Pharmacotherapy最新文献

{"title":"Hereditary Pseudocholinesterase Deficiency and Succinylcholine: Historical Perspective, Therapeutic Implications, and Future Considerations.","authors":"Jenny Q Nguyen, Courtney Paetznick, Roseann S Donnelly","doi":"10.1002/phar.70048","DOIUrl":"10.1002/phar.70048","url":null,"abstract":"<p><p>Succinylcholine, a commonly used neuromuscular blocker, is hydrolyzed by the pseudocholinesterase (also known as butyrylcholinesterase) enzyme in the plasma to inactive metabolites. Individuals who have inherited genetic variants in the BCHE gene that result in decreased or no pseudocholinesterase enzyme activity are at increased risk of prolonged neuromuscular blockade with succinylcholine. Although succinylcholine/BCHE is one of the earliest identified pharmacogenomic drug/gene associations, clinical implementation remains the exception rather than the norm today. This review will explore the historical roots of pseudocholinesterase deficiency, its therapeutic implications for succinylcholine use, and future considerations for BCHE genetic testing to minimize the occurrence of prolonged neuromuscular blockade that can cause serious physical (i.e., apnea) and psychological (i.e., post-traumatic stress) consequences for patients. A summary and critical examination of the published literature that includes BCHE genetic testing in relation to succinylcholine response is also provided. Prolonged paralysis with succinylcholine may be prevented with preemptive BCHE genetic testing.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":"600-620"},"PeriodicalIF":3.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144799913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of P2Y12 Inhibitors on Major Adverse Cardiovascular Events After Coronary Artery Bypass Graft Surgery: A Population-Based Cohort Study.","authors":"Arden R Barry, Hamed Helisaz, Abdollah Safari, Peter S Loewen","doi":"10.1002/phar.70047","DOIUrl":"10.1002/phar.70047","url":null,"abstract":"<p><strong>Background: </strong>Patients who undergo coronary artery bypass graft (CABG) surgery remain at high risk for major adverse cardiovascular events (MACE) despite contemporary preventive pharmacotherapy. Although commonly used in practice, it is uncertain whether P2Y12 inhibitors reduce MACE in patients post-CABG surgery.</p><p><strong>Methods: </strong>This retrospective, population-based cohort study evaluated the effect of exposure to P2Y12 inhibitors, versus no exposure, on MACE using linked administrative databases that included all cardiac revascularization procedures, hospitalizations, and prescriptions for the population of British Columbia, Canada. All adults who underwent CABG surgery from 2002 to 2020 were eligible. The primary outcome was time to MACE, defined as a composite of all-cause death, nonfatal myocardial infarction, and nonfatal ischemic stroke using Cox proportional hazards models with inverse probability treatment weighting.</p><p><strong>Results: </strong>Included were 15,439 patients. Mean age was 66 years, and 83% were male. Fifty-seven percent had a previous myocardial infarction. Sixteen percent were prescribed a P2Y12 inhibitor (of which, 83% were prescribed clopidogrel) within 30 days of CABG surgery. Median exposure time was 23 months. After probability-weighting and adjustment for relevant covariates, exposure to P2Y12 inhibitors reduced the 1- and 5-year hazard of MACE (hazard ratio [HR] 0.39, 95% confidence interval [CI] 0.27-0.55 and HR 0.65, 95% CI 0.54-0.79, respectively). Exposure to P2Y12 inhibitors was also associated with a lower hazard of all-cause death, cardiovascular death, and an extended MACE outcome that included unstable angina and percutaneous coronary intervention. Adherence to P2Y12 inhibitor therapy, based on the proportion of days covered, did not affect these outcomes.</p><p><strong>Conclusions: </strong>In this population-based cohort study, use of P2Y12 inhibitors reduced the hazard of MACE in patients post-CABG surgery at 1 and 5 years of follow-up. These results support the use of P2Y12 inhibitors (primarily clopidogrel), in addition to other standard cardiovascular preventive therapy, in patients who undergo CABG surgery.