Cardiovascular Drugs and Therapy最新文献

{"title":"Reassessing Ivabradine: Potential Benefits and Risks in Atrial Fibrillation Therapy.","authors":"Dorsa Alijanzadeh, Shahrzad Moghim, Paniz Zarand, Mohammad Ali Akbarzadeh, Yasaman Zarinfar, Isa Khaheshi","doi":"10.1007/s10557-024-07652-3","DOIUrl":"https://doi.org/10.1007/s10557-024-07652-3","url":null,"abstract":"<p><strong>Background: </strong>Ivabradine has been identified as a funny current (If) inhibitor in the sinoatrial node (SAN) and is considered an advocated therapeutic agent in chronic heart failure and stable angina. This therapeutic agent has shown positive benefits in maintaining a reduction in heart rate while sustaining hemodynamic stability. Its clinical application is still evolving and the mechanism of action is becoming clearer daily. The use of this agent to manage atrial fibrillation (AF) has recently been brought under discussion. This study summarizes the mechanism of action of ivabradine and current evidence about the risk of new-onset AF and rate-lowering potential as a therapeutic option in patients suffering from AF.</p><p><strong>Methods: </strong>This review synthesizes findings from preclinical studies, case reports, and clinical trials that assess ivabradine's efficacy in controlling heart rate and its association with new-onset AF.</p><p><strong>Results: </strong>Studies have shown that this medication may be beneficial in ventricular rate reduction in patients intolerant of first-line AF therapeutic options, including non-dihydropyridine calcium channel blockers and β-blockers. However, it is important to state that ivabradine-treated patients with cardiovascular diseases demonstrated an increased risk for new-onset AF compared with those patients who did not receive it.</p><p><strong>Conclusion: </strong>While ivabradine demonstrates promise as a therapeutic option for rate control in patients with AF, its use is accompanied by a notable risk of new-onset AF. Further studies should focus on optimal dosing strategies and long-term outcomes of ivabradine treatment in AF management.</p>","PeriodicalId":9557,"journal":{"name":"Cardiovascular Drugs and Therapy","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142799436","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":"Cytochrome P450-derived Epoxyeicosatrienoic Acid, the Regulation of Cardiovascular-related Diseases, and the Implication for Pulmonary Hypertension.","authors":"Run Lan, Meng-Jie Zhang, Ke Liu, Fang-Fang Meng, Xiao-He Xu, Chen-Chen Wang, Meng-Qi Zhang, Yi Yan, Jie-Jian Kou, Lu-Ling Zhao, Yang-Yang He, Hong-Da Zhang","doi":"10.1007/s10557-024-07655-0","DOIUrl":"https://doi.org/10.1007/s10557-024-07655-0","url":null,"abstract":"<p><p>Cytochrome P450 (CYP) epoxygenases metabolize arachidonic acid (AA) into biologically active epoxyeicosatrienoic acids (EETs), forming a pivotal metabolic pathway (AA-CYP-EETs-soluble epoxide hydrolase-dihydroxyeicosatrienoic acids) implicated in the progression of various disorders. Inflammation is a key contributor to the onset and progression of numerous systemic diseases, and EETs play a significant role in mitigating inflammation. Extensive research highlights the cardiovascular protective effects of EETs, which include vasodilation, anti-hypertensive, and anti-atherosclerotic properties. Interestingly, the relatively less-explored third metabolic pathway of AA exhibits both pro-proliferative and anti-apoptotic effects in endothelial cells and smooth muscle cells. Recent studies have shown elevated levels of EETs catalyzed by CYP epoxygenases in human tumors, promoting tumor progression and metastasis-phenomena closely related to the disease progression in pulmonary hypertension (PH). This review explores the current understanding of the regulatory functions of CYP-derived EETs in cardiovascular diseases and seeks to elucidate their potential implications in PH. Ultimately, understanding the multifaceted roles of EETs may help identify novel therapeutic targets for both cardiovascular diseases and PH.