Journal of atherosclerosis and thrombosis最新文献

{"title":"A Cost-Effectiveness Analysis for the Combination of Universal Screening at 9-10 Years Old and Reverse Cascade Screening of Relatives for Familial Hypercholesterolemia in Japan.","authors":"Keiji Matsunaga, Mariko Harada-Shiba, Shizuya Yamashita, Hayato Tada, Akihito Uda, Katsuya Mori, Mizuki Yoshimura, Sachie Inoue, Isao Kamae, Shinji Yokoyama, Tetsuo Minamino","doi":"10.5551/jat.65181","DOIUrl":"https://doi.org/10.5551/jat.65181","url":null,"abstract":"<p><strong>Aim: </strong>Screening for familial hypercholesterolemia (FH) is important for reducing the incidence of cardiovascular diseases (CVDs). Cost-effectiveness was evaluated using the Kagawa FH screening model, which is a combination of universal screening (US) in the universal health examination for children 9-10 years old conducted in Kagawa Prefecture, and reverse cascade screening (RCS) of the probands' relatives.</p><p><strong>Methods: </strong>A lifetime simulation was conducted using mathematical models (decision tree and Markov model) to determine the cost-effectiveness of introducing a series of FH screenings (US in children + RCS in adult relatives). Only screening-related costs and direct medical costs were included, using quality-adjusted life years (QALYs) as an outcome. The costs of statins were estimated using the public health insurance claims database DeSC Healthcare, Inc. The risk of each CVD event was estimated using the same claims data and adjusted for age. We hypothesized that standard statin treatment decreases CVD risk by reducing plasma low-density lipoprotein cholesterol levels.</p><p><strong>Results: </strong>A series of FH screenings (US in children + RCS in adult relatives) was cost-effective compared to no screening, with an incremental cost-effectiveness ratio (ICER) of approximately JPY 150,000 (USD 1,042)/QALY, which was below the willingness-to-pay threshold of JPY 5,000,000 (USD 34,722)/QALY for medical technology in Japan (USD 1 = JPY 144). The ICER for the US without RCS was also acceptable at approximately JPY 2,720,000 (USD 18,889)/QALY.</p><p><strong>Conclusion: </strong>The cost-effectiveness analysis revealed that a series of FH screenings (US in children + RCS in adult relatives) based on the Kagawa model was cost-effective.</p>","PeriodicalId":15128,"journal":{"name":"Journal of atherosclerosis and thrombosis","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143433222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preconditioning Effects of Neuromuscular Electrical Stimulation in Patients with Symptomatic Peripheral Arterial Disease.","authors":"Kyosuke Ehara, Yuma Tamura, Harunori Takahashi, Masato Terashima, Momo Takahashi, Tomoki Tsurumi, Hiroyuki Sugimura, Naoyuki Otani, Takashi Tomoe, Keijiro Kitahara, Takushi Sugiyama, Takanori Yasu","doi":"10.5551/jat.65490","DOIUrl":"https://doi.org/10.5551/jat.65490","url":null,"abstract":"<p><strong>Aims: </strong>Intermittent claudication is a major barrier to establishing an exercise routine in patients with peripheral artery disease (PAD). This study investigated the preconditioning effects of neuromuscular electrical stimulation (NMES) on walking capacity in patients with PAD and intermittent claudication. Additionally, it aimed to determine the optimal NMES settings and the underlying mechanisms of its effects.</p><p><strong>Methods: </strong>A total of 15 patients with PAD (Fontaine II) participated in a crossover study. Each patient underwent 10-min sessions of NMES at two frequencies (4 and 20 Hz) and two intensities (moderate and high), plus a sham condition, before treadmill walking tests using the modified Gardner protocol.