American Journal of Cardiovascular Drugs最新文献

{"title":"COVID-19 Diagnosis, Oral Anticoagulation, and Stroke Risk in Patients with Atrial Fibrillation","authors":"Lanting Yang,&nbsp;Shangbin Tang,&nbsp;Jingchuan Guo,&nbsp;Nico Gabriel,&nbsp;Walid F. Gellad,&nbsp;Utibe R. Essien,&nbsp;Jared W. Magnani,&nbsp;Inmaculada Hernandez","doi":"10.1007/s40256-024-00671-3","DOIUrl":"10.1007/s40256-024-00671-3","url":null,"abstract":"<div><h3>Background</h3><p>Coronavirus disease 2019 (COVID-19) has been associated with an increased risk of stroke. It remains unclear whether the risk of stroke associated with a diagnosis of COVID-19 differed with oral anticoagulation (OAC) use. The aim of this study was to evaluate the association between COVID-19 infection, OAC use, and stroke in patients with atrial fibrillation (AF).</p><h3>Methods</h3><p>A retrospective cohort study was conducted in individuals with established AF using data from Optum’s deidentified Clinformatics^® Data Mart Database. Cox proportional hazard models with time-dependent variables were employed to assess the association between possession of OAC, COVID-19 diagnosis in both inpatient and outpatient setting, and time to ischemic stroke.</p><h3>Results</h3><p>A total of 561,758 individuals aged 77 ± 10 were included in the study, with a mean follow up time of 1.3 years. OAC use was associated with a reduced stroke risk [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.82–0.88]. COVID-19 infection was associated with an increased risk of stroke (HR 2.11, 95% CI 1.87–2.38); this increased risk was particularly pronounced for patients diagnosed with an inpatient diagnosis of COVID-19 (HR 3.95, 95% CI 3.33–4.68). There was no significant interaction between OAC use and COVID-19 diagnosis (<i>p</i> value = 0.96). As a result, the relative increase in stroke risk associated with COVID-19 did not differ between patients on OAC (HR 2.12; 95% CI 1.71–2.62) and those not on OAC (HR 2.11; 95% CI 1.83–2.43).</p><h3>Conclusion</h3><p>In a nationwide sample of patients with established AF, we found the relative increase in stroke risk associated with COVID-19 was independent of OAC use.</p></div>","PeriodicalId":7652,"journal":{"name":"American Journal of Cardiovascular Drugs","volume":"24 5","pages":"693 - 702"},"PeriodicalIF":2.8,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141970430","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":"Clinical Considerations for Healthcare Provider-Administered Lipid-Lowering Medications","authors":"Barry D. Bertolet,&nbsp;Katherine P. Cabral,&nbsp;Lance Sullenberger,&nbsp;Jan L. McAlister,&nbsp;Todd Sandroni,&nbsp;Dharmesh S. Patel","doi":"10.1007/s40256-024-00665-1","DOIUrl":"10.1007/s40256-024-00665-1","url":null,"abstract":"<div><p>Atherosclerotic cardiovascular disease (ASCVD), a leading cause of mortality and morbidity, is associated with a substantial healthcare and economic burden. Reduction of low-density lipoprotein cholesterol (LDL-C) to guideline-recommended goals is crucial in the prevention or management of ASCVD, particularly in those at high risk. Despite the availability of several effective lipid-lowering therapies (LLTs), up to 80% of patients with ASCVD do not reach evidence-based LDL-C goals. This nonattainment may be due to poor adherence to, and lack of timely utilization of, LLTs driven by a range of variables, including polypharmacy, side effects, clinical inertia, costs, and access issues. Inclisiran was approved by the US Food and Drug Administration in 2021 as a novel, twice-yearly, healthcare provider (HCP)-administered LLT. In-office administration allows HCPs more control of drug acquisition, administration, and reimbursement, and may allow for more timely care and increased patient monitoring. In the USA, in-office administered drugs are considered a Medical Benefit and can be acquired and reimbursed using the “buy-and-bill” process. Buy-and-bill is a standard system for medication administration already established in multiple therapeutic areas, including oncology, vaccines, and allergy/immunology. Initiating in-office administration will involve new considerations for clinicians in the cardiovascular specialty, such as the implementation of new infrastructure and processes; however, it could ultimately increase treatment adherence and improve cardiovascular outcomes for patients with ASCVD. This article discusses the potential implications of buy-and-bill for the cardiology specialty and provides a practical guide to implementing HCP-administered specialty drugs in US clinical practice.