Annals of Pharmacotherapy最新文献

{"title":"Correlation Between Serum and CSF Concentrations of Midazolam and 1-Hydroxy-Midazolam in Critically Ill Neurosurgical Patients.","authors":"Julie E Farrar, Sylvia S Stefanos, Luis Cava, Tyree H Kiser, Scott W Mueller, Robert Neumann, Paul M Reynolds, Deb S Sherman, Robert MacLaren","doi":"10.1177/10600280241271130","DOIUrl":"https://doi.org/10.1177/10600280241271130","url":null,"abstract":"<p><strong>Background: </strong>Midazolam (MZ) is commonly used in critically ill neurosurgical patients. Neuro-penetration of MZ and its metabolite, 1-hydroxy-midazolam (1-OH-MZ), is not well characterized.</p><p><strong>Objective: </strong>This study evaluated correlations between serum and cerebrospinal fluid (CSF) concentrations of MZ and 1-OH-MZ and assessed implications on patient sedation.</p><p><strong>Methods: </strong>Adults in the neurosurgical intensive care unit (ICU) with external ventricular drains receiving MZ via continuous infusion were prospectively studied. Serum and CSF samples were obtained 12-24 h and 72-96 h after initiation, and concentrations were determined in duplicate by high-performance liquid chromatography with tandem mass spectrometry. Bivariate correlation analyses used Pearson coefficient.</p><p><strong>Results: </strong>A total of 31 serum and CSF samples were obtained from 18 subjects. At sampling, mean MZ infusion rate was 3.9 ± 4.4 mg/h, and previous 12-h cumulative dose was 51.4 ± 78.2 mg. Mean concentrations of MZ and 1-OH-MZ in serum and CSF were similar between timepoints. Similarly, ratios of 1-OH-MZ to MZ in serum and CSF remained stable over time. Serum MZ (126.2 ± 89.3 ng/mL) showed moderate correlation (r² = 0.68, P < 0.001) with serum 1-OH-MZ (17.7 ± 17.6 ng/mL) but not CSF MZ (3.9 ± 2.5 ng/mL; r² = 0.24, P = 0.005) or CSF 1-OH-MZ (2.5 ± 0.6 ng/mL; r² = 0.47, P = 0.30). CSF MZ did not correlate with CSF 1-OH-MZ (r² = 0.003, P < 0.001). Mean serum ratio of 1-OH-MZ to MZ (0.14 ± 0.2 ng/mL) did not correlate with CSF ratio (1.06 ± 0.83 ng/mL; r² = 0.06, P = 0.19). Concentrations and ratios were unrelated to MZ infusion rate or 12-h cumulative dose. Sedation was weakly correlated with CSF 1-OH-MZ, but not with serum MZ, serum 1-OH-MZ, or CSF MZ.</p><p><strong>Conclusion and relevance: </strong>Continuous infusions of MZ result in measurable concentrations of MZ and 1-OH-MZ in CSF; however, CSF concentrations of MZ and 1-OH-MZ poorly represent serum concentrations or dosages. Accumulation of MZ and 1-OH-MZ in serum or CSF over time was not evident. Concentrations of MZ and 1-OH-MZ do not predict sedation levels, reinforcing that pharmacodynamic assessments are warranted.</p>","PeriodicalId":7933,"journal":{"name":"Annals of Pharmacotherapy","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142008149","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":"Impact of Dexmedetomidine Dosing and Timing on Acute Kidney Injury and Renal Outcomes After Cardiac Surgery: A Meta-Analytic Approach.","authors":"Hongpei Li, Lei Wang, Chunxia Shi, Baolong Zhou, Lan Yao","doi":"10.1177/10600280241271098","DOIUrl":"https://doi.org/10.1177/10600280241271098","url":null,"abstract":"<p><strong>Background: </strong>Acute kidney injury (AKI) is a common and serious complication following cardiac surgery. Dexmedetomidine, a highly selective α2-adrenergic agonist, has shown potential renoprotective effects, but previous studies have yielded conflicting results.</p><p><strong>Objective: </strong>This meta-analysis aimed to evaluate the efficacy and safety of dexmedetomidine in preventing AKI and reducing postoperative serum creatinine levels in adult patients undergoing cardiac surgery.</p><p><strong>Methods: </strong>We comprehensively searched 5 databases for randomized controlled trials comparing dexmedetomidine with control groups in adult cardiac surgery patients. The main outcomes were the incidence of AKI and change in postoperative serum creatinine levels. Meta-analyses were conducted using RevMan 5.4 models, and subgroup analyses were performed based on dexmedetomidine dosing and timing of administration. Continuous outcomes were combined and analyzed using either mean difference (M.D.), while dichotomous outcomes were analyzed using risk ratio (RR) with 95% confidence intervals (CI).