</p><p><strong>Results: </strong>Pain-free walking distance significantly increased after a single session of 20 Hz high-intensity NMES (259.2±27.5 m; p＜0.05) relative to the sham group (201.9±23.6 m). The maximum walking distance also improved significantly after 4 and 20 Hz high-intensity NMES. The vascular endothelial function, assessed by flow-mediated dilation, was significantly enhanced following 20 Hz moderate- and high-intensity NMES, as well as 4 Hz high-intensity NMES, relative to the sham group. Additionally, lower extremity blood flow, as measured via transcutaneous partial pressure of oxygen, improved significantly in all NMES conditions. However, serum markers such as myeloperoxidase, hepatocyte growth factor, vascular endothelial growth factor, and CD34^＋/CD133^＋ progenitor cell counts did not differ significantly between the NMES and sham groups.</p><p><strong>Conclusion: </strong>High-intensity 20 Hz NMES is an effective preconditioning strategy for instantaneously enhancing the walking capacity in patients with PAD, likely due to nitric oxide-mediated vasodilation. These findings suggest that NMES is a promising therapeutic approach for PAD rehabilitation.</p>","PeriodicalId":15128,"journal":{"name":"Journal of atherosclerosis and thrombosis","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143408046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-Term Effects of Extended-Release Pemafibrate Tablets on Dyslipidemia and Safety in Triglyceridemic Patients: A Phase 3, Multicenter, Randomized, Open-Label, Parallel-Group Study.","authors":"Hidenori Arai, Shizuya Yamashita, Eiichi Araki, Koutaro Yokote, Ryohei Tanigawa, Ayumi Saito, Daisuke Furukawa, Hideki Suganami, Shun Ishibashi","doi":"10.5551/jat.65350","DOIUrl":"https://doi.org/10.5551/jat.65350","url":null,"abstract":"<p><strong>Aims: </strong>Long-term safety and efficacy of pemafibrate once-daily extended-release (XR) tablets, taken in morning or evening, were evaluated in dyslipidemic patients with high triglycerides (TG).</p><p><strong>Methods: </strong>In this multicenter, randomized, open-label, parallel-group, phase 3 long-term study, dyslipidemic patients with high TG were randomly assigned to morning or evening administration of XR for 52 weeks. The dose was started at 0.2 mg/day and increased to 0.4 mg/day for patients having fasting serum TG ≥ 150mg/dL during treatment. The primary efficacy endpoint was percent change in fasting serum TG.</p><p><strong>Results: </strong>The study enrolled 121 patients, assigning 61 to morning and 60 to evening administration. The study population included 71.1% males. Mean age was 58.5±11.1 (mean±SD) years, body mass index 27.7±4.3 kg/m², and fasting TG 264.0±109.2 mg/dL. Fasting serum TG decreased significantly from baseline to 52 weeks among patients overall and in the morning and evening groups (-45.7%, -44.8%, and -46.6%, respectively, p＜0.001 vs. baseline). The difference in least-squares mean between the morning and evening groups was 3.0%, not statistically significant. The dose was increased in 82 patients (44 morning and 38 evening), with 57.3% (95%CI 45.9, 68.2) achieving fasting serum TG ＜150 mg/dL. Adverse events occurred in 83.5% and adverse drug reactions in 19.0% but with no notable safety problems.</p><p><strong>Conclusions: </strong>Long-term, once-daily administration of XR was effective and safe in dyslipidemic patients with high TG. XR provided favorable TG-lowering effects regardless of morning or evening administration, and the XR dose increase proved effective in patients having initially inadequate response.</p>","PeriodicalId":15128,"journal":{"name":"Journal of atherosclerosis and thrombosis","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143382493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Genetic Risk Score with Variants in PDGFs and PDGFRB for the Risk of Major Cardiovascular Adverse Events in Patients with Coronary Artery Disease.","authors":"Xiaojuan Xu, Wen Li, Fangyuan Liu, Changying Chen, Hankun Xie, Feifan Wang, Xu Han, Qian Zhuang, Xianghai Zhao, Junxiang Sun, Yunjie Yin, Pengfei Wei, Yanchun Chen, Song Yang, Chong Shen","doi":"10.5551/jat.65369","DOIUrl":"https://doi.org/10.5551/jat.65369","url":null,"abstract":"<p><strong>Aims: </strong>Previous studies have linked platelet-derived growth factors (PDGFs) and their receptor beta (PDGFRB) genetic variants to coronary artery disease (CAD), but their impact on major adverse cardiovascular events (MACEs) remains unclear.