British journal of clinical pharmacology最新文献

{"title":"Physiologically based pharmacokinetic modelling predicts altered maternal pharmacokinetics of amitriptyline during pregnancy.","authors":"Maike Scherf-Clavel, Anna Linda Leutritz, Andrea Gehrmann, Stefan Unterecker, Sebastian Walther, Sarah Kittel-Schneider","doi":"10.1002/bcp.70084","DOIUrl":"https://doi.org/10.1002/bcp.70084","url":null,"abstract":"<p><strong>Aims: </strong>Pharmacotherapy of maternal peripartum depression is an increasing challenge. Amitriptyline (AMI) is the most often used tricyclic antidepressant during pregnancy, but knowledge on pharmacokinetics in this special phase is lacking. Physiologically based pharmacokinetic (PBPK) modelling is a powerful tool to better understand pregnancy-induced pharmacokinetic changes of medication. We aimed to improve the knowledge about AMI pharmacokinetics during pregnancy using PBPK modelling. Consequently, we aimed to add new information for an effective and safe pharmacotherapy in pregnant women.</p><p><strong>Methods: </strong>A PBPK model, including AMI, but also its active metabolite nortriptyline (NOR), was developed to investigate pregnancy-induced pharmacokinetic changes after AMI administration. The predicted drug exposure was compared to observed concentrations in pregnant patients in clinical routine. The PBPK model was set up using PK-Sim Version 11.</p><p><strong>Results: </strong>Serum concentration profiles were described successfully. During pregnancy, active moiety serum concentration of AMI (AMI + NOR) did not change; however, AMI concentration increased, whereas NOR concentration decreased.</p><p><strong>Conclusions: </strong>With this model, we added valuable information on AMI pharmacokinetics during pregnancy (increased AMI concentration, decreased NOR concentration). For clinical practice the treating physician should be aware that despite active moiety serum concentration comparable to before pregnancy, tolerability may be affected due to increased AMI serum concentrations and as consequence increased anticholinergic effects. To keep the risk of therapy discontinuation during pregnancy low, we suggest performing therapeutic drug monitoring, especially to check the AMI serum concentration.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143959766","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":"A single-centre analysis of a biosimilar switching programme for adalimumab in inflammatory bowel disease.","authors":"Louise Rabbitt, Áine Keogh, Linda Duane, John Ferguson, Anna Hobbins, Brian E McGuire, Patrick Gillespie, Laurence J Egan","doi":"10.1002/bcp.70086","DOIUrl":"https://doi.org/10.1002/bcp.70086","url":null,"abstract":"<p><strong>Aims: </strong>Amgevita is a licensed biosimilar to adalimumab, having demonstrated high pharmacokinetic and clinical similarity to Humira. Switching to a lower-cost medicine may elicit a nocebo effect, whereby expectations of poorer efficacy impact outcomes despite pharmacological similarity. This prospective cohort study examined clinical and economic outcomes and associated psychosocial variables in a group of patients undergoing a nonmedical switch to biosimilar adalimumab.</p><p><strong>Methods: </strong>Patients with inflammatory bowel disease (IBD) were followed before and after switching from Humira to Amgevita. Objective disease activity was assessed pre- and post-switch using the Harvey-Bradshaw Index (Crohn's disease) or partial Mayo score (ulcerative colitis), faecal calprotectin and C-reactive protein. Subjective symptom burden was measured using the IBD Control Questionnaire (IBDCQ). Pre-switch, health anxiety was measured using the Health Anxiety Index (HAI).</p><p><strong>Results: </strong>In total, 64 patients aged 18-67 were enrolled. IBDCQ scores marginally improved post-switch (13.33 vs, 12.49, P = .043), with no significant changes in objective disease activity scores, faecal calprotectin or C-reactive protein. Sixteen patients reported 17 new adverse events within 4 weeks. Logistic regression revealed a significant relationship between HAI scores and adverse events (P = .0079); each unit increase in HAI score increased the odds of reporting an adverse event by 21%. Drug cost savings for the 64 patients over 8 weeks totalled €143 958.</p><p><strong>Conclusion: </strong>Switching to biosimilar adalimumab did not affect disease control or quality of life. 25% of patients developed new side effects, particularly those with high levels of health anxiety. Significant cost savings were achieved.