</p><p><strong>Results: </strong>Our study included a total of 14 trials involving 2744 patients. Dexmedetomidine administration significantly reduced the incidence of AKI compared to control groups (RR = 0.54, 95% CI: 0.41-0.70, <i>P</i> < 0.00001). Postoperative serum creatinine levels were also lower with dexmedetomidine (MD = -0.14 mg/dL, 95% CI: -0.28 to -0.001, <i>P</i> =0.04). Subgroup analyses revealed that higher initial doses (>0.5 μg/kg) and administration during intraoperative and postoperative periods were associated with more pronounced renoprotective effects. Dexmedetomidine did not significantly affect mortality but reduced the duration of the length of hospital stay and mechanical ventilation.</p><p><strong>Conclusions and relevance: </strong>This meta-analysis demonstrates that dexmedetomidine administration, particularly at higher doses and during both intraoperative and postoperative periods, reduces the risk of AKI in adults undergoing cardiac surgery. These findings support the use of dexmedetomidine as a preventive strategy to enhance renal outcomes in this population.</p>","PeriodicalId":7933,"journal":{"name":"Annals of Pharmacotherapy","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142008150","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":"Tenecteplase Versus Alteplase: A Comparison of Bleeding Outcomes in Massive Pulmonary Embolism (TACO-PE).","authors":"Jacquelyn Crawford, Austin Roe, Jessica Brumit, Vera Wilson, Jen Tharp","doi":"10.1177/10600280241271264","DOIUrl":"https://doi.org/10.1177/10600280241271264","url":null,"abstract":"<p><strong>Background: </strong>Thrombolysis is recommended in the setting of massive pulmonary embolism (PE) for reperfusion of vessels but carries a serious concern for increased bleed risk. In October 2022, our institution adopted tenecteplase as the formulary thrombolytic. Previous literature is unclear regarding the bleed risk of tenecteplase in massive PE, and no study has yet compared safety outcomes with the current standard of care, alteplase.</p><p><strong>Objective: </strong>The objective of this study was to compare the incidence of bleeding with tenecteplase versus alteplase in massive PE patients.</p><p><strong>Methods: </strong>This was a retrospective, observational cohort study that included adults who received tenecteplase or alteplase for massive PE. The primary outcome was major bleeding as defined by the International Society on Thrombosis and Hemostasis (ISTH). Secondary outcomes included incidence of symptomatic intracranial hemorrhage (ICH), in-hospital mortality, administration of reversal agents, and length of stay.</p><p><strong>Results: </strong>A total of 44 patients met inclusion criteria with 20 patients in the alteplase cohort and 24 in the tenecteplase cohort. Seventeen percent of tenecteplase patients compared with 5% of alteplase patients experienced bleeding. The mortality rate was 83% vs 75%, respectively. In addition, 1 patient in the tenecteplase cohort experienced a symptomatic ICH and 2 patients required initiation of massive transfusion protocol.</p><p><strong>Conclusion and relevance: </strong>Although this study was limited in sample size, these results suggest that there may be reason for concern of higher bleeding rates in patients treated with tenecteplase in the setting of massive PE.</p>","PeriodicalId":7933,"journal":{"name":"Annals of Pharmacotherapy","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142008153","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":"Safety of Phenobarbital Versus Benzodiazepines for Alcohol Withdrawal in Critically Ill Patients With Primary Neurologic Injuries.","authors":"Robert Deveau, Adrian Wong, Mary Eche, Tuyen Yankama, Corey R Fehnel","doi":"10.1177/10600280241271156","DOIUrl":"https://doi.org/10.1177/10600280241271156","url":null,"abstract":"<p><strong>Background: </strong>Alcohol withdrawal syndrome (AWS) is a complication of alcohol use disorder that manifests as a range of symptoms. Symptom-triggered benzodiazepines (BZDs) are often used as first-line treatment of AWS. However, recent literature suggests phenobarbital (PHB) may be safer and more efficacious, but studies are limited by exclusion of patients with neurological injuries.