomes from four RCTs including patients with AF receiving OAC with or without concomitant antiplatelet therapy [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Included patients were at least 6 months post-PCI or CABG for stable CAD or at least 1 year post-PCI or CABG for ACS. The results demonstrated a significant reduction in major bleeding with OAC monotherapy compared to OAC plus SAPT (3.3% vs. 5.7%; HR: 0.59; 95% CI: 0.44\u0026ndash;0.79; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001; I\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0%). OAC monotherapy was also associated with a lower risk of major or clinically relevant nonmajor bleeding (10.0% vs. 18.4%; HR: 0.53; 95% CI: 0.44\u0026ndash;0.63; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001; I\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;58%) based on data from three of the included trials.\u003c/p\u003e\u003cp\u003eA major difference in our study design is that these studies did not compare rates of use to a control group receiving usual care along with major differences in baseline antiplatelet use. Overall, the rates of concurrent antiplatelet use in our population, regardless of AMS enrollment status, were substantially lower than those reported in the three studies above. This difference may reflect institution-specific prescribing patterns, increased adherence to current evidence-based guidelines, or a broader downward trend in combined antiplatelet and anticoagulant therapy over time [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. Additionally, aspirin is available over-the-counter, its use may have been underreported in the non-AMS group, where no formal verification process existed, unlike the AMS group where it is standard practice to inquire about antiplatelet use on enrollment and document on the medication list. The low rates of antiplatelet use in the AMS group likely reflects formal antiplatelet use guidance developed by AMS and standard antiplatelet use assessments that were completed on enrollment prior to the start of the study period. Similarly, gastroprotective measures are assessed at AMS enrollment and since AMS only recommends PPIs, this process likely contributed to the higher PPI use observed at the start of the study period compared to the non-AMS group while the rates of H2RA use were similar.\u003c/p\u003e\u003cp\u003eIt is AMS practice to coordinate non-anticoagulant clinical decisions, such as stopping antiplatelets or prescribing PPIs, with key stakeholders in the patients care and therefore we require consultation with the primary care provider and/or specialist prior to enacting these changes. The acceptance rate of antiplatelet deprescribing in our study was lower than that reported in prior studies [\u003cspan additionalcitationids=\"CR27\" citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. Since it is standard for AMS to address antiplatelet use on enrollment, subsequent deprescribing decisions may have involved more nuanced clinical judgement and led to the modest acceptance rates seen in the AMS group. Our recommendations are informed by internal guidelines and protocols, which closely align with national guidelines that support deprescribing antiplatelets in patients with stable CAD after one year and adding a gastric prophylaxis agent for high-risk patients. However, some providers may be more cautious about adopting guideline recommendations to stop antiplatelets, particularly in patients with higher risk for recurrent cardiovascular events such as stent thrombosis. While national cardiovascular society guidelines recommend limiting dual antithrombotic therapy to one year in most patients, they also emphasize an individualized approach to antithrombotic management and advise shared decision-making with consideration of patient-specific bleeding and thrombotic risk. For patients with high ischemic risk, such as those with complex coronary lesions, extensive atherosclerosis, or recurrent ischemic events, continuation of antiplatelet may be justified especially when bleeding risk is low. Although we did not assess the clinical outcomes of ischemic or bleeding events, the increased bleeding risk associated with dual or triple therapy and the protective benefits of PPIs against UGIB are well-established in the literature [\u003cspan additionalcitationids=\"CR5 CR6 CR7 CR8\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan additionalcitationids=\"CR15\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan additionalcitationids=\"CR19 CR20\" citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Furthermore, aspirin deprescribing