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143966660","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":"Sodium-glucose cotransporter 2 inhibitor increases risk of urinary tract infection: Evidence from mendelian randomization and meta-analysis.","authors":"Jie Ren, Sining Yang, Yifei Wang, Rui Chen, Xing Zhang, Yang Feng, Fengping Zhang, Yifan Jia, Jingyao Zhang, Chang Liu","doi":"10.1002/bcp.70070","DOIUrl":"https://doi.org/10.1002/bcp.70070","url":null,"abstract":"<p><strong>Aims: </strong>Sodium-glucose cotransporter 2 inhibitor (SGLT2i) is a new hypoglycaemic drug with good effect. However, whether increased urine sugar also increases the risk of urinary tract infection (UTI) is still controversial.</p><p><strong>Methods: </strong>Mendelian randomization (MR) was used to explore the causal relationships between SGLT2i and UTI. To ensure the robustness of results of MR, we used 3 genome-wide association study (GWAS) datasets of UTI, which equates to 3 randomized controlled trials. Inverse variance weighted (IVW) was the most important method of MR. Sensitivity analysis was used to assess the robustness of MR. We also integrated the results of IVW by meta-analysis to further increase the confidence.</p><p><strong>Results: </strong>According to IVW, SGLT2i increased the risk of UTI in some results: UTI (odds ratio [OR]: 1.015, 95% confidence interval [CI]: 1.008-1.023, P = 7.121E-05); UTI (OR: 1.008, 95%CI: 1.000-1.016, P = .037); However, other result showed SGLT2i did not increase the risk of UTI: UTI (OR: 1.008, 95%CI: 0.996-1.020, P = .190). To further increase the robustness of the results, we integrated the IVW results through meta-analysis. The results of meta-analysis showed SGLT2i increased the risk of UTI (OR: 1.011, 95%CI: 1.006-1.016, P < .001).</p><p><strong>Conclusion: </strong>SGLT2i increases the risk of UTI. However, SGLT2i should not be abandoned because of the risk of UTI. The use of SGLT2i should be considered with caution only when the diabetes patient requires a high-dose use and has a history of complicated UTI. More clinical and experimental studies are needed to explore the broad effects and mechanisms of SGLT2i.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143974111","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":"Management of hypotension in dihydropyridine calcium channel blocker overdose: The role of high-dose insulin therapy.","authors":"Betty S H Chan, Katherine Z Isoardi, Darren M Roberts, Ong Sook Har","doi":"10.1002/bcp.70081","DOIUrl":"https://doi.org/10.1002/bcp.70081","url":null,"abstract":"<p><strong>Aims: </strong>Amlodipine poisoning is a leading cause of cardiovascular medication-related deaths, commonly managed with high-dose insulin (HDI) therapy. However, HDI is a vasodilator that is counterproductive in managing vasoplegia. We aim to study HDI therapy in patients with hypotension following dihydropyridine calcium channel antagonist (CCA) overdose.</p><p><strong>Methods: </strong>This retrospective study includes adult patients (≥15 years) with deliberate dihydropyridine CCA overdose and hypotension (mean arterial pressure <65 mmHg or systolic blood pressure <90 mmHg) managed by two Poisons Information Centres and three toxicology units in Australia (2020-2023). Patients who received HDI were compared with those who did not receive HDI therapy.</p><p><strong>Results: </strong>There were 50 patients (31 female [62%], median age 57 years). Forty-one (82%) coingested a renin-angiotensin system antagonist. Ten (20%) received HDI (median bolus dose of 1 U/kg and infusion 1.25 U/kg/h, interquartile range: 0.9-5.5) and 40 (80%) did not receive HDI therapy. Eight patients in the HDI had echocardiogram, 4 showed left ventricular dysfunction. There were no differences in the 2 groups regarding age, sex, median dose of dihydropyridine and renin-angiotensin system antagonists. Median minimal systolic blood pressure (P = .0007) and mean arterial pressure (P = .0006) were significantly lower prior to starting HDI. There were increased maximal concomitant number of vasopressors/inotropes used (median difference: 1.5; P = .0002) and at higher doses in the HDI group. Median dose of noradrenaline used was 1.15 μg/kg/min in the HDI group vs. 0.27 μg/kg/min in the non-HDI group (P = .003). One fatality occurred in the non-HDI group.</p><p><strong>Conclusion: </strong>Dihydropyridine CCA poisoning with associated hypotension was treated primarily with vasopressor therapy. The inodilator HDI was not commonly used, and it was primarily administered in low doses, utilized mainly in patients with left ventricular dysfunction.