</p><p><strong>Objective: </strong>We aimed to evaluate the safety of PHB compared to BZDs for the management of AWS among patients with primary neurologic injuries.</p><p><strong>Methods: </strong>Retrospective cohort study of patients with primary neurologic injuries admitted to an ICU who received PHB or symptom-triggered BZD for AWS between December 2013 and February 2020. The primary outcome was incidence of oversedation, defined as Richmond Agitation Sedation Scale (RASS) scores from -5 to -3 within 24 hours of initial PHB or BZD dose. Secondary outcomes included largest decrease in RASS, need for mechanical ventilation, and additional sedative use within 24 hours of initial PHB or BZD dose. A multivariable analysis was performed to evaluate the association of PHB administration with the primary outcome.</p><p><strong>Results: </strong>Among 600 patients treated for AWS, 84 patients were included in our analysis (PHB, n = 56; BZD, n = 28). In the unadjusted analysis, there were no differences between the PHB and BZD groups for the primary outcome of oversedation (21.4 vs. 7.1%, <i>P</i> = 0.13), or secondary outcomes of decrease in RASS (<i>P</i> = 0.34), or new ventilator requirement (<i>P</i> = 0.55). Patients who received PHB had higher rates of additional sedative use (<i>P</i> < 0.01). Multivariable regression revealed an increase in oversedation among intubated patients (<i>P</i> = 0.014), while PHB administration was not independently associated with oversedation (<i>P</i> = 0.516).</p><p><strong>Conclusion and relevance: </strong>Phenobarbital did not independently increase the risk of oversedation compared to BZD for AWS in patients with primary neurologic injuries. Future studies should determine optimal dosing of PHB in this population.</p>","PeriodicalId":7933,"journal":{"name":"Annals of Pharmacotherapy","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142008152","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":"Multiple Adverse Reactions Associated With the Use of Second-Generation Antipsychotics in People With Alzheimer's Disease: A Pharmacovigilance Analysis Based on the FDA Adverse Event Reporting System.","authors":"Jianxing Zhou, Zipeng Wei, Wei Huang, Maobai Liu, Xuemei Wu","doi":"10.1177/10600280241271093","DOIUrl":"https://doi.org/10.1177/10600280241271093","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease (AD) is a neurodegenerative condition leading to memory loss, cognitive impairment, and neuropsychiatric symptoms. Second-generation antipsychotics (SGAs) are commonly used to manage these neuropsychiatric symptoms, but their safety profile in patients with AD requires further investigation.</p><p><strong>Objective: </strong>The objective was to evaluate the safety of SGAs in patients with AD by analyzing adverse drug reactions (ADRs) using the US Food and Drug Administration Adverse Event Reporting System (FAERS) database.</p><p><strong>Methods: </strong>This study conducted a comprehensive analysis of FAERS data from 2014 to 2023, focusing on ADRs in patients with AD treated with SGAs such as risperidone, quetiapine, olanzapine, clozapine, and aripiprazole. Descriptive, disproportionality, time, and dose analysis were performed using the Bayesian confidence propagation neural network, Weibull, and physiologically based pharmacokinetic model.</p><p><strong>Results: </strong>Out of 1289 patients with AD treated with SGAs, the most common ADRs involved the nervous system, gastrointestinal system, and cardiac disorders. Disproportionality analysis identified significant positive signals in cardiac, renal, and vascular systems. Quetiapine, risperidone, and olanzapine showed more positive signals compared with clozapine and aripiprazole. Time analysis indicated that cardiovascular ADRs occurred randomly, whereas renal ADRs increased with prolonged use. Dose analysis suggested that small doses of SGAs did not elevate the risk of multiple cardiac, renal, or vascular ADRs.</p><p><strong>Conclusion and relevance: </strong>The study underscores the importance of monitoring for ADRs, particularly in the cardiac and renal systems, when using SGAs in patients with AD. Future research incorporating more comprehensive clinical data is warranted to support safe and rational drug utilization.