</p><p><strong>Methods: </strong>A cohort study of 3139 patients with CAD followed up until December 1, 2022 (median 5.42 years), genotyped 13 tagSNPs in PDGFs/PDGFRB pathway genes to establish weighted genetic risk scores (wGRS). Multiple Cox regression models analyzed the association of SNPs and wGRS with MACE outcomes using hazard ratios (HRs) and 95% confidence intervals (CIs). The wGRS improvement on traditional risk factors (TRFs) and the Global Registry of Acute Coronary Events (GRACE) score for MACEs were assessed using the C-statistic, net reclassification improvement (NRI), and integrated discrimination improvement (IDI).</p><p><strong>Results: </strong>Compared to low MACE-GRS (Q1 of quintile), high MACE-GRS (Q5 of quintile) had an increased risk of MACEs, with an adjusted HRs of 1.441 (P = 0.006). Compared to the TRF prediction model, the addition of MACE-GRS showed an improved discrimination with an NRI of 5.1% (95% CI, 0.7%-9.5%, P＜0.001) and IDI of 0.3% (95% CI, 0.0%-0.6%, P＜0.001). In addition, compared to the TRFs and GRACE score model, the addition of MACE-GRS showed an improved discrimination with an NRI of 5.1% (95% CI, 0.7%-9.6%, P＜0.001) and IDI of 0.3% (95% CI, 0.0%-0.5%, P＜0.001).</p><p><strong>Conclusions: </strong>Variants in the PDGF-PDGFRB pathway genes contribute to the risk of MACEs after CAD, and the wGRS might be able to serve as a risk predictor of MACEs in addition to TRFs.</p>","PeriodicalId":15128,"journal":{"name":"Journal of atherosclerosis and thrombosis","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143255736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transition of Metabolic Health Status and the Risk of Cardiovascular Diseases in a Japanese Population: the Hisayama Study.","authors":"Mayu Higashioka, Satoko Sakata, Emi Oishi, Takanori Honda, Mao Shibata, Jun Hata, Takanari Kitazono, Haruhiko Osawa, Toshiharu Ninomiya","doi":"10.5551/jat.65275","DOIUrl":"https://doi.org/10.5551/jat.65275","url":null,"abstract":"<p><strong>Aims: </strong>To investigate the association between metabolic health status, defined by the combination of metabolic syndrome (MetS) and obesity, and cardiovascular disease (CVD) in a Japanese community.</p><p><strong>Methods: </strong>A total of 2,842 participants without prior CVD, aged 40 years or older, were followed up from 2007 until 2017. Participants were classified into 4 metabolic health statuses based on the presence of obesity (body mass index ≥ 25 kg/m²) and MetS: metabolically healthy normal weight (MHN) (obesity [-] and MetS [-]), metabolically unhealthy normal weight (MUN) (obesity [-] and MetS [+]), metabolically healthy obesity (MHO) (obesity [+] and MetS [-]), and metabolically unhealthy obesity (MUO) (obesity [+] and MetS [+]). The risk estimates were computed by using a Cox hazard regression analysis.</p><p><strong>Results: </strong>During the follow-up period, 190 participants developed CVD. The MUO group had a 1.94-times greater risk of developing CVD than the MHN group after adjusting for confounders, but no excess risk was observed in the MHO group. Moreover, in 1,595 participants who had undergone a health checkup in 2002, 5 years before baseline, the risk of developing CVD was 2.18-times greater in the group that transitioned from MHO to MUO and 1.75-times higher in the stable MUO group than in the stable MHN group, but was not higher in the stable MHO group.</p><p><strong>Conclusions: </strong>The present findings suggest that cardiovascular risk increases when metabolic abnormalities are present simultaneously with obesity. In individuals with obesity, it may be important to maintain metabolic health and/or lose weight to prevent CVD.