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":"557-565"},"PeriodicalIF":3.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12424524/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144732732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Drug-Drug Interactions and Combination Therapy Strategies of Amiodarone With Digoxin, Rivaroxaban, and Phenytoin Assessed by Physiologically Based Pharmacokinetic Modeling.","authors":"Youjun Chen, Zhiwei Liu, Yiming Li, Wenhui Wang, Tao Chen, Saiya Li, Yating Wu, Haitang Xie","doi":"10.1002/phar.70050","DOIUrl":"10.1002/phar.70050","url":null,"abstract":"<p><strong>Background: </strong>Amiodarone (AMI) is a potent inhibitor of Cytochrome P450 (CYP) 2C9 and P-glycoprotein (P-gp), as well as a weak inhibitor of CYP3A4. Concomitant administration of AMI with digoxin (DIG), rivaroxaban (RIV), or phenytoin (PHT) can significantly increase the exposure of the victim drugs. Elevated RIV exposure raises the risk of bleeding, whereas DIG and PHT have narrow therapeutic windows, potentially leading to severe toxicity when co-administered with AMI.</p><p><strong>Purpose: </strong>Physiologically based pharmacokinetic (PBPK) modeling was employed to simulate, validate, and predict the impact of drug-drug interactions (DDIs) between AMI and DIG, RIV, or PHT on the pharmacokinetics (PK) of victim drugs. The findings aim to provide evidence-based recommendations for optimizing combination therapy regimens.</p><p><strong>Methods: </strong>PBPK models for AMI, RIV, and PHT were developed using PK-Sim, while the DIG model was adopted from previously published literature. DDI scenarios were simulated to assess exposure levels. Model performance was evaluated by comparing predicted plasma concentration-time (PCT) profiles and PK parameter values with clinical trial data from healthy subjects in previously published PK studies. Finally, dosing regimens for combination therapy were adjusted based on changes in exposure levels.</p><p><strong>Results: </strong>According to model simulations, when the perpetrator drug AMI was co-administered with DIG, RIV, or PHT following label-recommended dosing regimens, the steady-state exposure of the victim drugs increased by 79%, 38%, and 59%, respectively. Compared to monotherapy, reducing the doses of DIG, RIV, and PHT by 40%, 25%, and 45%, respectively, achieved similar steady-state concentrations.</p><p><strong>Conclusions: </strong>We have successfully developed PBPK models for AMI, RIV, and PHT. These models effectively simulate the DDIs that occur when AMI is co-administered with DIG, RIV, or PHT, thereby providing guidance for dosing regimens in clinical combination therapies.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":"566-577"},"PeriodicalIF":3.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144837297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comment on \"Proton Pump Inhibitor Concomitant Use to Prevent Oxaliplatin-Induced Peripheral Neuropathy: Clinical Retrospective Cohort Study\".","authors":"Majid Khalilizad, Ebrahim Hejazian, Mohammad Barary, Amirhossein Zohrevand, Soheil Ebrahimpour","doi":"10.1002/phar.70053","DOIUrl":"10.1002/phar.70053","url":null,"abstract":"","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":"621-622"},"PeriodicalIF":3.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144795071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intraperitoneal Granisetron for Post-Laparoscopic Cholecystectomy Pain Management: A Double-Blinded, Randomized Controlled Trial.","authors":"Hoda Mohamed Bayoumi, Doaa Hamed Abdelaziz, Sherif Boraii, Ehab Rasmy Bendas, Nouran Omar El Said","doi":"10.1002/phar.70046","DOIUrl":"10.1002/phar.70046","url":null,"abstract":"<p><strong>Background: </strong>Laparoscopic cholecystectomy (LC) may cause significant pain, increasing morbidity. Granisetron, an antiemetic selective serotonin (5HT3)-antagonist, demonstrates analgesic properties through sodium channel blockade. The current study aims to assess the efficacy of adjuvant intraperitoneal granisetron in post-LC pain.