</p>","PeriodicalId":9557,"journal":{"name":"Cardiovascular Drugs and Therapy","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142799505","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":"Ferroptosis in Cardiovascular Diseases and Ferroptosis-Related Intervention Approaches.","authors":"Xianpeng Zhou, Hao Wang, Biao Yan, Xinwen Nie, Qingjie Chen, Xiaosong Yang, Min Lei, Xiying Guo, Changhan Ouyang, Zhanhong Ren","doi":"10.1007/s10557-024-07642-5","DOIUrl":"https://doi.org/10.1007/s10557-024-07642-5","url":null,"abstract":"<p><strong>Objective: </strong>Cardiovascular diseases (CVDs) are major public health problems that threaten the lives and health of individuals. The article has reviewed recent progresses about ferroptosis and ferroptosis-related intervention approaches for the treatment of CVDs and provided more references and strategies for targeting ferroptosis to prevent and treat CVDs.</p><p><strong>Methods: </strong>A comprehensive review was conducted using the literature researches.</p><p><strong>Results and discussion: </strong>Many ferroptosis-targeted compounds and ferroptosis-related genes may be prospective targets for treating CVDs and our review provides a solid foundation for further studies about the detailed pathological mechanisms of CVDs.</p><p><strong>Conclusion: </strong>There are challenges and limitations about the translation of ferroptosis-targeted potential therapies from experimental research to clinical practice. It warrants further exploration to pursure safer and more effective ferroptosis-targeted thereapeutic approaches for CVDs.</p>","PeriodicalId":9557,"journal":{"name":"Cardiovascular Drugs and Therapy","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142784271","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":"Investigating Sodium-Glucose Cotransporter 2 Inhibitors Versus Other Glucose-Lowering Drugs on Ventricular Arrhythmias or Sudden Cardiac Death Using the US FDA Adverse Event Reporting System.","authors":"Bo Xu, Tianqiao Zhang, Bo Kang, Xiongwen Yang, Shaoqian Li, Jixiang Chen, Zunbo He, Jiecan Zhou","doi":"10.1007/s10557-024-07653-2","DOIUrl":"https://doi.org/10.1007/s10557-024-07653-2","url":null,"abstract":"<p><strong>Purpose: </strong>Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been reported to exhibit antiarrhythmic effects. However, there is conflicting evidence regarding the association between SGLT2 inhibitors and ventricular arrhythmias or sudden cardiac death (SCD). We utilized the US FDA Adverse Event Reporting System (FAERS) database to investigate the reporting frequencies of SGLT2 inhibitors with ventricular arrhythmias and SCD compared to other glucose-lowering drugs (ATC-A10B).</p><p><strong>Methods: </strong>We used the web data mining tool AERSMine to mine reports of ventricular arrhythmias and SCD from FAERS to compare SGLT2 inhibitors versus other glucose-lowering drugs. The mining range was from 2004q1 to 2023q3. Disproportionality analysis used the proportional reporting ratio (PRR) with 95% confidence interval (CI) and information component (IC) with 95% credible interval.</p><p><strong>Results: </strong>From 2004q1 to 2023q3, a total of 121,129 adverse events were reported for SGLT2 inhibitors, with a total of 1,127,485 in the ATC-A10B group. Ventricular arrhythmias reporting frequency in the SGLT2 inhibitors group was similar to that of the control group (1.36/1000 reports vs 1.55/1000 reports; p = 0.10), with a PRR of 0.88 (95%CI 0.75-1.03). However, the reporting frequency of SCD in the SGLT2 inhibitors group was significantly lower than that of the control group (1.43 vs 4.70/1000; p < 0.001), with a PRR of 0.30 (95%CI 0.26-0.35), and this trend was observed within individual molecules of SGLT2 inhibitors. During the sensitivity analysis process, the results obtained when restricting the scope of data mining to between 2013q1 and 2023q3 were similar to those obtained when using data from 2004q1 to 2023q3.</p><p><strong>Conclusion: </strong>In this drug pharmacovigilance assessment, the reporting frequency of ventricular arrhythmias associated with SGLT2 inhibitors was similar to that of other antidiabetic medications, while the reporting frequency of SCD related to SGLT2 inhibitors was lower. This real-world study evidence complements existing clinical evidence.</p>","PeriodicalId":9557,"journal":{"name":"Cardiovascular Drugs and Therapy","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142766563","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":"CTRP5 Attenuates Doxorubicin-Induced Cardiotoxicity Via Inhibiting TLR4/NLRP3 Signaling.","authors":"Zhaoxia Zhang, Jianye Peng, Yewen Hu, Gaofeng Zeng, Weiping Du, Caijie Shen","doi":"10.1007/s10557-023-07464-x","DOIUrl":"10.1007/s10557-023-07464-x","url":null,"abstract":"<p><strong>Background: </strong>C1q/tumor necrosis factor-related protein 5 (CTRP5) has been reported to be a crucial regulator in cardiac ischemia/reperfusion (I/R) injury. Nevertheless, the potential role of CTRP5 in doxorubicin (DOX)-induced cardiotoxicity and the potential mechanisms remain largely unclear.