</p>","PeriodicalId":15128,"journal":{"name":"Journal of atherosclerosis and thrombosis","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143255747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteomic Analysis of Human Chylomicron Remnants Isolated by Apolipoprotein B-48 Immunoprecipitation.","authors":"Daisaku Masuda, Takeshi Okada, Masami Sairyou, Kazuaki Takafuji, Tohru Ohama, Masahiro Koseki, Makoto Nishida, Yasushi Sakata, Shizuya Yamashita","doi":"10.5551/jat.64920","DOIUrl":"10.5551/jat.64920","url":null,"abstract":"<p><strong>Aim: </strong>Postprandial hypertriglyceridemia (PHTG) is an independent risk factor for coronary heart diseases. PHTG exhibits accumulation of apoB-48 containing chylomicron remnants (CM-Rs) and apoB-100 containing VLDL remnants (VLDL-Rs), which are both known to be atherogenic. However, unlike VLDL-Rs, structural and functional characterization of CM-Rs remains to be elucidated due to challenges in separating CM-Rs from VLDL-Rs. Recently, we successfully isolated CM-Rs and VLDL-Rs utilizing anti-apoB-48 or apoB-100 specific antibodies. This study aimed to characterize the proteome of CM-Rs along with that of VLDL-Rs.</p><p><strong>Methods: </strong>Eight healthy subjects were enrolled. Venous blood was drawn 3 hours after high-fat-containing meals. We isolated CM-Rs and VLDL-Rs from sera through combination of ultracentrifugation and immunoprecipitation using apoB-48 or apoB-100 specific antibodies, followed by shotgun proteomic analysis.</p><p><strong>Results: </strong>We identified 42 CM-Rs or VLDL-Rs-associated proteins, including 11 potential newly identified proteins such as platelet basic protein (PPBP) and platelet factor 4, which are chemokines secreted from platelets. ApoA-I, apoA-IV, and clusterin, which are also known as HDL-associated proteins, were significantly more abundant in CM-Rs. Interestingly, apoC-I, which reduces the activity of lipoprotein lipase and eventually inhibits catabolism of remnant proteins, was also more abundant in CM-Rs. Moreover, we identified proteins involved in complement regulation such as complement C3 and vitronectin, and those involved in acute-phase response such as PPBP, serum amyloid A protein 2, and protein S100-A8, in both CM-Rs and VLDL-Rs.</p><p><strong>Conclusions: </strong>We have firstly characterized the proteome of CM-Rs. These findings may provide an explanation for the atherogenic properties of CM-Rs.</p>","PeriodicalId":15128,"journal":{"name":"Journal of atherosclerosis and thrombosis","volume":" ","pages":"226-238"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11802255/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141859840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Non-HDL-C, Symptomatic Intracranial Arterial Stenosis, and Recurrent Vascular Risk in Minor Stroke.","authors":"Haimei Fan, Tingting Liu, Kaili Zhang, Yongle Wang, Rong Wang, Fei Yang, Feifei Chen, Yanli Zhang, Huaai Guo, Xinyi Li, Xuemei Wu, Xiaoyuan Niu","doi":"10.5551/jat.64987","DOIUrl":"10.5551/jat.64987","url":null,"abstract":"<p><strong>Aim: </strong>We aimed to assess the association between non-high-density lipoprotein cholesterol (non-HDL-C) and symptomatic intracranial artery stenosis (sICAS), as well as the impact of non-HDL-C on recurrent vascular events in patients with mild ischemic stroke ( NIHSS score ≤ 5).</p><p><strong>Methods: </strong>This prospective study was based on data from patients presenting within 72 hours of stroke occurrence. We included patients admitted to 8 Chinese hospitals between September 2019 and November 2021. The associations of non-HDL-C with sICAS and recurrent vascular risk were assessed using multivariate regression models and a restricted cubic spline analysis.</p><p><strong>Results: </strong>Among the 2,544 patients analyzed at 12 months, 652 (25.6%) were diagnosed with sICAS. Elevated non-HDL-C was linked to a higher incidence of sICAS, and the adjusted odd ratios for quintile variables and continuous variables were 1.36 ([95% CI, 1.01-1.81]) and 1.14 ([95% CI, 1.04-1.24). In comparison to those in the first quintile, the adjusted hazard ratio of the fifth quintile of non-HDL-C was 1.19 ([95% CI 0.78-1.80]) for recurrent ischemic stroke and was 0.39 ([95% CI, 0.17-0.91]) for intracranialhemorrhage.