Pharmacoepidemiology and Drug Safety最新文献

{"title":"DU-Vigilance; Capturing Unsuspected Problems in Drug Utilization.","authors":"Jesper Hallas, Hanin Harbi, Thomas Delvin, Lotte Rasmussen","doi":"10.1002/pds.70423","DOIUrl":"10.1002/pds.70423","url":null,"abstract":"","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"35 8","pages":"e70423"},"PeriodicalIF":2.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13419929/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148621044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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 Interaction Signals for Major Bleeding in Nursing Home Residents: High-Throughput Screening of Clopidogrel and Oral Anticoagulants.","authors":"Adam M D'Amico, Melissa R Riester, Charles E Leonard, Daniel A Harris, Lori A Daiello, Yu-Chia Sam Hsu, Douglas P Kiel, Meghan A Cupp, Kaleen N Hayes, Andrew R Zullo","doi":"10.1002/pds.70441","DOIUrl":"10.1002/pds.70441","url":null,"abstract":"<p><strong>Purpose: </strong>Nursing home (NH) residents are at high risk for major bleeding and are frequently exposed to complex medication regimens that may increase the likelihood of clinically important drug-drug interactions (DDIs). However, DDI evidence from community-dwelling populations may not generalize to NH residents, and real-world signals involving clopidogrel and oral anticoagulants remain incompletely characterized in this setting. We aimed to identify and interpret candidate DDI signals for major bleeding involving clopidogrel and oral anticoagulants among NH residents.</p><p><strong>Methods: </strong>Using linked Minimum Data Set assessments and Medicare fee-for-service claims (2013-2020), we conducted high-throughput, self-controlled case series (SCCS) screening analyses for four object drugs (clopidogrel, apixaban, rivaroxaban, and warfarin) paired with candidate precipitant medications. We estimated rate ratios (RRs) and 95% confidence intervals (CIs) comparing periods of concomitant use versus object drug use alone, applying semi-Bayes shrinkage to reduce false-positive signals. To aid interpretation, we incorporated two negative controls: a negative-control object drug (pravastatin) and a negative-control outcome (fall-related injury). A panel of experts evaluated signals for biological plausibility and potential bias.</p><p><strong>Results: </strong>After semi-Bayes adjustment, 5/40 clopidogrel, 1/29 apixaban, 2/15 rivaroxaban, and 6/22 warfarin signals remained significant, and none did for pravastatin. Signals were also observed for fall-related injury. Experts identified only clopidogrel/sertraline and warfarin with cephalexin, sulfamethoxazole-trimethoprim, and furosemide as biologically plausible signals.</p><p><strong>Conclusion: </strong>SCCS screening for DDIs in NH residents identified bleeding signals for clopidogrel and oral anticoagulants, but few were mechanistically coherent and fall-related injury signals suggested residual bias.</p>","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"35 8","pages":"e70441"},"PeriodicalIF":2.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13396814/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148579554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Active Safety Surveillance Using Real-World Evidence (ASSURE) Implementation: Transparent and Reproducible Real-World Evidence Standardized Framework to Support Safety Signal Evaluation.","authors":"Kevin Haynes, Jenna Reps, Jill Hardin, Eva-Maria Didden, James Gilbert, Joel Swerdel, Justin Bohn, Mitchell M Conover, Amir Sarayani, Anthony G Sena, Emily Yost, Valerie van Baalen, Kourtney Davis, Patrick Ryan, Martijn Schuemie","doi":"10.1002/pds.70435","DOIUrl":"10.1002/pds.70435","url":null,"abstract":"<p><strong>Purpose: </strong>To summarize experience with Johnson & Johnson's novel Active Safety Surveillance Using Real-world Evidence (ASSURE) program for producing efficient, transparent, applicable, and impactful RWE to support routine pharmacovigilance processes.