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143982069","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":"Turkish translation and cultural adaptation of the Ascertaining Barriers to Compliance taxonomy for medication adherence.","authors":"Cansu Goncuoglu, Emre Kara, Cengizhan Ceylan, Pınar Ay, Mesut Sancar, Betul Okuyan","doi":"10.1002/bcp.70077","DOIUrl":"https://doi.org/10.1002/bcp.70077","url":null,"abstract":"<p><strong>Aims: </strong>The aim of this study was to create a Turkish version of the Ascertaining Barriers to Compliance (ABC) taxonomy for medication adherence.</p><p><strong>Methods: </strong>A systematic literature search was conducted, followed by a national Delphi study using suggested methods of the International Society for Medication Adherence for translation of the ABC taxonomy for medication adherence. Three scientific databases (PubMed, TRDizin and ProQuest) were used in the systematic literature search to detect the terms and definitions and to identify a panel of Turkish-speaking experts in medication adherence. Three consecutive Delphi rounds were performed through online surveys. The consensus levels were categorized into moderate consensus (50-75%), consensus (>75-95%) and strong consensus (>95%).</p><p><strong>Results: </strong>Among 698 Turkish articles, adherence-related terms and definitions were derived from 20 studies, and a Delphi survey was created accordingly. The Delphi survey was sent to a total of 187 panellists. The response rates were 20.9, 71.8 and 92.9% in the rounds, subsequently. Most of the panellists were pharmacists (56.4%) and held a PhD degree (76.9%). In the 3 consecutive Delphi rounds, all ABC taxonomy terms reached at least moderate consensus, while most of the definitions reached at least moderate consensus except the definition of initiation.</p><p><strong>Conclusion: </strong>This study provided the Turkish ABC taxonomy for medication adherence and a minimum moderate level of consensus was reached for all the terms and most of the definitions. The Turkish ABC taxonomy should be used in education, research and clinical practice to promote and enable medication adherence in patients.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143966303","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":"A systematic review of manipulations to pharmaceutical dosage forms used in psychotropic tapering plans.","authors":"Denis O'Brien, Anne Marie Healy, Andrew Harkin, Cathal Cadogan","doi":"10.1002/bcp.70082","DOIUrl":"https://doi.org/10.1002/bcp.70082","url":null,"abstract":"<p><strong>Aims: </strong>To identify, evaluate and summarize all published literature that investigated manipulations to pharmaceutical dosage forms of psychotropic medications that could be used for the purposes of tapering.</p><p><strong>Methods: </strong>A systematic literature review was carried out of the available published literature on manipulations performed to psychotropic medications to obtain a decreased dose of the active pharmaceutical ingredient. All studies that involved the manipulation of pharmaceutical dosage forms of antidepressants or benzodiazepine receptor agonists and subsequent pharmaceutical analysis of active pharmaceutical ingredient content were eligible for inclusion. The electronic databases searched were: MEDLINE, Web of Science, EMBASE, PsycINFO and CINAHL.</p><p><strong>Results: </strong>Sixteen studies met inclusion criteria. The manipulation methods carried out in the identified studies involved tablet splitting (4 studies), formulation of liquid suspensions (8 studies) and diluting existing marketed liquid formulations (4 studies). Ten of the included studies reported a mean target dose recovery within the 95-105% range after the manipulation was performed. All studies in which a dilution was performed to an oral liquid formulation (n = 4) reported results within this percentage recovery range. None of the included studies investigated the accuracy of manipulations across the full dose range of a tapering schedule.</p><p><strong>Conclusion: </strong>This review identified a limited amount of published research on the accuracy of different methods of manipulating psychotropic medications. Diluting liquid formulations to achieve lower doses merits further investigation. Further research comparing different manipulation methods is also required to determine the best approach for tapering to lower doses.