</p><p><strong>Conclusions: </strong>The non-HDL-C level may be a useful predictor of sICAS. Higher non-HDL-C levels may be associated with a lower risk of intracranial hemorrhage in mild, noncardiogenic stroke, but not a higher risk of recurrent ischemic stroke.</p>","PeriodicalId":15128,"journal":{"name":"Journal of atherosclerosis and thrombosis","volume":" ","pages":"141-162"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11802245/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142132853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FIB-4 Index and Liver Stiffness Measurement are Potential Predictors of Atherosclerosis in Metabolic Dysfunction-Associated Steatotic Liver Disease.","authors":"Yoshihito Kubotsu, Yoshiko Sakamoto, Motoko Tago, Atsuko Chihara, Misa Norita, Chika Inadomi, Kaori Inoue, Hiroki Takayanagi, Kenichi Tanaka, Hiroshi Isoda, Takuya Kuwashiro, Satoshi Oeda, Toshiyasu Shiratori, Keizo Anzai, Koichi Node, Hirokazu Takahashi","doi":"10.5551/jat.64809","DOIUrl":"10.5551/jat.64809","url":null,"abstract":"<p><strong>Aims: </strong>Cardiovascular disease (CVD) is a common cause of death in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). Therefore, CVD surveillance is important, but it is not well established. We evaluated the association between liver fibrosis, carotid artery atherosclerosis, and coronary artery stenosis in patients with MASLD.</p><p><strong>Methods: </strong>Overall, 153 patients with MASLD who underwent carotid artery ultrasound were enrolled. Maximum intima-media thickness including plaques (Max-IMT) was measured by ultrasound. To predict liver fibrosis, liver stiffness was measured by vibration-controlled transient elastography and the fibrosis 4 (FIB-4) index was calculated. Coronary computed tomography angiography was performed to detect coronary artery stenosis based on a Max-IMT of ≥ 1.1 mm.</p><p><strong>Results: </strong>The median Max-IMT was 1.3 mm, and 63 patients (41.2%) had a Max-IMT of ≥ 1.5 mm. FIB-4 index and liver stiffness was significantly correlated with Max-IMT, respectively (ρ=0.356, p＜0.001, ρ=0.25, p=0.002). Liver stiffness was significantly associated with a Max-IMT of ≥1.5 mm, independent of age. Individuals with higher FIB-4 index had moderate or severe coronary artery stenosis more frequently. Individuals with higher LSM level also had moderate or severe coronary artery stenosis more frequently, especially severe stenosis.</p><p><strong>Conclusions: </strong>Liver fibrosis parameters were associated with carotid artery atherosclerosis and coronary artery stenosis. Evaluation of liver fibrosis may be useful to identify significant atherosclerosis and coronary artery stenosis in patients with MASLD.</p>","PeriodicalId":15128,"journal":{"name":"Journal of atherosclerosis and thrombosis","volume":" ","pages":"239-252"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11802251/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142132852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antiplatelets for Cardiovascular Disease in Non-valvular AF with Rivaroxaban: A Subanalysis of the EXPAND Study.","authors":"Koichi Kaikita, Shinichiro Uchiyama, Hirotsugu Atarashi, Hiroshi Inoue, Takanari Kitazono, Takeshi Yamashita, Wataru Shimizu, Takanori Ikeda, Masahiro Kamouchi, Koji Fukuda, Hideki Origasa, Hiroaki Shimokawa","doi":"10.5551/jat.64681","DOIUrl":"10.5551/jat.64681","url":null,"abstract":"<p><strong>Aim: </strong>In this subanalysis of the EXPAND study, we evaluated the risks and benefits of rivaroxaban plus antiplatelet therapy (APT) for patients with non-valvular atrial fibrillation (NVAF) complicated by stable coronary artery disease (CAD), ischemic stroke, or peripheral artery disease (PAD).