</p><p><strong>Methods: </strong>ASSURE follows a stepwise framework that encompasses database diagnostics to assess fit-for-purpose real-world data (RWD) sources in the US, France, Germany, Australia, and Japan, phenotype development, query specification, and analytic implementation, objective study validity diagnostics, and standardized reporting. Licensed RWD sources are transformed into the Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM), from which we generate evidence for safety signal evaluation questions using a suite of open-source analytic tools made publicly available through the OHDSI community. For each signal evaluation request involving a medication exposure and outcome(s), we conducted population characterization and population-level causal effects estimation. Target medication, comparator medication, and indication cohorts utilize predefined phenotypes, when available, for rapid analytics. We provide an evaluation of the initial implementation of this framework, including results from database diagnostics, phenotype development, and objective study validity diagnostics applied prior to unblinding evidence to prevent exposing biased estimates. We defined efficiency as the time from query to results and integration of results into safety decisions.</p><p><strong>Results: </strong>The initial 19 months of the ASSURE program supported 110 safety signal evaluations across 24 unique products that arose from 47 requests. 74 evaluations (67%) passed study diagnostics and yielded effect estimation results with 62 (54%) providing propensity-score adjusted comparative cohort method results and 40 (36%) providing self-controlled case series results. Many analyses failed one or more diagnostics, preventing the generation and unblinding of potentially biased results: database (7 evaluations), phenotype specification (3 evaluations), or the requisite objective study validity diagnostics (26 evaluations). These 26 evaluations (24%) all provided population characterizations of exposure, indication, and outcome, including incidence rates.</p><p><strong>Conclusions: </strong>The ASSURE framework and implementation process, in collaboration with safety management teams, enables rapid response to medical product safety signals under evaluation and produces actionable RWE that supports pharmacovigilance decision making within regulatory timeframes.</p>","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"35 8","pages":"e70435"},"PeriodicalIF":2.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13397054/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148579560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-World Data for Safety Studies: Challenges and Opportunities From the Italian Multiple Sclerosis and Related Disorders Register.","authors":"Marco Salivetto, Tommaso Guerra, Pasquale Paletta, Vito Lepore, Paola Mosconi, Pietro Iaffaldano, Michela Ponzio","doi":"10.1002/pds.70432","DOIUrl":"10.1002/pds.70432","url":null,"abstract":"<p><strong>Introduction: </strong>Information on the safety profile of disease-modifying therapies (DMTs) in multiple sclerosis (MS) is often lacking in routine clinical practice. Real-world data sources, such as patient registries, support pharmacovigilance to characterise safety signals, as recently recognised by regulatory agencies. In Italy, the \"Italian Multiple Sclerosis and Related Disorders Register\" (RISM) was officially launched in 2015 to collect demographic and clinical data from patients with MS.</p><p><strong>Purpose: </strong>To describe the main characteristics of RISM as a research platform supporting the safety evaluation of MS therapies.</p><p><strong>Methods: </strong>RISM enables the systematic characterisation of clinical events occurring in treated patients and, over the years, has implemented procedures to ensure high-quality data collection. A study cohort including subjects who initiated a DMT between 2016 and 2025 is analysed using descriptive statistics. Clinical events recorded during the study period are reported as absolute numbers and frequencies.</p><p><strong>Results: </strong>Between 2016 and 2025, a total of 24 259 subjects received at least one DMT, and 4419 of them (18.2%) experienced one or multiple clinical events. For descriptive purposes, the occurrence of infections and malignancies, which accounted for 29.4% and 3.7% of all the clinical events collected in RISM respectively, are reported and categorised.</p><p><strong>Conclusions: </strong>This article outlines the strengths and limitations of RISM in conducting safety studies and highlights the methodological and legal challenges associated with such platforms. Routinely collected healthcare data within RISM provide a comprehensive, patient-centred perspective for the long-term evaluation of DMT safety and can address relevant questions on drug policies and public health.</p>","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"35 8","pages":"e70432"},"PeriodicalIF":2.