</p><p><strong>Methods: </strong>We overexpressed CTRP5 in the hearts using an adeno-associated virus 9 (AAV9) system through tail vein injection. C57BL/6 mice were subjected to DOX (15 mg/kg/day, i.p.) to generate DOX-induced cardiotoxicity for 4 weeks. Subsequently, cardiac staining and molecular biological analysis were performed to analyze the morphological and biochemical effects of CTRP5 on the cardiac injury. H9c2 cells were used for validation in vitro.</p><p><strong>Results: </strong>CTRP5 expression was down-regulated after DOX treatment both in vivo and in vitro. CTRP5 overexpression significantly attenuated DOX-induced cardiac injury, cardiac dysfunction, inhibited oxidative stress and inflammatory response. Mechanistically, CTRP5 overexpression markedly decreased the protein expression of toll-like receptor 4 (TLR4), NLRP3, cleaved caspase-1 and caspase-1, indicating TLR/NLRP3 signaling contributes to the cardioprotective role of CTRP5 in DOX-induced cardiotoxicity.</p><p><strong>Conclusions: </strong>Together, our findings demonstrated that CTRP5 overexpression could protect the heart from oxidative stress and inflammatory injury induced by DOX through inhibiting TLR4/NLRP3 signaling, suggesting that CTRP5 might be a potential therapeutic target in the prevention of DOX-induced cardiotoxicity.</p>","PeriodicalId":9557,"journal":{"name":"Cardiovascular Drugs and Therapy","volume":" ","pages":"1235-1244"},"PeriodicalIF":3.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9551942","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":"The Efficacy and Safety of Patiromer for Heart Failure Patients: A Systematic Review and Meta-Analysis.","authors":"Yuhui Wang, Yu Gao, Jun Feng, Linlin Hou, Chunmiao Luo, Zhipeng Zhang","doi":"10.1007/s10557-023-07473-w","DOIUrl":"10.1007/s10557-023-07473-w","url":null,"abstract":"<p><strong>Purpose: </strong>To evaluate the efficacy and safety of patiromer, a novel potassium binder, in reducing the risk of hyperkalemia in patients with heart failure and optimizing their RAASi therapy.</p><p><strong>Design: </strong>Systematic review and meta-analyses.</p><p><strong>Method: </strong>The authors conducted a systematic search in Pubmed, Embase, Web of Science, and Cochrane Library for randomized controlled trials investigating the efficacy and safety of patiromer in heart failure patients from inception to 31 January 2023 and updated on 25 March 2023. The primary outcome was the association between the reduction of hyperkalemia and patiromer compared with placebo, and the secondary outcome was the association between optimization of RAASi therapy and patiromer.</p><p><strong>Results: </strong>A total of four randomized controlled trials (n = 1163) were included in the study. Patiromer was able to reduce the risk of hyperkalemia in heart failure patients by 44% (RR 0.56, 95% CI 0.36 to 0.87; I² = 61.9%), improve tolerance to target doses of MRA in patients with heart failure (RR 1.15, 95% CI 1.02 to 1.30; I² = 49.4%), and decrease the proportion of all-cause discontinuation of RAASi (RR 0.49, 95% CI 0.25 to 0.98; I² = 48.4%). However, patiromer therapy was associated with an increased risk of hypokalemia (RR 1.51, 95% CI 1.07 to 2.12; I² = 0%), while no other statistically significant adverse events were observed.</p><p><strong>Conclusion: </strong>Patiromer appears to have a considerable effect on reducing the incidence of hyperkalemia in heart failure patients and on optimizing the therapy of RAASi in those patients.</p>","PeriodicalId":9557,"journal":{"name":"Cardiovascular Drugs and Therapy","volume":" ","pages":"1245-1257"},"PeriodicalIF":3.