</p><p><strong>Methods: </strong>From the EXPAND study population (n=7,141), patients with NVAF complicated by stable CAD (n=886), ischemic stroke (n=1,231), or PAD (n=160) were included. Patients complicated by any of them were set as ALL (n=2,030). Patients were all treated with rivaroxaban (10 or 15 mg/day) with (+) or without (-) APT. Efficacy outcomes were symptomatic stroke＋systemic embolism (SE), symptomatic stroke＋SE＋myocardial infarction＋cardiovascular death, and all-cause death. Safety outcomes included major and any bleeding. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated for differences between the APT(+) and APT(-) groups.</p><p><strong>Results: </strong>There were no significant differences in the efficacy outcomes between the APT(+) and APT(-) groups in the ALL cohort or in the CAD and STROKE sub-cohorts. In the PAD subcohort, the HR [95% CI] for all-cause death in the APT(+) group increased (4.43 [1.05-18.71]; p=0.043). In the APT(+) group, the HR [95% CI] for any bleeding increased in the ALL cohort (1.28 [1.01-1.62]; p=0.044) and STROKE subcohort (1.42 [1.01-2.01]; p=0.047), and for major bleeding in the CAD subcohort (2.00 [1.01-3.93]; p=0.046).</p><p><strong>Conclusions: </strong>Rivaroxaban with APT did not reduce ischemic outcomes in patients with stable CAD or ischemic stroke; however, it did increase the risk of bleeding in patients with stable CAD or ischemic stroke.</p>","PeriodicalId":15128,"journal":{"name":"Journal of atherosclerosis and thrombosis","volume":" ","pages":"176-187"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11802248/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142347240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacokinetics and Safety of Pemafibrate in Patients with both Dyslipidemia and Severe Renal Impairment: A Phase 4 Study.","authors":"Shun Ishibashi, Hidenori Arai, Koutaro Yokote, Eiichi Araki, Mao Watanabe, Michiko Nakanishi, Yuichi Makinose, Hideki Suganami, Yuji Kurihara, Shizuya Yamashita","doi":"10.5551/jat.64887","DOIUrl":"10.5551/jat.64887","url":null,"abstract":"<p><strong>Aims: </strong>Per the package insert, pemafibrate was contraindicated for use in patients with severe renal impairment despite its biliary excretion. To validate this, we evaluated the pharmacokinetics and safety of pemafibrate for 12 weeks in patients with hypertriglyceridemia and renal impairment.</p><p><strong>Methods: </strong>In this phase 4, multicenter, placebo-controlled, double-blind, parallel-group, comparative study, 21 patients were randomly assigned to pemafibrate 0.2 mg/day or placebo within Groups A (estimated glomerular filtration rate [eGFR] ＜30 mL/min/1.73m² without hemodialysis; pemafibrate n=4; placebo, n=2), B (hemodialysis; pemafibrate, n=4; placebo, n=1), and C (eGFR ≥ 30 and ＜60 mL/min/1.73m² without hemodialysis; pemafibrate, n=8; placebo, n=2) for 12 weeks. Area under the concentration vs time curve within the dosing interval (τ) (AUC_τ) of pemafibrate was measured after 12-week administration.</p><p><strong>Results: </strong>The AUC_τ (geometric mean) of pemafibrate was 7.333 and 7.991 ng·h/mL in Groups A+B and C, respectively; in Groups A+B to C at 12 weeks, the geometric mean ratio of pemafibrate AUC_τ was 0.92 (90% confidence interval [CI]: 0.62, 1.36). The upper limit of the 90% CI was ≤ 2.0 (predetermined criterion). There was no consistent trend in the AUC_τ and maximum plasma concentration of pemafibrate with/without statin use. Renal impairment degree did not affect the incidence of adverse events. No safety concerns were observed.</p><p><strong>Conclusion: </strong>Pemafibrate repeated administration in patients with severe renal impairment did not increase pemafibrate exposure.</p>","PeriodicalId":15128,"journal":{"name":"Journal of atherosclerosis and thrombosis","volume":" ","pages":"210-225"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11802250/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142132854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}