</p>","PeriodicalId":7933,"journal":{"name":"Annals of Pharmacotherapy","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142008151","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":"Effect of Immune Thrombocytopenic Purpura Medications on Depression Risk: An Analysis of NHANES Data.","authors":"Feiyue Zheng, Zhengwei Yu, Zhang Zhang, Jinli Miao, Wenmin Wang, Jiaying Wu, Yuefeng Rao","doi":"10.1177/10600280241267930","DOIUrl":"https://doi.org/10.1177/10600280241267930","url":null,"abstract":"<p><strong>Background: </strong>Immune thrombocytopenic purpura (ITP) in adults typically develops slowly and insidiously. The ITP medications might be linked to psychological disorders, but the connection is not well-understood.</p><p><strong>Objective: </strong>This study aimed to examine the association between ITP medication use and the risk of depression among participants in the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2018.</p><p><strong>Methods: </strong>Using data from 70 190 NHANES participants, we conducted a cross-sectional study, excluding individuals under 18 years, with hypertension, HIV, hepatitis C, and various comorbidities. A total of 17 299 individuals were included in the analysis of this study. We identified 2 populations within this study: those using ITP medications, including prednisone, dexamethasone, and rituximab and those not using ITP drugs. Depression status was assessed using the Patient Health Questionnaire-9 (PHQ-9), and the relationship between ITP medication use and depression was analyzed through multivariate logistic regression.</p><p><strong>Results: </strong>There was no significant association between ITP medication use and an increased risk of depression after adjusting for demographic and health-related variables. Notably, among the study participants, 1.8% of the non-depressed population were on ITP medication compared with 0.3% in the depressed population. The analysis revealed varying depression risks associated with different sociodemographic factors. For instance, the correlation between ITP medication and depression risk was influenced by a combination of age, race, income, and smoking status.</p><p><strong>Conclusion and relevance: </strong>The study suggests that ITP medication use does not independently increase the risk of depression. This finding is crucial for guiding clinical decisions and managing patient expectations regarding ITP treatment and its psychological impacts.</p>","PeriodicalId":7933,"journal":{"name":"Annals of Pharmacotherapy","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141896563","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":"Evaluation of Newly Integrated Bivalirudin Titration Protocol in Patients With Mechanical Circulatory Support.","authors":"Madeline Mitchell, Danine Sullinger, Duke Dyer, Gavin Hickey, David Kaczorowski, Joni Minor, Holt Murray, Raj Ramanan, Zachary Rhinehart, Mark Schmidhofer, Ryan M Rivosecchi","doi":"10.1177/10600280231206130","DOIUrl":"10.1177/10600280231206130","url":null,"abstract":"<p><strong>Background: </strong>Patients with cardiogenic shock or end-stage heart failure can be maintained on mechanical circulatory support (MCS) devices. Once a patient undergoes placement of a device, obtaining and maintaining therapeutic anticoagulation is vital. Guidelines recommend the use of institutional protocols to assist in dosing and titration of anticoagulants.</p><p><strong>Objective: </strong>The purpose of this study was to characterize the use of bivalirudin before and after the implementation of a standardized titration protocol in patients with MCS.</p><p><strong>Methods: </strong>A retrospective review of patients who received bivalirudin for MCS (VA ECMO [veno-arterial extracorporeal membrane oxygenation], Impella, or LVAD [left ventricular assist device]) before and after the implementation of the titration protocol into the electronic health record (EHR) was conducted. The primary outcome was to compare the proportion of therapeutic activated partial thromboplastin time (aPTT). Secondary outcomes included number of subtherapeutic and supratherapeutic aPTTs, incidence of bleeding and clotting events, bivalirudin titrations per day, and percentage of patients with therapeutic aPTT level.