Clinical therapeutics最新文献

{"title":"Efficacy and Safety of Direct Oral Anticoagulants for Patients With Atrial Fibrillation With Glomerular Hyperfiltration: A Systematic Review and Meta-Analysis","authors":"Xinyi Gao BS ,&nbsp;Ziheng Jia BS ,&nbsp;Gary Tse MD, PhD, FRCP ,&nbsp;Gregory Y.H. Lip MD, FESC, FACC, FRCP ,&nbsp;Tong Liu MD, PhD, FESC, FHRS","doi":"10.1016/j.clinthera.2025.06.015","DOIUrl":"10.1016/j.clinthera.2025.06.015","url":null,"abstract":"<div><h3>Purpose</h3><div>The purpose of this study was to identify possible therapeutic benefits of direct oral anticoagulants (DOACs) compared with warfarin in subjects with supranormal renal function.</div></div><div><h3>Methods</h3><div>PubMed and Embase were systematically searched until September 25, 2022. Articles that met the prespecified selection criteria were included. The fixed-effects model was chosen if there is no significant heterogeneity. Subgroup analyses were conducted to find the sources of heterogeneity. Variables that might expand heterogeneity were selected as follows: (1) type of DOAC, (2) dose of DOAC, (3) equation for glomerular filtration rate estimation, and (4) types of original research.</div></div><div><h3>Findings</h3><div>A total of 7 studies involving 87,514 patients were included. In patients with creatinine clearance (CrCl) &gt;80 mL/min, DOACs were associated with a significant reduction in the overall effectiveness outcomes compared with warfarin (hazard ratio [HR] = 0.75; 95% CI, 0.66–0.86; <em>P</em> &lt; 0.0001; <em>I</em>² = 66%), but not for stroke/systematic embolism (HR = 0.90; 95% CI, 0.72–1.14; <em>P</em> = 0.40; <em>I</em>² = 17%). Similarly, DOACs showed a decreased risk of safety outcomes compared with warfarin (HR = 0.68; 95% CI, 0.63–0.74; <em>P</em> &lt; 0.0001; <em>I</em>² = 45%). In patients with CrCl &gt;95 mL/min, DOACs were associated with a borderline lower risk of effectiveness outcomes (HR = 0.83; 95% CI, 0.68–1.01; <em>P</em> = 0.07; <em>I</em>² = 61%) and significantly lower risk of safety outcomes (HR = 0.66; 95% CI, 0.58–0.76; <em>P</em> &lt; 0.0001; <em>I</em>² = 0%), particularly major bleeding (HR = 0.63; 95% CI, 0.53–0.76; <em>P</em> &lt; 0.0001; <em>I</em>² = 0%) and intracranial hemorrhage (HR = 0.43; 95% CI, 0.30–0.62; <em>P</em> &lt; 0.0001; <em>I</em>² = 0%).</div></div><div><h3>Implications</h3><div>In patients with atrial fibrillation and CrCl &gt;80 mL/min, DOACs have greater clinical benefits than warfarin. For those with atrial fibrillation and CrCl &gt;95 mL/min, significantly better safety outcomes were observed for DOACs.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"47 9","pages":"Pages 798-806"},"PeriodicalIF":3.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144667373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reduced Use of Maintenance Therapies Among People With Cystic Fibrosis Following Initiation of Elexacaftor/Tezacaftor/Ivacaftor in Australia","authors":"Hans Kristian Råket MD PhD ,&nbsp;Tamara Milder MBBS MMed FRACP PhD ,&nbsp;Melisa Litchfield MSc ,&nbsp;Camilla Bjørn Jensen PhD ,&nbsp;Joanna Nan Wang MD ,&nbsp;Espen Jimenez-Solem MD PhD ,&nbsp;Janne Petersen PhD ,&nbsp;Sallie-Anne Pearson PhD ,&nbsp;Adam Jaffe MD FRCP FRCPCH FRACP ,&nbsp;Michael O. Falster PhD","doi":"10.1016/j.clinthera.2025.05.016","DOIUrl":"10.1016/j.clinthera.2025.05.016","url":null,"abstract":"<div><h3>Purpose</h3><div>Elexacaftor/tezacaftor/ivacaftor (ETI) is an efficacious targeted therapy for cystic fibrosis, but its impact on the use of maintenance therapies has not been assessed in Australia.</div></div><div><h3>Methods</h3><div>We performed a retrospective cohort study including individuals with at least 1 ETI dispensing. Quarterly prevalence of airway therapies, antibiotics, and gastrointestinal and endocrine medications was evaluated 24 months before and after ETI initiation. Odds ratios for dispensing were estimated using mixed-effects logistic regression.</div></div><div><h3>Findings</h3><div>Airway therapies and oral/inhaled antibiotic use declined after ETI, whereas gastrointestinal and endocrine therapies remained stable.</div></div><div><h3>Implications</h3><div>Elexacaftor/tezacaftor/ivacaftor is associated with a reduced treatment burden in cystic fibrosis, supporting broader access.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"47 9","pages":"Pages 813-815"},"PeriodicalIF":3.