</p></div>","PeriodicalId":7652,"journal":{"name":"American Journal of Cardiovascular Drugs","volume":"24 6","pages":"729 - 741"},"PeriodicalIF":2.8,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s40256-024-00665-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141970429","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":"Apixaban Use in Patients with Kidney Impairment: A Review of Pharmacokinetic, Interventional, and Observational Study Data","authors":"Stephen R. Mandt,&nbsp;Noble Thadathil,&nbsp;Christian Klem,&nbsp;Cristina Russ,&nbsp;Patricia L. McNamee,&nbsp;Kevin Stigge,&nbsp;Dong Cheng","doi":"10.1007/s40256-024-00664-2","DOIUrl":"10.1007/s40256-024-00664-2","url":null,"abstract":"<div><p>Chronic kidney disease (CKD) remains a significant global health issue and is a leading cause of mortality worldwide. Patients with CKD have an increased risk of developing atrial fibrillation (AF) and venous thromboembolism (VTE). While direct oral anticoagulants (DOACs) have become a standard of care for anticoagulation (AC) in patients with AF and VTE, the appropriate use of these agents in comorbid kidney impairment warrants detailed discussion. This scientific narrative review summarizes the effectiveness and safety of apixaban use in patients with renal dysfunction by assessing the current published pharmacokinetic, interventional, observational, and guideline data. Apixaban is a highly selective, orally active, direct inhibitor of factor Xa, with well-established pharmacokinetics and consistent clinical outcomes across a broad range of patient populations, including those with kidney impairment. Overall, the scientific literature has shown that apixaban has a favorable clinical efficacy and safety profile compared with vitamin K antagonists for patients with AF or VTE and comorbid kidney impairment. These data support the approved label dosing strategy of apixaban in reducing the risk of stroke/systemic embolism in patients with nonvalvular AF and in treating VTE across all ranges of kidney function. Both clinician experience and knowledge of patient-specific factors may be required in the management of comorbid patients with advanced CKD or those requiring dialysis, as data on these patients are limited.</p></div>","PeriodicalId":7652,"journal":{"name":"American Journal of Cardiovascular Drugs","volume":"24 5","pages":"603 - 624"},"PeriodicalIF":2.8,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11344734/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141888201","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":"Characteristics and Impact of Randomized Trials on Drugs or Devices in Cardiovascular Medicine","authors":"Marco Spagnolo,&nbsp;Claudio Laudani,&nbsp;Antonio Greco,&nbsp;Daniele Giacoppo,&nbsp;Davide Capodanno","doi":"10.1007/s40256-024-00670-4","DOIUrl":"10.1007/s40256-024-00670-4","url":null,"abstract":"<div><h3>Introduction</h3><p>Clinical trials, essential for medical advancement, vary significantly in methodology and regulatory pathways depending on the type of therapeutic intervention (i.e., drugs or devices). This study aimed to determine whether the drug or device intervention types influence the impact of randomized trials in cardiovascular medicine.</p><h3>Methods</h3><p>We analyzed late-breaking randomized controlled trials presented at major cardiology conferences from 2015 to 2021. The primary endpoint was the total number of citations obtained. Secondary endpoints included the number of citations at 1 and 2 years, number of total and 1-year mentions, and several metrics of study conduct and publication. Statistical analysis included tests for comparisons of continuous or categorical variables, based on their distribution, as appropriate. To adjust the results for potential confounders, univariable and multivariable regression models were utilized. Additionally, sensitivity analyses were conducted to explore both the effect of neutral or positive study outcomes on the comparative impact of drug versus device trials and the impact of the coronavirus disease 2019 (COVID-19) pandemic on the primary endpoint.