</p><p><strong>Research design and methods: </strong>In this prospective randomized controlled trial, 48 patients undergoing LC were randomized into placebo (intraperitoneal saline) and intervention (intraperitoneal granisetron) groups. Pain intensity was measured via visual analog scale (VAS) at 2-, 4-, 8-, 12-, and 24-h post-surgery, with comparative analysis of the area under the curve (AUC) of the 24-h VAS scores. Additional outcomes included sedation levels, persistent pain incidence, quality of life improvement, postoperative nausea and vomiting (PONV), time to first rescue analgesic request, total analgesic consumption, and independent mobilization.</p><p><strong>Results: </strong>The treatment group showed significantly lower VAS at 8, 12, and 24 h (p = 0.039, 0.004, 0.030) and lower VAS score AUC (542.7 ± 260.5 vs. 767.1 ± 317.8, p = 0.011) compared to controls, respectively. No significant differences were observed in (2-4 h) pain scores, persistent pain incidence, quality of life, sedation levels, PONV, analgesic requirements, or mobilization time (p < 0.05).</p><p><strong>Conclusions: </strong>Granisetron could improve multimodal pain control after LC, offering better outcomes while maintaining its established safety profile.</p><p><strong>Trial registration: </strong>NCT06281418.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":"547-556"},"PeriodicalIF":3.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144691197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Precision Daptomycin Dosing: Comparison of 3-, 2-, 1-, and 0-Concentration Sample Strategies.","authors":"Simone Giuliano, Manjunath P Pai, Jacopo Angelini, Sarah Flammini, Luca Martini, Massimo Baraldo, Carlo Tascini","doi":"10.1002/phar.70045","DOIUrl":"10.1002/phar.70045","url":null,"abstract":"<p><strong>Background: </strong>Daptomycin is a once-daily lipopeptide antibiotic with a narrow therapeutic window. As higher doses (8-12 mg/kg) are increasingly used to treat resistant gram-positive infections, achieving therapeutic exposure while minimizing toxicity has become critical. Understanding daptomycin therapeutic drug monitoring (TDM) and what sampling strategy may be most precise and feasible are key to guiding appropriate dosing. The primary objective of this study was to ascertain the precision and bias of a mid-point sample area under the curve over 24-h (AUC₂₄) determination compared to a peak and trough sample AUC₂₄ determination using both simple calculation-based methods and a Bayesian model versus no TDM.</p><p><strong>Methods: </strong>Adult patients receiving daptomycin with at least three steady-state concentrations (peak, mid-point, trough) were included in this analysis. A previously published one-compartment population pharmacokinetic model was applied using Bayesian estimation (Monolix Suite 2024R1). AUC₂₄ values were estimated using all three concentrations (AUC_ref), and then re-estimated using individual samples (peak, mid-point, or trough) or paired samples (peak + trough). Performance of each strategy was evaluated using regression analysis with the coefficient of determination for precision (R²) and mean bias.</p><p><strong>Results: </strong>The cohort included 210 patients (60% male) with a mean (range) age of 66 (18-91) years, body weight 78 (41-140) kg, and BMI 27 (14-51) kg/m². A total of 880 daptomycin concentrations were analyzed in patients receiving a mean (range) daptomycin dose of 9 (5-17) mg/kg. The mean (range) AUC₂₄ was 869 (385-1692) mg·h/L; only 45.7% of patients achieved the target range of 666 to 939 mg·h/L. A single mid-point sample had similar correlation to AUC₂₄ (R² = 0.57) as trough-only (R² = 0.55), and greater precision than peak-only (R² = 0.44). Bayesian estimation with two samples (peak + trough) provided the highest accuracy (R² = 0.87) and lowest bias.</p><p><strong>Conclusions: </strong>A mid-interval sampling strategy offers a practical alternative to traditional TDM for daptomycin, enabling more consistent AUC estimation when full sampling is not feasible. A two-sample Bayesian approach remains the most accurate, supporting broader implementation of individualized daptomycin dosing.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":"540-546"},"PeriodicalIF":3.