initiatives have proven to reduce the rates of bleeding in anticoagulated patients [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThis study has several limitations. First, the results of our study may be understated as medication use data for the non-AMS group were collected solely based on electronic medical records and were not confirmed through patient interviews, as was done in the study by Medor et al [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. Since antiplatelet use, particularly over-the-counter aspirin, was not confirmed in the non-AMS group, actual use may have been higher than reported, which could further increase the difference observed between the usual care and AMS groups. Second, this study only evaluated the impact of the annual review initiative when it was first launched in 2023, and the AMS group only included patients enrolled in AMS for at least 1 year prior to the end of the study period who underwent the 2023\u0026ndash;2024 annual review. Patients who were enrolled in AMS after October 2023 had not yet received an annual review and were excluded, even though recommendations to stop unnecessary antiplatelets and initiate PPIs for UGIB prophylaxis could still have been made during enrollment or as part of routine AMS care. Finally, this study was conducted among a cohort of patients from a single ambulatory care organization in Massachusetts and results may not be generalizable to a broader population.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThe AMS intervention was effective in lowering antiplatelet use among patients on DOAC and increasing prescribing rates of PPIs among patients on dual antithrombotic therapy compared to usual care. Despite modest acceptance rates of AMS recommendations during the intervention study period, the overall prescribing rates of antiplatelets and gastric bleeding prophylaxis highlight one of the many valuable roles a centralized AMS can have in optimizing antithrombotic therapy within a primary care setting.\u003c/p\u003e\u003cp\u003eThis quality initiative is one of several systematic approaches employed by AMS to reduce bleeding and thrombotic events in patients taking DOACs. In addition, AMS responsibilities include maintaining up-to-date lab monitoring, ensuring timely dose adjustments, managing perioperative anticoagulation, providing patient education, addressing drug-drug interaction, facilitating transitions of care, monitoring adherence, and selecting cost-effective, clinically appropriate anticoagulant agents. Further research is needed to confirm the effectiveness of these initiatives in preventing bleeding while preserving cardiovascular protection.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eIndications of conflict of interest:\u003c/h2\u003e\n\u003cp\u003eThe authors declare no conflicts of interest or financial interests in any product or service mentioned in this article, including grants, employment, gifts, stock holdings, or honoraria.\u003c/p\u003e\n\u003ch2\u003eIndication of any financial support:\u003c/h2\u003e\n\u003cp\u003eThe authors declare no financial support or service mentioned in this article, including grants, employment, gifts, stock holdings, or honoraria.\u003c/p\u003e\n\u003ch2\u003eFunding:\u003c/h2\u003e\n\u003cp\u003eThe author(s) received no financial support for the research, authorship, and/or publication of this article.\u003c/p\u003e\n\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\n\u003cp\u003eC.H. prepared Figures 1 and Tables 1\u0026ndash;3 from the raw data and drafted the main manuscript. D.H. performed the statistical analyses based on the collected and analyzed data. P.C., D.D., and E.M., K.Z. jointly supervised the study. All authors had full access to the raw, unprocessed data and reviewed the final manuscript.\u003c/p\u003e\n\u003ch2\u003eAcknowledgement\u003c/h2\u003e\n\u003cp\u003eLuis Carpio, MBA, Data Consultant is acknowledged for providing data support.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eShehab N, Lovegrove MC, Geller AI, Rose KO, Weidle NJ, Budnitz DS (2016) US Emergency Department Visits for Outpatient Adverse Drug Events, 2013-2014. JAMA 316(20):2115-2125. doi:10.1001/jama.2016.16201\u003c/li\u003e\n\u003cli\u003eMichniewicz E, Mlodawska E, Lopatowska P, Tomaszuk-Kazberuk A, Malyszko J (2018) Patients with atrial fibrillation and coronary artery disease - Double trouble. 