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144368642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and Safety of Simnotrelvir-Ritonavir Compared With Nirmatrelvir-Ritonavir in the Treatment of COVID-19: Real-World Evidence From a Retrospective Cohort Study During the Prevalence of the Omicron EG.5 Variant","authors":"Yi Zhang MPharm ,&nbsp;Yuezhen Zhu MSc ,&nbsp;Hui Yang PhD ,&nbsp;Chunguo Jiang MD ,&nbsp;Wanying Chen BS ,&nbsp;Hui Zhang BS ,&nbsp;Xintong Zhang BS ,&nbsp;Han Wu BS ,&nbsp;Jia Li BS ,&nbsp;Zhuoling An PhD","doi":"10.1016/j.clinthera.2025.06.008","DOIUrl":"10.1016/j.clinthera.2025.06.008","url":null,"abstract":"<div><h3>Purpose</h3><div>The rapid spread of the coronavirus-2019 (COVID-19) Omicron EG.5 variant poses challenges to existing treatment strategies, and comparative real-world evidence between simnotrelvir-ritonavir and nirmatrelvir-ritonavir remains limited.</div></div><div><h3>Methods</h3><div>We conducted a single-center retrospective study from July 01 to December 31, 2023, involving outpatient-diagnosed COVID-19 patients. We performed a descriptive analysis of epidemiologic characteristics, followed by regression analysis to identify key factors. Efficacy and safety differences between simnotrelvir-ritonavir and nirmatrelvir-ritonavir were then compared.</div></div><div><h3>Findings</h3><div><span>A total of 545 patients were included, with 93.21% presenting with general symptoms, 88.81% with respiratory symptoms, 10.28% with gastrointestinal symptoms, and 9.36% with cardiovascular symptoms. Factors associated with delayed recovery included a BMI over 25 kg/m</span>² (<em>P</em> = 0.004), and symptoms lasting more than 3 days at presentation (<em>P</em><span> = 0.004). The efficacy of simnotrelvir-ritonavir and nirmatrelvir-ritonavir was comparable, with mean days to symptom recovery of 5.11 and 4.22 days, respectively. However, simnotrelvir-ritonavir had a higher incidence of adverse events<span> (20.59%) compared to nirmatrelvir-ritonavir (6.69%), primarily gastrointestinal disorders.</span></span></div></div><div><h3>Implications</h3><div>During the Omicron EG.5 epidemic, general and respiratory symptoms predominated, with delayed recovery associated with being overweight, late treatment initiation, and multiple comorbidities. Simnotrelvir-ritonavir and nirmatrelvir-ritonavir demonstrated comparable efficacy, while simnotrelvir-ritonavir had a poorer safety profile.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"47 9","pages":"Pages 696-705"},"PeriodicalIF":3.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144564638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Use of Breasted Manikins During Community Cardiopulmonary Resuscitation Trainings in India and United States","authors":"Pavitra Kotini-Shah MD ,&nbsp;Priyamadhaba Behera MD ,&nbsp;Elizabeth Froelich PM ,&nbsp;Sritam Swarup Jena MD ,&nbsp;Alok Kumar Sahoo MD ,&nbsp;Ahana Gupta BA, BS ,&nbsp;Courtney Schwerin BS ,&nbsp;Shaveta Khosla PhD","doi":"10.1016/j.clinthera.2025.06.010","DOIUrl":"10.1016/j.clinthera.2025.06.010","url":null,"abstract":"","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"47 9","pages":"Pages 816-820"},"PeriodicalIF":3.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144658624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Nationwide Cohort Study on Antidepressant Use and Stroke Risk in Young Adults Aged 18–44 Years","authors":"Lu-Hsuan Wu Ph.D. ,&nbsp;Ching-Lan Cheng Ph.D. ,&nbsp;Yea-Huei Kao Yang BS Pharm. ,&nbsp;Swu-Jane Lin Ph.D.","doi":"10.1016/j.clinthera.2025.06.014","DOIUrl":"10.1016/j.clinthera.2025.06.014","url":null,"abstract":"<div><h3>Purpose</h3><div>Although serious adverse reactions to antidepressants, including stroke, are rare, they have gained increased attention. Many patients start antidepressant treatment at a young age, yet stroke risk among them remains understudied. This study aimed to assess stroke risk associated with antidepressant use across age groups, antidepressant classes, and treatment indications.</div></div><div><h3>Methods</h3><div>We conducted a cohort study using a new user approach, including adults aged 18–44 years in 2018. Overall, 119,751 antidepressant users and 119,751 non-users were matched by age, sex, and date of treatment initiation. Antidepressants, classified as N06A in the WHO Anatomical Therapeutic Chemical Classification System, were selected. The primary endpoint was the first stroke event within 180 days of treatment initiation.