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143963887","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":"Implementing physician-led medication reviews for patients with diabetes and severe mental disorder: A randomized controlled trial.","authors":"Johan Frederik Mebus Meyer Christensen, Signe Wegmann Düring, Gesche Jürgens","doi":"10.1002/bcp.70062","DOIUrl":"https://doi.org/10.1002/bcp.70062","url":null,"abstract":"<p><strong>Aims: </strong>Patients with severe mental disorder and diabetes may be exposed to inappropriate polypharmacy increasing the risk of side effects and drug interactions. Although medication reviews may facilitate short-term deprescribing, they are not known to affect clinical outcomes. We investigated whether implementing physician-led medication reviews through interdisciplinary dialogue can change prescription patterns and improve pharmacological efficacy and tolerability in psychiatric outpatients with diabetes.</p><p><strong>Methods: </strong>Included in the study were 52 patients from an endocrinologist-psychiatrist outpatient clinic in Slagelse Region, Zealand, Denmark. Patients were allocated to an intervention group, where patients' pharmacological treatment was discussed at an interdisciplinary treatment conference based on a medication review conducted by a specialist in clinical pharmacology or a control group receiving standard care. All patients underwent psychometric testing, side effect screening, clinical interviews, and had drug regimens and biochemical test results extracted from the electronic health records at baseline and at 6 months follow up.</p><p><strong>Results: </strong>The trial was completed by 48 patients. Average time to follow up was 7 months (range 5-11 months). The intervention group had a median reduction of 1 drug (interquartile range [IQR] -4.00, 0.00) and 1 potentially inappropriate prescription (IQR -2.00, 0.00) compared to a median increase of 2 drugs (IQR 1.00, 3.00) and 2 potentially inappropriate prescriptions (IQR 0.00, 3.00) in the control group. The usage of both somatic and psychiatric drugs was reduced. We found no differences in clinical outcomes.</p><p><strong>Conclusion: </strong>Deprescribing can be achieved without worsening psychiatric symptoms in psychiatric outpatients by implementing physician-led medication reviews through interdisciplinary dialogue. This study was registered on ClinicalTrials.gov: NCT (05243160).</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143964020","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":"Towards greener prescribing? Swedish general practitioners' support for policies to reduce pharmaceutical pollution.","authors":"Johanna Villén, Johanna Laux, Björn Wettermark, Sofia Kälvemark Sporrong, Marmar Nekoro, Helle Håkonsen","doi":"10.1002/bcp.70066","DOIUrl":"https://doi.org/10.1002/bcp.70066","url":null,"abstract":"<p><strong>Aims: </strong>Prescribing pharmaceuticals is essential to improve health, but it also has substantial environmental impact. This study investigated the extent to which Swedish general practitioners (GPs) are willing to integrate environmental aspects into treatment decisions and their opinions on policies to reduce pharmaceutical pollution.</p><p><strong>Methods: </strong>A questionnaire assessing environmental considerations in prescribing was developed and distributed to 1233 Swedish GPs and physicians in training (response rate: 22%) between September 2023 and June 2024. It included 3 patient cases to assess trade-offs between therapeutic effect and environmental impact of pharmaceuticals used for pain management, blood pressure reduction, and contraception. Questions about attitudes to policies to reduce the environmental impact of pharmaceuticals were also included. Data were analysed using descriptive and inferential statistics.</p><p><strong>Results: </strong>Most respondents were willing to prescribe a less effective pharmaceutical if it was environmentally preferable, 77% for pain management and blood pressure reduction, and 50% for contraception. Environmental impact was ranked as the least important factor in prescribing decisions when compared to cost, regional treatment guidelines, dosage intervals, and user-friendliness. A total of 68% of respondents agreed that physicians should consider environmental aspects when prescribing, however only a few often searched for environmental information when prescribing. Policies directed towards other stakeholders, such as authorities and the pharmaceutical industry, received substantial support.</p><p><strong>Conclusion: </strong>Swedish GPs are willing to consider environmental factors when prescribing. However, other factors are more often considered and GPs attribute higher responsibility to other actors. Improving access to environmental information about pharmaceuticals could support greener prescribing.