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13420742/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148620974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Hierarchical Risk Assessment Framework for Population-Specific Statin Safety Labelling.","authors":"Leo Tsui","doi":"10.1002/pds.70440","DOIUrl":"10.1002/pds.70440","url":null,"abstract":"","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"35 8","pages":"e70440"},"PeriodicalIF":2.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13396966/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148579550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hospitalization for Malignant Arrhythmias Following Initiation of Donepezil: A Retrospective Cohort Study.","authors":"Yichang Huang, John-Michael Gamble, David N Juurlink, Mhd Wasem Alsabbagh","doi":"10.1002/pds.70426","DOIUrl":"10.1002/pds.70426","url":null,"abstract":"<p><strong>Purpose: </strong>Limited evidence suggests donepezil might pose an increased risk of malignant arrhythmias. We examined whether donepezil initiation was associated with a higher risk of hospitalization for malignant arrhythmia compared to other acetylcholinesterase inhibitors.</p><p><strong>Methods: </strong>Population-based cohort study using linked administrative databases from seven Canadian provinces (BC, AB, SK, MB, ON, PEI, NL). We included individuals aged ≥ 66 who were new users of donepezil, galantamine, or rivastigmine from April 1st, 2011, to January 31st, 2019. We used multivariable Cox proportional hazards regression to estimate the risk of hospitalization for malignant arrhythmia among new donepezil users compared to new users of galantamine or rivastigmine.</p><p><strong>Results: </strong>We identified 162 616 subjects (mean age 82, 40% male). Most (127 103; 78%) were treated with donepezil, while 25 597 (15.7%) received galantamine, (n = 6541; 4.0%) received oral rivastigmine, and (n = 3375; 2.1%) received transdermal rivastigmine. The median age was 82 years, and 59.8% were women. Baseline characteristics were generally well balanced. During a median follow-up of 386 days (maximum 2616 days), we identified 90 hospitalizations for malignant arrhythmias, including 58 in the donepezil group (23 per 100 000 person-years) and 32 for other AChEIs (44 per 100 000 person-years). Cumulative incidence curves showed a lower risk among donepezil initiators (Log-Rank p = 0.0026; Wilcoxon p = 0.0008). Crude regression suggested a reduced hazard (HR 0.52; 95% CI 0.34-0.80), which persisted after adjustment (aHR 0.55; 95% CI 0.36-0.85). In drug-specific analyses, donepezil initiators had a lower hazard relative to galantamine (aHR 0.49; 95% CI 0.31-0.77) but not rivastigmine (aHR 0.90; 95% CI 0.36-2.27). Sensitivity analyses-including alternative diagnosis field definitions, restricted follow-up, modified exclusion criteria, and propensity score adjustment-yielded consistent findings. No clear dose-response pattern was observed for any AChEI.</p><p><strong>Conclusion: </strong>In this population-based cohort study, initiation of donepezil was not associated with an increased risk of malignant arrhythmias compared to initiation of galantamine or rivastigmine.</p>","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"35 7","pages":"e70426"},"PeriodicalIF":2.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13364727/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148437411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"French Consumption of Methylphenidate in Primary Care From 2016 to 2023, Impact of Prescribing Policy Changes-A Time-Series Analysis.","authors":"Claire Saudreau, Vincent Tarazona, David De Bandt","doi":"10.1002/pds.70424","DOIUrl":"10.1002/pds.70424","url":null,"abstract":"<p><strong>Purpose: </strong>In France, methylphenidate, mainly used in the treatment of ADHD, has been subject to prescription restrictions that were relaxed at the end of 2021. This study analyses trends in methylphenidate consumption in France and examines changes following the modification to prescribing rules in 2021.</p><p><strong>Methods: </strong>This ecological study was based on data from the Medic'AM database, which records reimbursed outpatient drug dispensation in France from January 2016 to December 2023. Methylphenidate sales were expressed as defined daily dose per thousand inhabitants per day (DDD/TID) and expenditure as euros per thousand inhabitants. Time-series analyses were conducted to assess changes in methylphenidate sales and associated expenditure following modifications to prescribing arrangements in September and November 2021.