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11680614/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9586728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insight into Cardioprotective Effects and Mechanisms of Dexmedetomidine.","authors":"Leyu Jiang, Wei Xiong, Yuqiao Yang, Jinqiao Qian","doi":"10.1007/s10557-024-07579-9","DOIUrl":"10.1007/s10557-024-07579-9","url":null,"abstract":"<p><strong>Purpose: </strong>Cardiovascular disease remains the leading cause of death worldwide. Dexmedetomidine is a highly selective α2 adrenergic receptor agonist with sedative, analgesic, anxiolytic, and sympatholytic properties, and several studies have shown its possible protective effects in cardiac injury. The aim of this review is to further elucidate the underlying cardioprotective mechanisms of dexmedetomidine, thus suggesting its potential in the clinical management of cardiac injury.</p><p><strong>Results and conclusion: </strong>Our review summarizes the findings related to the involvement of dexmedetomidine in cardiac injury and discusses the results in the light of different mechanisms. We found that numerous mechanisms may contribute to the cardioprotective effects of dexmedetomidine, including the regulation of programmed cell death, autophagy and fibrosis, alleviation of inflammatory response, endothelial dysfunction and microcirculatory derangements, improvement of mitochondrial dysregulation, hemodynamics, and arrhythmias. Dexmedetomidine may play a promising and beneficial role in the treatment of cardiovascular disease.</p>","PeriodicalId":9557,"journal":{"name":"Cardiovascular Drugs and Therapy","volume":" ","pages":"1139-1159"},"PeriodicalIF":3.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141310136","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":"Impact of CYP2C19 Genotype on Efficacy and Safety of Clopidogrel-based Antiplatelet Therapy in Stroke or Transient Ischemic Attack Patients: An Updated Systematic Review and Meta-analysis of Non-East Asian Studies.","authors":"Sarah Cargnin, Federica Ferrari, Salvatore Terrazzino","doi":"10.1007/s10557-023-07534-0","DOIUrl":"10.1007/s10557-023-07534-0","url":null,"abstract":"<p><strong>Purpose: </strong>Inconclusive and limited results have been reported on the clinical utility of CYP2C19 genotyping in stroke/TIA patients of non-East Asian ancestries. We herein performed an updated systematic review and meta-analysis to quantitatively estimate the association of CYP2C19 loss-of function (LOF) status with efficacy and safety of clopidogrel-based antiplatelet therapy in non-East Asian patients affected by stroke or TIA.</p><p><strong>Methods: </strong>A comprehensive search was performed up to July 2023 using PubMed, Web of Knowledge, and Cochrane Library databases. The clinical outcomes investigated were stroke, composite vascular events and bleeding. Pooled estimates were calculated as risk ratios (RR) with 95% CI using the Mantel- Haenszel random-effects model. The quality of evidence was assessed using the GRADEpro tool.</p><p><strong>Results: </strong>A total number of 1673 stroke/TIA patients from 8 non-East Asian studies, published between 2014 and 2022, were included in the systematic review. Clopidogrel-treated carriers of CYP2C19 LOF alleles were found at increased risk of stroke compared to non-carriers (RR: 1.68, 95%CI: 1.04-2.71, P = 0.03). However, no significant association was observed with the risk of composite vascular events (RR: 1.15, 95%CI: 0.58-2.28, P = 0.69) or bleeding (RR: 0.84, 95%CI: 0.38-1.86, P = 0.67). Similarly, European ancestry patients carrying CYP2C19 LOF alleles displayed a higher risk of stroke (RR: 2.69 (1.11-6.51, P = 0.03), but not of composite vascular events or bleeding.</p><p><strong>Conclusion: </strong>The present updated meta-analysis provides moderate quality evidence of association between CYP2C19 LOF alleles and an increased risk of stroke in non-East Asian patients with stroke/TIA after receiving clopidogrel therapy. Further large pharmacogenetic studies are still warranted to corroborate these findings.</p>","PeriodicalId":9557,"journal":{"name":"Cardiovascular Drugs and Therapy","volume":" ","pages":"1397-1407"},"PeriodicalIF":3.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11680632/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138458090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Clinical Efficacy and Safety of Bempedoic Acid in Patients at Elevated Risk of Cardiovascular Disease: A Meta-Analysis of Randomized Clinical Trials.","authors":"Ahmed Sayed, Omar Shazly, Leandro Slipczuk, Chayakrit Krittanawong, Farhala Baloch, Salim S Virani","doi":"10.1007/s10557-023-07474-9","DOIUrl":"10.1007/s10557-023-07474-9","url":null,"abstract":"<p><strong>Purpose: </strong>Statins are first-line agents to reduce low-density lipoprotein cholesterol (LDL-C) and cardiovascular risk, however, they are insufficient and/or intolerable in many patients. To that end, we conducted a meta-analysis of Bempedoic Acid (BA), a novel LDL-C lowering agent.