</div></div><div><h3>Finding</h3><div>Antidepressant use was associated with an increased stroke risk (hazard ratio [HR], 4.33; 95% confidence interval [CI] 2.30–8.14), particularly ischemic stroke (HR, 7.02; 95% CI 3.18–15.49), than hemorrhagic stroke (HR, 1.63; 95% CI 0.60–4.39). Elevated stroke risk was observed among users of tricyclic antidepressants and serotonin antagonist and reuptake inhibitors but not among users of selective serotonin or serotonin-norepinephrine reuptake inhibitors. A significantly higher stroke risk was noted among antidepressant users without psychiatric disorders (HR, 5.47; 95% CI, 2.58–11.61) or neurological disorders (HR, 4.10; 95% CI, 2.12–7.95) than among non-users.</div></div><div><h3>Implications</h3><div>Antidepressant use was associated with increased stroke risk in adults aged 18–44 years. However, the findings were limited by potential biases in administrative data and a lack of adjustment for socioeconomic and geographic disparities.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"47 9","pages":"Pages 720-728"},"PeriodicalIF":3.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144717701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Drastic Toll of Anti-Trans Legislation: Compromised Access to Health Care and Lost Research Opportunities","authors":"Lydia A. Fein MD, MPH ,&nbsp;Srivarun Tummarakota ,&nbsp;Rebecca Barnett MD, MPH ,&nbsp;Sara Danker MD","doi":"10.1016/j.clinthera.2025.07.011","DOIUrl":"10.1016/j.clinthera.2025.07.011","url":null,"abstract":"","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"47 9","pages":"Pages 665-666"},"PeriodicalIF":3.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144774839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Now What? Utilizing Adverse Drug Reporting Databases to Inform Care, Update Guidelines, and Improve Outcomes","authors":"Jill L. Maron MD, MPH","doi":"10.1016/j.clinthera.2025.07.013","DOIUrl":"10.1016/j.clinthera.2025.07.013","url":null,"abstract":"","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"47 9","pages":"Pages 663-664"},"PeriodicalIF":3.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144871828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cost-Effectiveness of Antiarrhythmic Drugs for Treating Paroxysmal or Persistent Atrial Fibrillation in China: An Economic Evaluation","authors":"Fuming Li MD ,&nbsp;Dunming Xiao MD ,&nbsp;Yu Xia PhD ,&nbsp;Junling Weng MD ,&nbsp;Shimeng Liu PhD ,&nbsp;Yingyao Chen PhD","doi":"10.1016/j.clinthera.2025.06.011","DOIUrl":"10.1016/j.clinthera.2025.06.011","url":null,"abstract":"<div><h3>Purpose</h3><div>Antiarrhythmic drug (AAD) therapies are foundational in the long-term management of atrial fibrillation (AF), yet there remains uncertainty in clinical and reimbursement decisions in China. This study aimed to estimate the cost-effectiveness of dronedarone compare to amiodarone and sotalol for the treatment of paroxysmal or persistent AF in China from the health system perspective.</div></div><div><h3>Methods</h3><div>A Markov decision model was developed to compare the lifetime clinical efficacy and costs of three AAD therapies associated with AF recurrence, congestive heart failure, strokes, and deaths due to AF or AF related complications. Model inputs were derived from the ATHENA trial results, real-world database, published literature, and supplemented from expert opinion. Cost-effectiveness was measured by the incremental cost-effectiveness ratio (ICER), defined as the incremental cost per quality-adjusted life year (QALY) gained among groups. One-way sensitivity, probabilistic sensitivity, and scenario analyses were performed to explore the uncertainty of the model.