Journal of Cardiovascular Pharmacology最新文献

{"title":"Efficacy and Safety of Aspirin-free versus Aspirin-based Strategies in Patients With Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention: A Systematic Review and Meta-Analysis.","authors":"Misha Khan, Muhammad Ahmed Haroon Janjua, Syed Muhammad Muneeb Akhtar, Abdullah Al-Qaraghuli, Ali Saad Al-Shammari, Ahmed Sermed Al Sakini, Eesha Asghar Ali, Sadish Sharma, M Rafiqul Islam, Mohammedbaqer Ali Al-Ghuraibawi, Hashim Talib Hashim, Yasar Sattar","doi":"10.1097/FJC.0000000000001801","DOIUrl":"10.1097/FJC.0000000000001801","url":null,"abstract":"<p><strong>Abstract: </strong>Aspirin (ASA) is the cornerstone of the acute coronary syndrome primary and secondary prevention. Still, its role is debated in some high bleeding risk patients or cases that underwent second-generation drug-eluting stents with a better scaffold. This study compared the efficacy and safety of aspirin-free versus aspirin-based strategies in patients with ACS undergoing PCI. We systematically searched PubMed, Embase, Scopus, and ScienceDirect for studies comparing aspirin-based versus aspirin-free strategies in patients with ACS undergoing PCI. Pooled relative risk (RR) with 95% CI was calculated using a fixed effects model or a random effects model if heterogeneity was present. Significance was set at P < 0.05. Thirty studies including 207,938 patients (N = 104,062 in the ASA arm, and 103,876 in the ASA-free arm) were included in this study. There was a statistically significant reduction in risk of all-cause mortality [RR 0.93, 95% CI, 0.87-0.99, P-value = 0.024, I2 = 0%], BARC 2-5 [RR = 0.68, 95% CI, 0.58-0.81, P-value = <0.01, I2 = 0%], BARC 3 or 5 [RR= 0.71, 95% CI, 0.60-0.82, P-value= <0.01, I2 = 0%], TIMI major bleeding [RR = 0.66, 95% CI, 0.50-0.86, P-value= 0.02, I2 = 0%], TIMI minor or major bleeding [RR= 0.61, 95% CI, 0.52-0.72, P-value= <0.01, I2 = 0%], and ISTH major bleeding with aspirin-free strategy [RR= 0.52, 95% CI, 0.42-0.64, P-value= <0.001, I2= 0%]. Other secondary outcomes showed statistically nonsignificant results. The aspirin-free strategy showed lower all-cause mortality and bleeding, supporting its efficacy and safety in high bleeding risk patients.</p>","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":"87 4","pages":"209-218"},"PeriodicalIF":2.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147608949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and Safety of Oral PCSK9 Inhibitors in Adults With Hypercholesterolemia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.","authors":"Amna Amir Jalal, Syed Ibad Hussain, Erum Siddiqui, Muhammad Saad Khan, Muhammad Burhan, Ali Jawwad Karim, Rabia Nizam, Mahrukh Amir","doi":"10.1097/FJC.0000000000001789","DOIUrl":"10.1097/FJC.0000000000001789","url":null,"abstract":"<p><strong>Abstract: </strong>Injectable PCSK9 inhibitors effectively lower LDL-C levels in patients with hypercholesterolemia; however, their high cost and requirement for parenteral administration limit their widespread use. Oral PCSK9 inhibitors have emerged as a convenient alternative. This review and meta-analysis of the literature evaluate the effectiveness and safety of oral PCSK9 inhibitor treatment for adults with hypercholesterolemia. PubMed, Embase, Cochrane CENTRAL, and Scopus were searched through September 2025 for randomized controlled trials comparing oral PCSK9 inhibitors with placebo. The primary outcome was percentage change in LDL-C, with secondary lipid and safety outcomes. We used Cochrane RoB 2.0 tool to assess risk of bias, and pooled estimates were calculated using a random-effects model. Certainty of evidence was evaluated with GRADE. From 1253 records, 3 trials were included. Participants were mostly men, aged 61-65 years, with elevated baseline LDL-C. Oral PCSK9 inhibitors significantly reduced LDL-C and ApoB in a dose-dependent manner and achieved modest reductions in triglycerides (MD -6.56 mg/dL; 95% CI, -12.30 to -0.83) and total cholesterol (MD -25.25 mg/dL; 95% CI, -30.67 to -19.83). Effects on lipoprotein(a) were inconsistent. Adverse events (RR 1.06; 95% CI, 0.91-1.23) and serious adverse events (RR 1.32; 95% CI, 0.41-4.26) were comparable with placebo. According to our review, oral PCSK9 inhibitors are a promising therapeutic option for treating hypercholesterolemia because of their potent lipid-lowering effects and an overall favorable safety profile. However, more trials are needed to confirm their impact on cardiovascular outcomes.</p>","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":" ","pages":"219-228"},"PeriodicalIF":2.