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Eur Heart J 45(36):3415-3537. doi:10.1093/eurheartj/ehae177\u003c/li\u003e\n\u003cli\u003eLip GYH, Banerjee A, Boriani G et al (2018) Antithrombotic Therapy for Atrial Fibrillation: CHEST Guideline and Expert Panel Report. Chest 154(5):1121-1201. doi:10.1016/j.chest.2018.07.040\u003c/li\u003e\n\u003cli\u003eJoglar JA, Chung MK, Armbruster AL et al (2024) 2023 ACC/AHA/ACCP/HRS Guideline for the Diagnosis and Management of Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation 149(1):e1-e156. doi:10.1161/CIR.0000000000001193\u003c/li\u003e\n\u003cli\u003eDewilde WJ, Oirbans T, Verheugt FW et al (2013) Use of clopidogrel with or without aspirin in patients taking oral anticoagulant therapy and undergoing percutaneous coronary intervention: an open-label, randomised, controlled trial. Lancet 381(9872):1107-1115. doi:10.1016/S0140-6736(12)62177-1\u003c/li\u003e\n\u003cli\u003eCannon CP, Bhatt DL, Oldgren J et al (2017) Dual Antithrombotic Therapy with Dabigatran after PCI in Atrial Fibrillation. N Engl J Med 377(16):1513-1524. doi:10.1056/NEJMoa1708454\u003c/li\u003e\n\u003cli\u003eLopes RD, Heizer G, Aronson R et al (2019) Antithrombotic Therapy after Acute Coronary Syndrome or PCI in Atrial Fibrillation. N Engl J Med 380(16):1509-1524. doi:10.1056/NEJMoa1817083\u003c/li\u003e\n\u003cli\u003ePotpara TS, Mujovic N, Proietti M et al (2020) Revisiting the effects of omitting aspirin in combined antithrombotic therapies for atrial fibrillation and acute coronary syndromes or percutaneous coronary interventions: meta-analysis of pooled data from the PIONEER AF-PCI, RE-DUAL PCI, and AUGUSTUS trials. Europace 22(1):33-46. doi:10.1093/europace/euz259 \u003c/li\u003e\n\u003cli\u003eYasuda S, Kaikita K, Akao M et al (2019) Antithrombotic Therapy for Atrial Fibrillation with Stable Coronary Disease. N Engl J Med 381(12):1103-1113. doi:10.1056/NEJMoa1904143\u003c/li\u003e\n\u003cli\u003eCho MS, Kang DY, Ahn JM et al (2024) Edoxaban Antithrombotic Therapy for Atrial Fibrillation and Stable Coronary Artery Disease. N Engl J Med 391(22):2075-2086. doi:10.1056/NEJMoa2407362\u003c/li\u003e\n\u003cli\u003eRashedi S, Keykhaei M, Sato A et al (2025) Anticoagulation and Antiplatelet Therapy for Atrial Fibrillation and Stable Coronary Disease: Meta-Analysis of Randomized Trials. J Am Coll Cardiol 85(11):1189-1203. doi:10.1016/j.jacc.2024.12.030\u003c/li\u003e\n\u003cli\u003eHolster IL, Valkhoff VE, Kuipers EJ, Tjwa ETTL (2013) New oral anticoagulants increase risk for gastrointestinal bleeding: a systematic review and meta-analysis. Gastroenterology 145(1):105-112.e15. doi:10.1053/j.gastro.2013.02.041\u003c/li\u003e\n\u003cli\u003eGranger CB, Alexander JH, McMurray JJ et al (2011) Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med 365(11):981-992. doi:10.1056/NEJMoa1107039\u003c/li\u003e\n\u003cli\u003ePatel MR, Mahaffey KW, Garg J et al (2011) Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 365(10):883-891. doi:10.1056/NEJMoa1009638\u003c/li\u003e\n\u003cli\u003eConnolly SJ, Ezekowitz MD, Yusuf S et al (2009) Dabigatran versus warfarin in patients with atrial fibrillation [published correction appears in N Engl J Med. 2010 Nov 4;363(19):1877]. N Engl J Med 361(12):1139-1151. doi:10.1056/NEJMoa0905561\u003c/li\u003e\n\u003cli\u003eGiugliano RP, Ruff CT, Braunwald E et al (2013) Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med 369(22):2093-2104. doi:10.1056/NEJMoa1310907\u003c/li\u003e\n\u003cli\u003eKomen J, Potteg\u0026aring;rd A, Hjemdahl P et al (2022) Non-vitamin K antagonist oral anticoagulants, proton pump inhibitors and gastrointestinal bleeds. Heart 108(8):613-618. doi:10.1136/heartjnl-2021-319332\u003c/li\u003e\n\u003cli\u003eRay WA, Chung CP, Murray KT et al (2018) Association of Oral Anticoagulants and Proton Pump Inhibitor Cotherapy With Hospitalization for Upper Gastrointestinal Tract Bleeding. JAMA 320(21):2221-2230. doi:10.1001/jama.2018.17242\u003c/li\u003e\n\u003cli\u003eLevine GN, Bates ER, Bittl JA et al (2016) 2016 ACC/AHA guideline Focused Update on duration of Dual Antiplatelet therapy in patients with coronary artery disease. J Am Coll Cardiol 68(10):1082. doi:10.1161/CIR.0000000000000404\u003c/li\u003e\n\u003cli\u003eAbraham NS, Hlatky MA, Antman EM et al (2010) ACCF/ACG/AHA 2010 Expert Consensus Document on the concomitant use of proton pump inhibitors and thienopyridines: a focused update of the ACCF/ACG/AHA 2008 expert consensus document on reducing the gastrointestinal risks of antiplatelet therapy and NSAID use: a report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents. Circulation 122(24):2619-2633. doi:10.1161/CIR.0b013e318202f701\u003c/li\u003e\n\u003cli\u003eMeador S, Dyke S, Togami J, Kuskov B, Burnett AE (2022) Antithrombosis stewardship efforts to de-escalate inappropriate combined therapy in outpatient clinics. J