</p><h3>Results</h3><p>Of 382 eligible randomized trials, 227 (59.4%) were trials of drugs and 155 (40.6%) were trials of devices. Drug trials had a higher median number of total citations compared to device studies (93 [interquartile range {IQR} 48–137] vs. 82 [IQR 39–192]; <i>p</i> = 0.025). This difference was consistent at 1 and 2 years and was also observed in the number of total mentions and mentions at 1 year. All the metrics of study conduct and publication were similar, except for drug studies being more often stopped prematurely (8.8 vs. 1.9%; <i>p</i> = 0.006). After adjusting for multiple potential confounders, the difference in citations and mentions was no longer statistically significant. However, drug trials remained more likely to be stopped prematurely (adjusted odds ratio = 1.15; 95% confidence interval 1.03–1.28; <i>p</i> = 0.009). Positive study outcomes significantly influenced the number of citations and the likelihood of a trial being stopped prematurely.</p><h3>Conclusions</h3><p>Drug trials are often stopped early and receive more citations and mentions than device trials. However, these differences are mainly due to factors other than the treatment itself. Studies published simultaneously tend to get more attention, and drug trials with positive results are cited more often than those with neutral results.</p></div>","PeriodicalId":7652,"journal":{"name":"American Journal of Cardiovascular Drugs","volume":"24 5","pages":"651 - 661"},"PeriodicalIF":2.8,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11344709/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141858803","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 Cardiac Myosin Inhibitor Therapy for Hypertrophic Cardiomyopathy in Adults: A Contemporary Review","authors":"Jan K. Kalinski,&nbsp;Bo Xu,&nbsp;Ramone Boyd,&nbsp;Natalie Tasseff,&nbsp;Katy Rutkowski,&nbsp;Susan Ospina,&nbsp;Nicholas Smedira,&nbsp;Maran Thamilarasan,&nbsp;Zoran B. Popovic,&nbsp;Milind Y. Desai","doi":"10.1007/s40256-024-00667-z","DOIUrl":"10.1007/s40256-024-00667-z","url":null,"abstract":"<div><p>Hypertrophic cardiomyopathy (HCM) affects as many as 1 in 200 people in the adult population globally. Patients may present with exertional dyspnea, presyncope or syncope, atrial and ventricular arrhythmias, heart failure, and even sudden cardiac death. Current guideline-based therapy involves medical therapy for treatment of symptoms in milder forms of the disease and surgical or catheter-based septal reduction therapies in obstructive HCM. Until recently, there has existed a gap between these two approaches that is now being filled by a new class of drugs, cardiac myosin inhibitors, which directly target the underlying disease process in HCM. Current investigations examine the effects of two cardiac myosin inhibitors on reported symptoms, echocardiographic evidence of disease, and the associated need for septal reduction. This paper reviews the contemporary evidence for the use of cardiac myosin inhibitors in HCM in adults and highlights future directions for this exciting field of cardiovascular medicine.</p></div>","PeriodicalId":7652,"journal":{"name":"American Journal of Cardiovascular Drugs","volume":"24 5","pages":"591 - 602"},"PeriodicalIF":2.8,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11344715/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141726749","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":"Sodium-Glucose Cotransporter-2 Inhibitors: Elevating Standards in Cardiovascular Secondary Prevention","authors":"Antonio Greco","doi":"10.1007/s40256-024-00666-0","DOIUrl":"10.1007/s40256-024-00666-0","url":null,"abstract":"","PeriodicalId":7652,"journal":{"name":"American Journal of Cardiovascular Drugs","volume":"24 5","pages":"625 - 628"},"PeriodicalIF":2.8,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141625699","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 Use of Drugs that Should be Avoided or Used with Caution in Patients Hospitalized for Acute Decompensated Heart Failure","authors":"Marwan Sheikh-Taha","doi":"10.1007/s40256-024-00663-3","DOIUrl":"10.1007/s40256-024-00663-3","url":null,"abstract":"<div><h3>Background</h3><p>Heart failure (HF) is a pervasive global health concern, with acute decompensated heart failure (ADHF) contributing significantly to morbidity and mortality. Medications used in patients with HF may exacerbate HF or prolong the QT interval, posing additional risks.</p><h3>Objective</h3><p>The objective is to assess the prevalence and utilization patterns of medications known to cause or exacerbate HF and prolong the QT interval among patients with ADHF. Understanding these patterns is crucial for optimizing patient care and minimizing potential risks.