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145862747","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":"Cannabidiol Protects the Heart From Ischemia-Reperfusion Injury Through SIRT-1/PGC-1α Activation and Nuclear Factor Kappa B Modulation: Experimental Insights.","authors":"Fatih Aksoy, Mehtap Savran, Dincer Uysal, Ali Bagci, Ilter Ilhan, Orhan Imeci, Mehmet A Sevuk, Ozlem Ozmen, Muhammet Y Tepebasi, Halil Asci","doi":"10.1097/FJC.0000000000001806","DOIUrl":"10.1097/FJC.0000000000001806","url":null,"abstract":"<p><strong>Abstract: </strong>Myocardial ischemia-reperfusion (I/R) injury remains a major cause of acute cardiac dysfunction and is characterized by oxidative stress, inflammation, and apoptosis. Cannabidiol (CBD), a nonpsychoactive phytocannabinoid, has been reported to exert cardioprotective effects; however, its potential association with mitochondrial biogenesis-related signaling pathways remains incompletely understood. The aim of this study was to evaluate the cardioprotective potential of CBD in a rat myocardial I/R model and to investigate its possible association with SIRT-1/PGC-1α-related mitochondrial biogenesis and nuclear factor kappa B (NF-κB)-dependent inflammatory signaling. Forty rats were randomly assigned to 4 groups: sham, I/R, prophylactic CBD, and therapeutic CBD. Myocardial ischemia was induced by ligating the left anterior descending coronary artery for 30 minutes, followed by 30 minutes of reperfusion. Heart and aortic tissues were evaluated histopathologically, immunohistochemically, biochemically, and genetically to assess oxidative stress, inflammation, and mitochondrial biogenesis-related markers. The I/R group exhibited marked myocardial injury characterized by hyperemia, edema, hemorrhage, and inflammatory infiltration, accompanied by elevated levels of vascular cell adhesion molecule-1 (VCAM-1), vascular endothelial growth factor, and NF-κB. By contrast, SIRT-1, PGC-1α, and B-cell lymphoma 2 (Bcl-2) expression significantly declined, alongside increased total oxidant status and oxidative stress index. Prophylactic CBD treatment notably restored myocardial architecture, suppressed inflammatory and apoptotic responses, and enhanced mitochondrial biogenesis. Therapeutic CBD administration also provided partial protection. CBD confers robust cardioprotection against myocardial I/R injury by activating the SIRT-1/PGC-1α axis, promoting mitochondrial biogenesis, and attenuating oxidative, inflammatory, and apoptotic pathways. These findings indicated that it confers significant cardioprotection against myocardial IR injury and that this protective effect is associated with modulation of SIRT-1/PGC-1α-related mitochondrial biogenesis and NF-κB-dependent inflammatory signaling. Further mechanistic studies are warranted to establish definitive causal relationships.</p>","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":" ","pages":"270-282"},"PeriodicalIF":2.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146201784","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":"Integrating Network Pharmacology and In Vitro 3D Cardiac Organoid Model Validation to Investigate the Action Mechanism of Shenfu Xiangshao Decoction on Heart Failure.","authors":"Sijie Yao, Hui Zhang, Min Li, Shuo Han, Xinyue Ding, Xuan Zhao, Ting Dai, Jin Yang, Daying Wang, Lina Xing, Junqing Gao, Yanan Zhu, Zongjun Liu","doi":"10.1097/FJC.0000000000001802","DOIUrl":"10.1097/FJC.0000000000001802","url":null,"abstract":"<p><strong>Abstract: </strong>Heart failure (HF) represents a significant global public health challenge with profound implications for human health. Shenfu Xiangshao Decoction (SFXSD) is a commonly used adjuvant therapy for HF. However, its molecular mechanism remains unclear. This study aims to explore the core components, key targets, and potential mechanisms of SFXSD in the treatment of HF. Network pharmacology, molecular docking, and molecular dynamics simulations were used to identify the active compounds and targets of SFXSD. A 3D HF cardiac organoid model was developed using doxorubicin (DOX). Techniques such as Western blotting, TUNEL staining, ELISA, and Masson staining were performed to investigate the mechanisms of SFXSD. SFXSD acted on HF, comprising 126 active ingredients and 33 core cross-targets. The 4 principal effector components, quercetin, kaempferol, licochalcone A, and naringenin, could form stable complexes with the core target MAPK14 (p38 MAPK). In this study, we successfully constructed an HF cardiac organoid model using 10 μM DOX, on which the mechanism was validated. The results indicated that quercetin and kaempferol, the active ingredients of SFXSD, could ameliorate DOX-induced cardiac organoids apoptosis, inflammation, and fibrosis by reducing the expression of p38/ERK MAPK, BAX/BCL-2 ratio, the release of TNF-α, and IL-6. This in vitro 3D cardiac organoid model provides a valuable platform for drug screening and disease modeling, while the discovery of quercetin and kaempferol offers a solid theoretical basis for HF treatment.</p>","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":" ","pages":"283-298"},"PeriodicalIF":2.