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12424523/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144795072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Trends in Initiation of Disease-Modifying Antirheumatic Drugs for Rheumatoid Arthritis Among Commercially Insured Adults in the United States, 2001-2021.","authors":"Lydia Y Lee, Jeffrey A Sparks, Priyanka Yalamanchili, Daniel B Horton, Zeba M Khan, Joseph Barone, Chintan V Dave","doi":"10.1002/phar.70051","DOIUrl":"10.1002/phar.70051","url":null,"abstract":"<p><strong>Objective: </strong>To evaluate patterns in disease-modifying antirheumatic drugs (DMARDs) initiations between 2001 and 2021 among adults with Rheumatoid Arthritis (RA) in the United States METHODS: This retrospective cohort study used a US commercial claims database (2001-2021) to identify patients (≥ 18 years) with RA newly initiating a DMARD. We calculated the annual proportion of initiations for 22 DMARDs, categorized as conventional synthetic (csDMARDs), biologic (bDMARDs), and targeted synthetic (tsDMARDs). Secondary analyses examined trends in first-line non-csDMARD initiation and biosimilar uptake.</p><p><strong>Results: </strong>We identified 407,728 DMARD initiation episodes among 229,365 unique patients with RA (median age: 50 years [IQR], 44-58 years; 79.4% female). There were shifts in DMARD initiations, with csDMARD initiation declining from 79.9% of initiations in 2001 to 54.7% by 2021 (p < 0.001 for trend). Meanwhile, bDMARDs and tsDMARDs initiations increased from 20.3% in 2001 to 33.1% in 2021 (p < 0.001) and from 0.1% in 2012 to 12.2% in 2021 (p = 0.171), respectively. Methotrexate remained the most initiated DMARD over the 21-year study period, albeit declining from 28.7% to 15.0% of initiations over the study period (p < 0.001). Adalimumab was the most frequently initiated bDMARD (13.3% in 2003 and 12.2% in 2021; p = 0.05). Among tsDMARDs, tofacitinib initiation peaked at 8.9% in 2019 and declined to 4.4% in 2021, while upadacitinib initiation increased from 1.2% to 7.6% during the same period (p < 0.001). For secondary analyses, adalimumab was the predominant first-line b/tsDMARD initiated (> 40%). Biosimilar uptake stayed below 1%.</p><p><strong>Conclusion: </strong>Expanded DMARD options over the last two decades have led to decreased csDMARD initiations and increased b/tsDMARD initiations, reflecting patient- and system-level factors.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":"578-586"},"PeriodicalIF":3.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144822263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Response to Comment on \"Proton Pump Inhibitor Concomitant Use to Prevent Oxaliplatin-Induced Peripheral Neuropathy: Clinical Retrospective Cohort Study\".","authors":"Keisuke Mine, Takehiro Kawashiri, Yusuke Mori, Shunsuke Fujita, Mayako Uchida, Takaaki Yamada, Nobuaki Egashira, Ichiro Ieiri, Satoru Koyanagi, Shigehiro Ohdo, Takao Shimazoe, Daisuke Kobayashi","doi":"10.1002/phar.70054","DOIUrl":"10.1002/phar.70054","url":null,"abstract":"","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":"623-624"},"PeriodicalIF":3.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144795073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biological Therapy and Small Molecules for Adults With Crohn's Disease: Systematic Review and Network Meta-Analysis.","authors":"Daniela Gorski, Raul Edison Luna Lazo, Dalton de Assis de Souza, Helena Hiemisch Lobo Borba, Roberto Pontarolo, Fernanda Stumpf Tonin","doi":"10.1002/phar.70049","DOIUrl":"10.1002/phar.70049","url":null,"abstract":"<p><p>First-line therapeutic approaches for Crohn's disease include immunosuppressants, aminosalicylates, and corticosteroids. However, more than one-third of patients are resistant to these treatments and require second-line therapies. Our goal was to synthesize the evidence on the efficacy and safety of biologics and small molecules for inducing remission in patients with moderate-to-severe Crohn's disease. A systematic review was conducted by searching for randomized controlled trials on the target population in PubMed, Scopus, and Web of Science (March 2025). Data synthesis for the outcomes of remission, health-related quality of life (HRQoL), and safety was performed using network meta-analyses and surface under the cumulative rating curve (SUCRA) analyses. The results were presented