</p><p><strong>Methods: </strong>We retrieved randomized clinical trials (RCTs) of BA by searching Pubmed, the Cochrane Central Register of Controlled Trials, and Clinicaltrials.gov. We used the Mantel-Haenszel method to pool estimates. The I² measure was used to quantify heterogeneity. Treatment effects are provided as relative risks (RR), absolute risk differences (ARD), and number needed to treat/harm (NNTB/H). Analyses were conducted using R, version 4.1.2.</p><p><strong>Results: </strong>11 trials enrolling 18,496 patients were included. Compared to placebo, BA reduced the risk of major adverse cardiovascular events (RR: 0.87; 95% CI: 0.80 to 0.95; ARD: -1.63%; NNT: 62), myocardial infarction (RR: 0.76; 95% CI: 0.66 to 0.89; ARD: -1.03%; NNT: 98), unstable angina hospitalization (RR: 0.70; 95%: CI: 0.55 to 0.89; ARD: -0.57%; NNT: 177), revascularization (RR: 0.81; 95% CI: 0.72 to 0.91; ARD: -1.31%; NNT: 77), and myalgia (RR: 0.85; 95% CI: 0.75 to 0.95; ARD: -0.99%; NNT: 102). BA significantly increased the risk of gout (RR: 1.56; 95% CI: 1.27 to 1.91; ARD: 0.99%; NNH: 101), renal impairment (RR: 1.35; 95% CI: 1.22 to 1.49; ARD: 2.54%; NNH: 40), and cholelithiasis (RR: 1.87; 95% CI: 1.43 to 2.44; ARD: 1.01%; NNH: 100).</p><p><strong>Conclusion: </strong>BA effectively reduces the risk of cardiovascular events and myalgia but increases the risk of gout, cholelithiasis, and renal impairment.</p>","PeriodicalId":9557,"journal":{"name":"Cardiovascular Drugs and Therapy","volume":" ","pages":"1415-1420"},"PeriodicalIF":3.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11680617/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9554557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mutant CYP3A4/5 Correlated with Clinical Outcomes by Affecting Rivaroxaban Pharmacokinetics and Pharmacodynamics in Patients with Atrial Fibrillation.","authors":"Xiaoye Li, Zhichun Gu, Zi Wang, Qing Xu, Chunlai Ma, Qianzhou Lv","doi":"10.1007/s10557-023-07495-4","DOIUrl":"10.1007/s10557-023-07495-4","url":null,"abstract":"<p><strong>Purpose: </strong>This study was designed to investigate the impact of single-nucleotide polymorphism-encoded cytochrome P450 enzymes (CYP3A4/5) on clinical outcomes of rivaroxaban in patients with non-valvular atrial fibrillation (NVAF) based on pharmacokinetics and pharmacodynamics (PK/PD) aspects.</p><p><strong>Method: </strong>A prospective study enrolling 165 rivaroxaban-treated patients with NVAF was conducted. Genotyping of CYP3A4 (rs2242480, rs2246709, rs3735451, and rs4646440) and CYP3A5 (rs776746) was performed to explore their impact on the trough plasma concentrations (C_trough) of rivaroxaban, coagulation indicators at the C_trough including activated partial thromboplastin time (APTT) and prothrombin time (PT), and clinical outcomes.</p><p><strong>Results: </strong>Patients with mutant genotype CYP3A4 (rs2242480, rs2246709, and rs3735451) and CYP3A5 (rs776746) had higher levels of rivaroxaban C_trough, PT values than that of wild-type. Furthermore, a positive relationship was revealed between C_trough and PT (r = 0.212, p = 0.007), while no significant correlation was found between C_trough and APTT. Regarding the clinical outcomes, the minor allele carriers on rs3735451 and the minor allele (A) carriers on rs2246709 were associated with higher incidence of minor bleeding (p = 0.028 and p = 0.038, respectively) and were identified as the independent risk factors of minor bleeding treated with rivaroxaban (p = 0.024 and p = 0.036, respectively), with the receiver operating characteristic (ROC) curve validated (AUC = 0.8956, 95% CI: 0.829-0.962).</p><p><strong>Conclusion: </strong>The CYP3A4 polymorphisms (rs2242480, rs2246709, and rs3735451) and CYP3A5 rs776746 were associated with variations in rivaroxaban PK/PD. The minor allele (C) carriers on rs3735451 and the minor allele (A) carriers on rs2246709 were correlated with clinical outcomes.</p>","PeriodicalId":9557,"journal":{"name":"Cardiovascular Drugs and Therapy","volume":" ","pages":"1315-1325"},"PeriodicalIF":3.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9931912","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}