</p><h3>Methods</h3><p>A retrospective chart review was conducted at Huntsville Hospital, Huntsville, USA, covering 602 patients with ADHF over a 40-month period. Inclusion criteria involved age ≥ 18 years, a history of HF, and ADHF admission. The 2016 American Heart Association Scientific Statement was used to identify drugs that may cause or exacerbate HF and those that could prolong the QT interval</p><h3>Results</h3><p>Among the 602 patients, 57.3% received medications causing or exacerbating HF, notably albuterol (34.9%) and diabetes medications (20.4%), primarily metformin, followed by urologic agents (14.3%), mostly tamsulosin, and nonsteroidal anti-inflammatory drugs (NSAIDs) (6.1%). Moreover, 82.9% were on medications prolonging the QT interval, with loop diuretics, amiodarone, ondansetron, and famotidine most prevalent. Furthermore, 42.1% of the patients received more than two concomitant medications that prolong the QT interval, which can further exacerbate the risk of torsades de pointes.</p><h3>Conclusion</h3><p>This study underscores the high prevalence of HF-causing or HF-exacerbating medications and QT-prolonging drugs in patients with ADHF. Healthcare professionals must be cognizant of these patterns, advocating for safer prescribing practices to optimize patient outcomes and reduce the burden of HF-related hospitalizations.</p></div>","PeriodicalId":7652,"journal":{"name":"American Journal of Cardiovascular Drugs","volume":"24 5","pages":"685 - 691"},"PeriodicalIF":2.8,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141554037","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":"Empagliflozin Effects in Patients with ST-Elevation Myocardial Infarction Undergoing Primary PCI: The EMI-STEMI Randomized Clinical Trial","authors":"Elnaz Khani,&nbsp;Naser Aslanabadi,&nbsp;Kazem Mehravani,&nbsp;Haleh Rezaei,&nbsp;Hoda Afsharirad,&nbsp;Taher Entezari-Maleki","doi":"10.1007/s40256-024-00662-4","DOIUrl":"10.1007/s40256-024-00662-4","url":null,"abstract":"<div><h3>Introduction</h3><p>Empagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, improves cardiovascular outcomes in heart failure patients, but data regarding the efficacy of empagliflozin in the setting of acute myocardial infarction (AMI) is still unclear. The current study aimed to evaluate whether treatment with empagliflozin before primary percutaneous coronary intervention (PCI) improves parameters associated with patients’ outcomes.</p><h3>Methods</h3><p>We randomly assigned 101 non-diabetic and non-heart failure patients with ST-elevation myocardial infarction (STEMI) who underwent primary PCI to receive either empagliflozin (10 mg before PCI and once daily for 40 days) or placebo, in addition to the standard treatment. The primary outcomes were changes in left ventricular ejection fraction (LVEF) 40 days after PCI, changes in cardiac troponin I (cTnI) and estimates of its area under the curve (AUC) and the peak level, and resolution of ST-segment in &gt; 50% of leads 90 min after PCI.</p><h3>Results</h3><p>No significant difference was observed in terms of the occurrence of ST-segment resolution &gt; 50% (46.0% versus 45.0%; <i>p</i> = 0.92) and the mean level of cTnI at each time point between the two groups. The estimated mean [standard deviation (SD)] AUC of cTnI was 955.0 (595.7) ng h/ml in the intervention and 999.7 (474.7) ng h/ml in the control groups (<i>p</i> = 0.85) without any significant difference in peak cTnI level. The mean (SD) LVEF 40 days after primary PCI was significantly higher in empagliflozin-treated patients than the placebo group [43.2% (5.8%) versus 39.2% (6.7%); <i>p</i> = 0.002].</p><h3>Conclusion</h3><p>In this study, no significant differences were observed across the groups in terms of cTnI levels and ST-segment resolution in patients with STEMI undergoing primary PCI. However, it shed light on the potential benefits of empagliflozin in improving LVEF following STEMI.</p><h3>Registration</h3><p>Iranian Registry of Clinical Trials Platform (https://irct.behdasht.gov.ir/) identifier number IRCT20111206008307N42.</p></div>","PeriodicalId":7652,"journal":{"name":"American Journal of Cardiovascular Drugs","volume":"24 5","pages":"673 - 684"},"PeriodicalIF":2.8,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141537434","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 SGLT2 Inhibitors on Atrial Fibrillation Recurrence after Catheter Ablation in Type 2 Diabetes Mellitus: A Meta-Analysis of Reconstructed Kaplan–Meier Curves with Trial Sequential Analysis","authors":"Youssef Soliman,&nbsp;Mohamed Abuelazm,&nbsp;Basma Ehab Amer,&nbsp;Mishaal Hukamdad,&nbsp;Mohamed Hatem Ellabban,&nbsp;Nada Ibrahim Hendi,&nbsp;Adel Mouffokes,&nbsp;Basel AbdelAzeem,&nbsp;Hatem Hassaballa","doi":"10.1007/s40256-024-00661-5","DOIUrl":"10.1007/s40256-024-00661-5","url":null,"abstract":"<div><h3>Purpose</h3><p>The role of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in managing cardiovascular outcomes in patients with type 2 diabetes mellitus (T2DM) is evolving. This meta-analysis seeks to explore the influence of SGLT2i on the recurrence of atrial fibrillation (AF) following catheter ablation (CA) in individuals with T2DM qualitatively and quantitatively.