</div></div><div><h3>Findings</h3><div>This study used a simulated cohort with baseline characteristics of patients from the CCC-AF project. In the base case, compared to amiodarone and sotalol, dronedarone was expected to gain additional 1.28 QALYs (5.15 vs 3.87) and 1.78 QALYs (5.15 vs 3.37), with higher costs of $6632 ($11,025 vs $4393) and $6278 ($11,025 vs $4748) over a lifetime horizon, leading to ICERs of $5166 and $3524 per QALY, respectively. One-way sensitivity analysis revealed that the results were most sensitive to the relative risk of cardiovascular mortality, the discount rate of QALYs, and the utility for sinus rhythm. The probabilistic sensitivity analyses indicated that the probability of cost-effectiveness for dronedarone ranged from 97.0% to 99.4% at the threshold of one to three times China’s per capita gross domestic product in 2023, whereas the probability for amiodarone ranged from 3.0% to &lt;1%, and for sotalol was always &lt;1%. Scenario analyses confirmed that the base-case results were sufficiently reliable.</div></div><div><h3>Implications</h3><div>Our analysis suggests that dronedarone is a cost-effective AAD compared to amiodarone and sotalol for patients with paroxysmal or persistent AF in China, offering improvements in life expectancy and QALY in the long-term rhythm control.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"47 9","pages":"Pages 746-753"},"PeriodicalIF":3.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144689139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ANDEMBRY (garadacimab-gxii)","authors":"Paul Beninger MD, MBA","doi":"10.1016/j.clinthera.2025.07.020","DOIUrl":"10.1016/j.clinthera.2025.07.020","url":null,"abstract":"","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"47 9","pages":"Pages 823-824"},"PeriodicalIF":3.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144945732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of Oral β-Blockers in Patients With Acute Myocardial Infarction with Preserved or Mildly Reduced Left Ventricular Systolic Function: A Systematic Review and Meta-Analysis","authors":"Yi Chen PhD ,&nbsp;Jin Qiu ,&nbsp;Tao Ai ,&nbsp;Yanqing Wu PhD","doi":"10.1016/j.clinthera.2025.06.007","DOIUrl":"10.1016/j.clinthera.2025.06.007","url":null,"abstract":"<div><h3>Purpose</h3><div>In patients with acute myocardial infarction (AMI) and preserved or mildly reduced left ventricular ejection fraction (LVEF), there is clinical uncertainty about the effectiveness of β-blockers in reducing mortality. We therefore investigated the effect of oral β-blockers on clinical benefit in patients with AMI with preserved or mildly reduced LVEF.</div></div><div><h3>Methods</h3><div>We conducted a comprehensive systematic search using PubMed, Embase, Cochrane Library, and ClinicalTrials.gov from January 1, 2000 to May 1, 2025, and finally included 16 observational studies and 2 randomized controlled trials (RCTs) to assess the β-blockers on patients with AMI with preserved or mildly reduced LVEF. The primary outcome was all-cause death, and the secondary outcomes were cardiac death, major adverse cardiovascular events, recurrent MI, hospitalization for heart failure, and stroke.</div></div><div><h3>Findings</h3><div>According to the search strategy, we finally included 18 studies, of which 16 were observational studies and 2 were RCTs. In the 5 studies without propensity score matching data, all-cause death was significantly lower in the β-blocker group than in the no β-blocker group (odds ratio [OR]: 0.65; 95% CI, 0.53–0.80). In the propensity score-matched 10 observational researches and 2 RCTs, there were no significant differences in all-cause death between the 2 groups. β-Blockers seemed to significantly reduce all-cause death in both non–ST-segment elevation myocardial infarction and ST-segment elevation myocardial infarction (OR = 0.44; 95% CI, 0.24–0.82; OR = 0.62; 95% CI, 0.40–0.98). β-Blockers seemed to be more effective in lowering all-cause death and cardiac death in patients with AMI and an LVEF of 40% to 50% (OR = 0.70; 95% CI, 0.50–0.97), and in the group with a follow-up time of ≥ 3 years, the use of β-blockers was significantly more effective in reducing cardiac death compared with the group with a follow-up time of &lt;3 years (OR = 0.45; 95% CI, 0.23–0.88).</div></div><div><h3>Implications</h3><div>β-Blockers did not significantly reduce all-cause death and cardiac death in patients with AMI with preserved or mildly reduced LVEF. However, it seemed that patients with an LVEF of 40% to 50% might experience significant benefits in terms of long-term efficacy.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"47 9","pages":"Pages 788-797"},"PeriodicalIF":3.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144552537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}