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143965978","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":"Implementation of mass pharmacogenetic testing: Dihydropyrimidine dehydrogenase testing prior to fluoropyrimidine treatment for patients.","authors":"Nisha Shaunak, Jessica Keen, Anna Kim, Munir Pirmohamed, William G Newman, Paul J Ross","doi":"10.1002/bcp.70057","DOIUrl":"https://doi.org/10.1002/bcp.70057","url":null,"abstract":"<p><strong>Aims: </strong>Pharmacogenomics enables personalization of drug therapy improving effectiveness and/or safety. Dihydropyrimidine dehydrogenase [DPYD] testing prior to fluoropyrimidine chemotherapy was commissioned by NHS England in response to an update from the Medicines and Healthcare products Regulatory Agency.</p><p><strong>Methods: </strong>A questionnaire developed and approved by the National DPYD Working Group investigated processes of testing, receiving and responding to results. The survey was distributed to Genomics Medicine Service Alliance (GMSA) Clinical Directors and Pharmacy Senior Responsible Officers for dissemination in their geography. Data were collected June-September 2021. All hospitals delivering fluoropyrimidines across the UK were invited to participate.</p><p><strong>Results: </strong>131/138 (94.9%) organizations reported testing all patients receiving fluoropyrimidines. In England 76.7% of hospitals sent samples to centrally commissioned genomics laboratories. In the devolved nations, 73.9% sent samples to regional genomics laboratories. Multidisciplinary staff including oncologists, independent non-medical prescribers, clinical nurse specialists, screening pharmacists and chemotherapy nurses requested the test, checked and actioned the result. Self-reported turnaround times varied from <2 days where a regional laboratory was colocated with a chemotherapy centre to >10 days.</p><p><strong>Conclusion: </strong>Through multiprofessional, national collaboration, this is the first report studying the large-scale rollout of a nationally commissioned pharmacogenetic test. Whilst DPYD testing has been successfully implemented, there is a need to standardize and improve end-to-end turnaround times. This has led to the development of a best practice pathway. Critically, GMSAs must build on this implementation to deliver its priorities, in supporting equitable access to future pharmacogenomic testing across a wider cohort of therapies.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143954587","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":"Propafenone- vs. amiodarone-associated adverse cardiac outcomes in patients with atrial fibrillation and heart failure.","authors":"Yi-Cheng Lin, Bi-Li Chen, Chien-Yi Hsu, Li-Ying Chen, Shing-Jong Lin, Gregory Y H Lip, Li-Nien Chien, Chun-Yao Huang","doi":"10.1002/bcp.70068","DOIUrl":"10.1002/bcp.70068","url":null,"abstract":"<p><strong>Aims: </strong>Clinical trials have shown an increased risk of death in patients with recent myocardial infarction who received antiarrhythmic drugs such as flecainide, encainide or moricizine, especially in the presence of associated structural heart disease such as cardiac dysfunction. This study aimed to evaluate the safety outcomes of propafenone use in atrial fibrillation patients with heart failure when compared to those of amiodarone use.</p><p><strong>Methods: </strong>This population-based cohort study used the National Health Insurance Research Database in Taiwan. Eligible patients were those who had atrial fibrillation or atrial flutter diagnosis, had heart failure diagnosis, and first received propafenone or amiodarone between 2002 and 2018. The primary endpoints were death due to arrhythmia and the composite proarrhythmic outcome, which consisted of sudden cardiac arrest, arrhythmic death, ventricular arrhythmia and implantation of defibrillator.</p><p><strong>Results: </strong>After propensity score matching, the study cohort consisted of 7235 propafenone and 14 470 amiodarone users. Compared to amiodarone, propafenone was associated with significantly lower risk of the composite proarrhythmic outcome (adjusted hazard ratio: 0.52; 95% confidence interval: 0.42-0.64; P < .001). Propafenone users also had lower risk of death owing to arrhythmia compared to amiodarone users (adjusted hazard ratio: 0.22; 95% confidence interval: 0.08-0.65; P = .006). Subgroup analysis and sensitivity analysis showed similar trends, favouring propafenone.</p><p><strong>Conclusion: </strong>Propafenone was not significantly associated with increased risk of proarrhythmia and mortality when compared to amiodarone in atrial fibrillation patients with heart failure in contemporary real-world settings. Prospective studies are needed to determine whether propafenone should definitely be avoided in these patients.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143983106","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}