</p><h3>Methods</h3><p>A comprehensive literature search was conducted in electronic databases. Studies meeting predefined criteria were included. Individual patient data (IPD) were used from reconstructed time-to-event data to estimate hazard ratios (HRs) and 95% confidence intervals for AF recurrence. IPD meta-analysis was followed by a direct meta-analysis to assess the risk of AF recurrence.</p><h3>Results</h3><p>A total of five studies [one randomized controlled trial (RCT) and four cohort studies] were included in this study, and five studies were included in the qualitative analysis, while four studies comprising 1043 patients with T2DM were included in the quantitative analysis. The pooled Kaplan–Meier curve based on reconstructed data showed a significantly lower risk of AF recurrence in the SGLT2i group compared with all antidiabetic drugs (log-rank <i>P</i> = 0.00011) and dipeptidyl-peptidase IV inhibitors (DPP4i) (log-rank <i>P</i> = 0.01). Cox regression analysis showed consistent results. Direct meta-analysis showed that SGLT2i, compared with all antidiabetic medications (HR 0.57, 95% CI [0.44, 0.73], <i>I</i>²) and DPP4i (HR 0.41, 95% CI [0.24, 0.70], <i>I</i>²), was associated with a lower risk of AF recurrence.</p><h3>Conclusions</h3><p>SGLT2i are associated with a reduced risk of AF recurrence after CA in patients with T2DM. These results suggest that SGLT2i is promising in improving clinical outcomes for this population.</p></div>","PeriodicalId":7652,"journal":{"name":"American Journal of Cardiovascular Drugs","volume":"24 5","pages":"629 - 640"},"PeriodicalIF":2.8,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11344729/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141496857","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":"Effect of Activated Charcoal on Mavacamten Pharmacokinetics in Healthy Participants","authors":"Samira Merali,&nbsp;Manting Chiang,&nbsp;Caroline Sychterz,&nbsp;Longfei Chao,&nbsp;Tara Simmons,&nbsp;Yiru Xu,&nbsp;Alice Zhao,&nbsp;Massimo Attanasio,&nbsp;Bindu Murthy,&nbsp;Vidya Perera","doi":"10.1007/s40256-024-00659-z","DOIUrl":"10.1007/s40256-024-00659-z","url":null,"abstract":"<div><h3>Objective</h3><p>To assess the effect of activated charcoal on the single-dose pharmacokinetics of mavacamten when administered 2 h or 6 h after mavacamten dosing.</p><h3>Methods</h3><p>In this open-label, randomized, parallel-group study, healthy adults were randomized into three groups to receive mavacamten 15 mg alone or mavacamten 15 mg plus activated charcoal 50 g administered either 2 h or 6 h after mavacamten dosing. Pharmacokinetic parameters were derived from plasma concentration–time data using noncompartmental methods.</p><h3>Results</h3><p>Of the 45 participants randomized, 37 completed the study. When activated charcoal was administered 2 h after mavacamten dosing, mavacamten absorption and exposure were reduced compared with when mavacamten was administered alone: the area under the concentration–time curve from 0 to 72 h (AUC_0–72) and area under the concentration–time curve from time 0 extrapolated to infinity (AUC_INF) were reduced by 14% and 34%, respectively. The maximum plasma concentration (<i>C</i>_max) was also slightly lower when activated charcoal was administered 2 h after mavacamten dosing than with mavacamten alone. Pharmacokinetic profiles were similar for mavacamten alone and mavacamten plus activated charcoal administered 6 h after mavacamten dosing.</p><h3>Conclusions</h3><p>Activated charcoal was successful in reducing mavacamten absorption and exposure when administered as soon as possible after identification of a need for adsorption (2 h after mavacamten dosing). No change in exposure was observed when activated charcoal was administered 6 h after mavacamten dosing.</p><h3>Clinical Trial Registration</h3><p>NCT05320094</p></div>","PeriodicalId":7652,"journal":{"name":"American Journal of Cardiovascular Drugs","volume":"24 4","pages":"569 - 575"},"PeriodicalIF":2.8,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11233281/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141454655","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}