Thromb Thrombolysis 53(2):436-445. doi:10.1007/s11239-021-02551-y\u003c/li\u003e\n\u003cli\u003eDomaleczny BJ, Lewis SJ, Richardson JL, Eid HR (2022) Impact of pharmacist intervention to deprescribe inappropriate aspirin therapy in an outpatient anticoagulation clinic at a community hospital. Am Heart J Plus\u003cem\u003e \u003c/em\u003e17:100165. doi:10.1016/j.ahjo.2022.100165\u003c/li\u003e\n\u003cli\u003eSchaefer JK, Errickson J, Gu X et al (2022) Assessment of an Intervention to Reduce Aspirin Prescribing for Patients Receiving Warfarin for Anticoagulation. JAMA Netw Open 5(9):e2231973. doi:10.1001/jamanetworkopen.2022.31973\u003c/li\u003e\n\u003cli\u003ePhilippe E, Henrard S, Boland B, Marien S (2023) Inappropriate Combined Antiplatelet and Anticoagulant Therapy in Older Patients with Atrial Fibrillation: Trend over Time (2009-18). Drugs Aging 40(3):273-283. doi:10.1007/s40266-023-01006-8\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"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":"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":"Direct oral anticoagulants, antiplatelet, dual antithrombotic therapy, triple antithrombotic therapy, proton pump inhibitor, centralized anticoagulation services","lastPublishedDoi":"10.21203/rs.3.rs-8081005/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8081005/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePatients on long-term anticoagulation face increased bleeding risk when antiplatelets are co-prescribed, especially upper gastrointestinal (GI) bleeding. Guidelines recommend limiting antiplatelet use to highly select patients on background anticoagulants and promoting GI prophylaxis with proton pump inhibitors (PPIs) for those requiring dual antithrombotic therapy.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eObjectives:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTo assess the impact of an anticoagulation management service (AMS)-led intervention on reducing excess antiplatelet use and increasing PPI prescribing in patients who require continued antiplatelet therapy.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study of retrospective chart review included adults (≥18 years) on long-term direct oral anticoagulant (DOAC) therapy from October 2023 to September 2024. The intervention group included AMS-enrolled patients who received structured annual anticoagulation review. The control group consisted of DOAC patients receiving usual care outside AMS. The AMS annual review aims to optimize antithrombotic therapy by deprescribing unnecessary antiplatelets and initiating PPIs when clinically indicated.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOf 8,462 eligible patients, 3,125 were in the AMS group and 5,337 in the non-AMS group. Antiplatelet use was significantly lower in AMS patients at baseline (9% vs. 15%) and study end (7% vs. 16%) (p\u0026lt;0.0001). PPI use was significantly higher in AMS patients at both time points (50% vs. 30% for baseline, 67% vs. 38% at the end of study) (p\u0026lt;0.0001). Acceptance rates for AMS recommendations were 18.8% for antiplatelet discontinuation and 33% for PPI initiation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAMS-led interventions effectively reduced concurrent antiplatelet use in patients on background DOAC and increased PPI prescribing in those on dual therapy, demonstrating the value of centralized anticoagulation services in primary care.\u003c/p\u003e","manuscriptTitle":"Impact of an Anticoagulation Management Service-led Intervention on Rates of Antiplatelet and Gastric Bleeding Prophylaxis Use in Ambulatory Care Patients on Background Direct Oral Anticoagulants","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-11-24 16:35:21","doi":"10.21203/rs.3.rs-8081005/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":"2ad8dbe4-26b8-400c-a4c5-a87f5171d3c2","owner":[],"postedDate":"November 24th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-05-04T15:59:21+00:00","versionOfRecord":{"articleIdentity":"rs-8081005","link":"https://doi.org/10.1007/s11239-026-03283-7","journal":{"identity":"journal-of-thrombosis-and-thrombolysis","isVorOnly":false,"title":"Journal of Thrombosis and Thrombolysis"},"publishedOn":"2026-04-29 15:57:13","publishedOnDateReadable":"April 29th, 2026"},"versionCreatedAt":"2025-11-24 16:35:21","video":"","vorDoi":"10.1007/s11239-026-03283-7","vorDoiUrl":"https://doi.org/10.1007/s11239-026-03283-7","workflowStages":[]},"version":"v1","identity":"rs-8081005","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8081005","identity":"rs-8081005","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}