</p><p><strong>Results: </strong>A total of 100 patients were included (precohort = 67; postcohort = 33). The proportion of therapeutic aPTTs was significantly higher in the postcohort than that in the precohort (62% vs 48%; <i>P</i> < 0.001). The postcohort had 0% of patients failing to achieve therapeutic aPTT levels. The number of titrations per day was significantly lower in the postcohort, with 1.20 titrations per day versus 1.93 in the precohort (<i>P</i> < 0.001).</p><p><strong>Conclusions: </strong>Implementation of the bivalirudin titration nomograms within the EHR significantly increased the number of therapeutic aPTTs, reduced the number of patients who never achieved a therapeutic aPTT, and reduced the required number of titrations per day.</p>","PeriodicalId":7933,"journal":{"name":"Annals of Pharmacotherapy","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54227369","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":"Real-World Experience With CMV inSIGHT T Cell Immunity Testing in High-Risk Kidney and Pancreas Transplant Recipients.","authors":"Jillian L Descourouez, Jeannina A Smith, Christopher M Saddler, Didier A Mandelbrot, Jon S Odorico, Margaret R Jorgenson","doi":"10.1177/10600280231207899","DOIUrl":"10.1177/10600280231207899","url":null,"abstract":"<p><strong>Background: </strong>Cytomegalovirus (CMV)-specific cell-mediated immunity is important for control of CMV after transplant. Assays exist to measure this, but their place in therapy is unclear, particularly in CMV high-risk recipients, without pretransplant exposure.</p><p><strong>Objective: </strong>The objective of this study was to evaluate predictive potential of a positive assay to determine freedom from DNAemia and describe subsequent 3-month CMV outcomes.</p><p><strong>Methods: </strong>Adult CMV high-risk kidney and/or pancreas transplant recipients were included if a CMV inSIGHT T Cell Immunity Panel (TCIP, Eurofins Viracor) was ordered and resulted between 1 August, 2019 and 30 July, 2022.</p><p><strong>Results: </strong>Seventy-six patients were included in our study; 49 tested during prophylaxis and 27 during treatment. Most TCIP assays obtained in the prophylaxis cohort were negative (n = 46, 93.9%). Rate of post-TCIP CMV infection was 10.2%. In those tested during treatment, 33.3% were positive and rate of post-TCIP CMV recurrence was 22.2%. The positive predictive value of the assay to successfully predict immunity was 66.7% during both prophylaxis and treatment. There were 4 cases of TCIP predictive failure with progressive CMV replication. At time of replication, 2 patients had concomitant clinical confounders thought to influence immune control of viral replication. All patients had intensification of immunosuppression prior to recurrent replication, but after TCIP was collected.</p><p><strong>Conclusion and relevance: </strong>The data obtained from the TCIP are not static, immune control of CMV in latency can change and must be evaluated in clinical context. Timing of TCIP after transplant is significant, and patient-specific factors remain important to assess the likelihood of CMV in each unique patient-specific scenario. A CMV stewardship program can aid in application and interpretation of results.</p>","PeriodicalId":7933,"journal":{"name":"Annals of Pharmacotherapy","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66783496","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":"Combination of Rivaroxaban and Amiodarone Increases Bleeding in Patients With Atrial Fibrillation.","authors":"Zi Wang, Xiaoyu Li, Ye Zou, Xiaoye Li, Qianzhou Lv","doi":"10.1177/10600280231211306","DOIUrl":"10.1177/10600280231211306","url":null,"abstract":"<p><strong>Background: </strong>Rivaroxaban and amiodarone are commonly used for treating patients with atrial fibrillation. Drug-drug interactions between rivaroxaban and amiodarone may increase exposure to rivaroxaban. However, the clinical relevance of this drug-drug interaction is still not clear.</p><p><strong>Objective: </strong>The aim was to investigate the risk of bleeding in patients receiving a combination of rivaroxaban and amiodarone.