</p><p><strong>Results: </strong>Methylphenidate consumption rose from 0.607 DDD/TID per month in 2016 to 1.457 DDD/TID in 2023, an increase of 84%. Associated expenditure followed a similar upward trend. A more pronounced increase in methylphenidate sales was observed after the end of 2021.</p><p><strong>Conclusion: </strong>The study shows a clear increase in methylphenidate sales after 2021, coinciding with changes in prescribing regulations. Given the ecological design, this temporal association cannot be interpreted as causal. The observed trends likely reflect multiple factors, including regulatory changes, increased recognition of ADHD, and evolving clinical practices. These findings highlight how changes in prescribing policies may be associated with variation in healthcare utilization and expenditure.</p>","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"35 7","pages":"e70424"},"PeriodicalIF":2.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13324226/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148368991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association Between Socioeconomic Conditions and Biologic Prescriptions for Inflammatory Bowel Diseases in the Brazilian Public Healthcare System: An Ecological Study.","authors":"Caroline Tianeze de Castro, Luciane Cristina Feltrin de Oliveira, Carlos Antonio de Souza Teles Santos, Djanilson Barbosa Dos Santos","doi":"10.1002/pds.70430","DOIUrl":"10.1002/pds.70430","url":null,"abstract":"<p><strong>Purpose: </strong>Inflammatory bowel diseases (IBD) are chronic conditions affecting millions of people globally. Brazil's public healthcare system provides free access to IBD medications. However, socioeconomic conditions may affect prescribing patterns. This study examined associations between income inequality, human development, and biologic prescription rates for IBD in the Brazilian public health system (SUS).</p><p><strong>Methods: </strong>Data from the SUS Outpatient Information System (2008-2022) were analyzed. The biologic prescription rate (percentage of biologic prescriptions among all IBD prescriptions) was the outcome of interest. Random-effects negative binomial regression for panel data evaluated associations between the Gini Index, Municipal Human Development Index (MHDI), and biologic prescriptions while controlling for demographic, social, and healthcare variables.</p><p><strong>Results: </strong>Biologic prescription rates for IBD in Brazil increased from 3.03% to 16.69%. Municipalities with higher income inequality had 6% lower prescription rates than those with higher income equality (RR 0.94; 95% CI 0.92-0.96). Using low MHDI as the reference, municipalities with medium (RR 0.79; 95% CI 0.70-0.91), high (RR 0.68; 95% CI 0.60-0.78), and very high MHDI (RR 0.66; 95% CI 0.58-0.76) had progressively lower rates.</p><p><strong>Conclusions: </strong>Income inequality and human development are associated with biologic prescription rates for IBD within the SUS. The paradoxical MHDI pattern probably reflects differential engagement of private health insurance across development levels, whereby biologic-eligible patients in wealthier municipalities access therapy outside the SUS and are not captured by SIA. These findings underscore the need for policies addressing structural disparities in IBD care and for future research integrating public and private sector prescription data.</p>","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"35 7","pages":"e70430"},"PeriodicalIF":2.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13355941/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148391338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel Recruitment, Data Collection, and Safety Reporting Methods in the Era of COVID-19: Design of a Post-Emergency Use Authorization COVID-19 Vaccination Safety-Surveillance Study.","authors":"Cherise Wong, Katherine Kendrick, Laura Webb, Lauren Cohen, M Patricia McAdams, Heather Rubino, Patrick Caubel, Emily O'Brien","doi":"10.1002/pds.70431","DOIUrl":"10.1002/pds.70431","url":null,"abstract":"<p><strong>Purpose: </strong>Within one week of the Food and Drug Administration granting the COVID-19 vaccine Emergency Use Authorization, the HERO-Together study launched. We describe how the study utilized novel methods for streamlined enrollment and longitudinal data collection to efficiently monitor early and long-term safety of the COVID-19 vaccine.