as risk ratios with 95% credible intervals. We included 55 trials (n = 16,113 patients) evaluating 26 biological drugs across 83 doses and six small molecules across 15 doses. Similar results were obtained in the sensitivity analyses conducted across different measurement time points. Alongside infliximab 5 mg/kg (SUCRA 98.6%), 10 mg/kg (92%), and 20 mg/kg intravenous (91.8%), the recently approved drugs guselkumab 1200 mg (83.2%), 600 mg (89.2%), and 200 mg intravenous (90.1%), as well as mirikizumab 600 mg (91.5%) and 1000 mg intravenous (82.4%) presented higher probabilities of disease remission and were associated with increased HRQoL. Drugs such as certolizumab, andecaliximab, fontolizumab, abatacept, and etanercept ranked low for remission (SUCRA < 40%) and presented high probabilities of serious adverse events (over 60%). Small molecules presented an intermediate profile. Inhibitors of interleukin-23 appear to be promising alternatives for the treatment of moderate-to-severe Crohn's disease. Given their safety profile, some anti-TNF drugs should be avoided in practice. Trial Registration: PROSPERO: CRD42024519150.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":"587-599"},"PeriodicalIF":3.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12424525/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144795070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Restarting Oral Anticoagulation in Patients With Atrial Fibrillation After Admission for a Gastrointestinal Bleeding Event: Effectiveness and Safety of Direct Oral Anticoagulants Compared to Warfarin.","authors":"Oluwadolapo D Lawal, Herbert D Aronow, Fisayomi Shobayo, Yichi Zhang, Anne L Hume, Tracey H Taveira, Kelly L Matson, Justin Gold, Xuerong Wen","doi":"10.1002/phar.70055","DOIUrl":"https://doi.org/10.1002/phar.70055","url":null,"abstract":"<p><strong>Background: </strong>There are sparse data to guide resumption of direct oral anticoagulants (DOACs) versus warfarin in patients with atrial fibrillation (AF) who survive a major gastrointestinal bleeding (GIB) event.</p><p><strong>Objective: </strong>To compare the risk-benefit profile of restarting DOACs versus warfarin among patients with AF following hospitalization for major GIB.</p><p><strong>Methods: </strong>Using claims submitted to a commercial health insurance database from January 2010 to December 2017, we identified adult patients with AF hospitalized for a major GIB while receiving oral anticoagulants. Eligible patients were required to have survived and restarted oral anticoagulation with DOACs or warfarin within 90 days following hospital discharge for major GIB. The outcomes of interest were subsequent hospitalization for major bleeding, hospitalization for ischemic stroke/systemic embolism (SE), all-cause mortality, and net adverse clinical effect (NACE), which was a composite of all-cause mortality, hospitalization for ischemic stroke/SE, and hospitalization for major bleeding. Stabilized inverse probability of treatment weighting was used to balance measured covariates.</p><p><strong>Results: </strong>Overall, 4,389 patients resumed oral anticoagulation, with 3016 (68.7%) on warfarin and 1373 (31.3%) on DOACs, within 90 days of hospital discharge for major GIB. The median (interquartile range) time from hospital discharge for major GIB to resumption of oral anticoagulant was 24 (10, 47) days. The weighted hazards ratio (HR) among individuals that resumed DOACs versus warfarin after major GIB was 0.76 (95% confidence interval, CI: 0.60, 0.96) for subsequent hospitalization for major bleeding, 0.91 (95% CI: 0.53, 1.55) for subsequent hospitalization for ischemic stroke/SE, and 0.83 (95% CI: 0.72, 0.97) for NACE.</p><p><strong>Conclusions: </strong>Among patients with AF who survived and resumed oral anticoagulation within the first 90 days after hospitalization for a major GIB event, restarting oral anticoagulation treatment with DOACs was associated with a lower risk of subsequent hospitalization for major bleeding and the composite outcome of ischemic stroke, SE, all-cause mortality, and recurrent or incident major bleeding.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144964747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}