</p><p><strong>Methods: </strong>This was a prospective observational study in which we included atrial fibrillation patients treated with rivaroxaban. The patients were divided into the rivaroxaban group and the combination of rivaroxaban and amiodarone group (the combination group). Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were performed to adjust between-group differences. The primary endpoint was defined as the time to the first occurrence of a composite of major, clinically relevant nonmajor, and minor bleeding.</p><p><strong>Results: </strong>In total, 481 atrial fibrillation patients were included in the analysis. After PSM, 154 patients in the rivaroxaban group were matched with 154 patients in the combination group. The bleeding events mainly consisted of clinically relevant nonmajor and minor bleeding. Only one patient experienced major bleeding. The primary outcome was recorded in 26.0% of patients in the combination group and 10.4% of patients in the rivaroxaban group (hazard ratio = 2.76, 95% CI = 1.55-4.93, <i>P</i> < 0.001). The bleeding risk was significantly higher in the combination group compared with that in the rivaroxaban group in the IPTW and stabilized IPTW analyses (hazard ratio = 2.17, 95% CI = 1.32-3.56, <i>P</i> = 0.002).</p><p><strong>Conclusion and relevance: </strong>The combination of rivaroxaban and amiodarone increased the risk of bleeding in patients with atrial fibrillation, especially clinically relevant nonmajor and minor bleeding. Physicians prescribing rivaroxaban and amiodarone together should be concerned about an increase in the risk of nonmajor bleeding.</p>","PeriodicalId":7933,"journal":{"name":"Annals of Pharmacotherapy","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92152288","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":"Valoctocogene Roxaparvovec and Etranacogene Dezaparavovec: Novel Gene Therapies for Hemophilia A and B.","authors":"John A Dougherty, Kristiann M Dougherty","doi":"10.1177/10600280231202247","DOIUrl":"10.1177/10600280231202247","url":null,"abstract":"<p><strong>Objective: </strong>To review efficacy and safety data of valoctocogene roxaparvovec (Roctavian) and etranacogene dezaparavovec (Hemgenix), novel gene therapies for the treatment of the life-threatening bleeding disorders hemophilia A and B, respectively.</p><p><strong>Data sources: </strong>A PubMed/Google Scholar search from inception through August 11, 2023 was conducted using the following keywords: <i>gene therapy</i>, <i>hemophilia A</i>, <i>hemophilia B</i>, <i>etranacogene dezaparavovec</i>, <i>valoctocogene roxaparvovec</i>, <i>and bleeding.</i></p><p><strong>Study selection and data extraction: </strong>Data, including phase 1 to 3 clinical trials (non-comparator), were obtained from primary literature and package inserts. These reports evaluated clinical pharmacology, efficacy, safety, adverse events, warnings, and precautions.</p><p><strong>Data synthesis: </strong>Valoctocogene phase 3 study in males (n = 134): 87% had factor VIII (FVIII) levels that at least met criteria for mild hemophilia. Etranacogene phase 3 study in males (n = 54): within 3 weeks of infusion, mean factor IX (FIX) levels had reached 26.8 IU/dL. Both therapies provided clinically and statistically significant decreases in bleeding events and prophylactic factor infusions. Most common adverse event was elevations in liver function tests that were treated with glucocorticoids.</p><p><strong>Relevance to patient care and clinical practice in comparison with existing drugs: </strong>The endogenous production of clotting factors mimics physiological production while decreasing morbidity and mortality related to bleeding events similar to the effects of existing replacement strategies. Gene therapy was also shown to increase patient quality of life.</p><p><strong>Conclusion: </strong>Valoctocogene and etranacogene provide another treatment for selected patients with hemophilia. Treatment for the patient with hemophilia (gene therapy vs replacement strategy) must be personalized as new clinical data are published being cognizant of drug affordability.</p>","PeriodicalId":7933,"journal":{"name":"Annals of Pharmacotherapy","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136395923","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}