</p><p><strong>Methods: </strong>HERO-Together is a fully remote, prospective observational cohort study, conducted through an online portal. Participants were recruited from an existing online community of healthcare workers that expanded to family and community members as vaccine eligibility expanded, as well as through marketing and point-of-vaccination efforts. Individuals received notifications to submit data at scheduled intervals for two years, and automated reminders prompted participants with missed check-ins, with centralized call center outreach for non-responders.</p><p><strong>Results: </strong>Multiple recruitment approaches were adopted, including direct outreach, national and local media campaigns, downloadable enrollment toolkits (e.g., social media), social media influencer partnerships, and pharmacy referrals. A study population of n = 19, 858 was enrolled within nine months of emergency use authorization, most self-reporting as white, female, working in healthcare, and all for whom variable survey completion was observed.</p><p><strong>Conclusion: </strong>Collectively, diverse recruitment strategies, data collection through the online portal, and electronic consent enabled rapid, decentralized enrollment of study participants in order to remotely monitor COVID-19 vaccine safety during the early days of the pandemic.</p><p><strong>Trial registration: </strong>EUPAS38671.</p>","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"35 7","pages":"e70431"},"PeriodicalIF":2.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13357033/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148430857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-Term Cardiovascular Risks of Anticholinergic Versus Non-Anticholinergic Antidepressants: A Target Trial Emulation With Negative Control Correction.","authors":"Yang Xu, Hong Xu, Jinxin Guo, Qoua Liang Her, Ruyu Li, Yongjie Lai, Yue Zhang, Edwin C K Tan, Siyan Zhan","doi":"10.1002/pds.70434","DOIUrl":"10.1002/pds.70434","url":null,"abstract":"<p><strong>Purpose: </strong>Antidepressants remain widely prescribed worldwide, and the potential cardiovascular risks associated with their anticholinergic properties are poorly understood.</p><p><strong>Methods: </strong>We employed an active-comparator new-user design to emulate a target trial spanning 2006-2021 in UK Biobank. Participants aged ≥ 40 years with linked primary care records who newly initiated an anticholinergic vs. a non-anticholinergic antidepressant were included. The primary outcome was hospitalization or death from cardiovascular events. To adjust for measured and unmeasured confounding, we applied propensity score matching (PSM) with proximal causal inference (PCI) and negative control outcome calibration (NCOC) to estimate the intention-to-treat hazard difference (HD). Subgroup analyses were conducted by age, sex, socioeconomic status, lifestyle factors, apolipoprotein E genotype, and major comorbidities. Sensitivity analyses included data-driven negative control selection, alternative anticholinergic burden scale, comparisons across different anticholinergic burden levels, complete-case analysis, a 6-month induction period, and a 2-year washout period.</p><p><strong>Results: </strong>The study included 24 547 anticholinergic antidepressant users and 20 519 non-anticholinergic users. Measured covariates were balanced among 32 588 PS-matched participants with a median follow-up of 9.1 years. Negative control correction revealed anticholinergic antidepressant use was associated with increased risk of cardiovascular events (HD_{PSM + PCI}: 59.96 per 10 000 person-years [95% CI: 43.32, 76.60]; HD_{PSM + NCOC}: 31.35 [17.95, 45.26]). Elevated risks were observed for ischemic stroke, acute coronary syndrome, heart failure, arrhythmias, arterial disease, and venous thromboembolism. Results were consistent across subgroup and sensitivity analyses.</p><p><strong>Conclusions: </strong>Anticholinergic antidepressants may increase the risk of cardiovascular events compared with non-anticholinergic antidepressants. These findings underscore prioritizing therapeutic options with a lower anticholinergic burden in clinical practice.</p>","PeriodicalId":19782,"journal":{"name":"Pharmacoepidemiology and Drug Safety","volume":"35 7","pages":"e70434"},"PeriodicalIF":2.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13369797/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148448607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}