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13043231/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146258026","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":"Evidence of Cardiotoxic Immune Activation by Triple Immune Checkpoint Blockade: A Translational Alert for Clinical Surveillance in Patients With Cancer.","authors":"Vincenzo Quagliariello, Margherita Passariello, Martina Belardo, Assunta Esposito, Miriam Paone, Massimiliano Berretta, Martina Iovine, Matteo Barbato, Maria Laura Canale, Andrea Paccone, Alessandro Inno, Stefano Oliva, Carlo Maurea, Pietro Forte, Alfredo Mauriello, Celeste Fonderico, Giuseppina Gallucci, Luigi Tarantini, Massimiliano Camilli, Andrea Camerini, Claudia De Lorenzo, Nicola Maurea","doi":"10.1097/FJC.0000000000001798","DOIUrl":"10.1097/FJC.0000000000001798","url":null,"abstract":"<p><strong>Abstract: </strong>Immune checkpoint inhibitors (ICIs) have successfully revolutionized cancer therapy, but their immune-mediated adverse events include rare, often severe myocarditis. Although dual ICI blockade is associated with increased cardiotoxic risk, little is known about the potential effects of triplet combinations currently under clinical investigation. We developed a coculture model of human cardiomyocytes and human peripheral blood mononuclear cells (hPBMCs) to evaluate immune-mediated cytotoxicity induced by ICIs. HFCs were exposed for 48h to nivolumab plus relatlimab, ipilimumab, or atezolizumab, either alone or in triplet combinations. Cell lysis was quantified by LDH release. Cytokine secretion (IL-2, granzyme B, and additional inflammatory mediators including NLRP3 activation pathway) was measured by ELISA. Digital microscopy was used for morphological assessment. Triplet combinations of nivolumab-relatlimab with ipilimumab or atezolizumab induced significantly higher cardiomyocyte lysis than single agents or doublets ( P < 0.001). This effect correlated with a robust increase in IL-2 and granzyme B secretion, and activation of proinflammatory cytokines and NLRP3 inflammasome-related mediators. Microscopic analyses confirmed immune cell activation and reduced density of HFCs exposed to triplets. Our findings demonstrate that ICI triplets elicit potent immune activation against cardiomyocytes, providing the first preclinical evidence of direct cardiotoxic potential in this setting. These results highlight the need for enhanced clinical surveillance and cardio-oncology monitoring in patients receiving triple ICI combinations, because these regimens expand in clinical practice.</p>","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":" ","pages":"257-269"},"PeriodicalIF":2.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13043227/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146063616","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":"Lipid-Lowering Efficacy and Adverse Events of CETP Inhibitor Combination Therapy: A Systematic Review and Network Meta-Analysis.","authors":"Ping Guo, Xinlin Yu, Xinxin Wei, Xinlin Xiong, Jie Jiang","doi":"10.1097/FJC.0000000000001785","DOIUrl":"10.1097/FJC.0000000000001785","url":null,"abstract":"<p><strong>Background: </strong>The therapeutic effects of different combination therapies containing cholesteryl ester transfer protein (CETP) inhibitors vary. Evidence from head-to-head comparisons is scarce and inconsistent. This study aimed to evaluate the impact of CETP inhibitor-based combination therapy on lipid levels and explore its adverse events (AEs).</p><p><strong>Method: </strong>Randomized controlled trials (RCTs) were retrieved from PubMed, Embase, Cochrane Library, and Web of Science up to August 30, 2025. Thirteen RCTs were analyzed through STATA 14.0.</p><p><strong>Results: </strong>This systematic review and network meta-analysis of 13 studies (9248 participants) evaluated CETP inhibitor-based combination therapies. For HDL-C elevation, obicetrapib + ezetimibe + statin ranked highest (SUCRA = 95.1%). Evacetrapib + statin achieved reduction in LDL-C (SUCRA = 94.3%). Obicetrapib + ezetimibe + statin excelled in reducing TC (SUCRA = 100.0%) and TG (SUCRA = 99.9%). Obicetrapib + statin was most effective for ApoAI increase (SUCRA = 100.0%), while obicetrapib + ezetimibe + statin best reduced ApoB (SUCRA = 100.0%). Regarding safety, obicetrapib + statin had the optimal profile for all grade AEs (SUCRA = 19.2%) and severe AEs (SUCRA = 22.5%), conversely, evacetrapib + statin had the worst profile (SUCRA = 83.1% and 66.3%, respectively).</p><p><strong>Conclusions: </strong>Our meta-analysis demonstrated that CETP inhibitor combination therapies offer distinct lipid-modulating benefits and safety profiles. The obicetrapib + ezetimibe + statin triple therapy showed superior comprehensive efficacy, while obicetrapib + statin exhibited the optimal safety. Evacetrapib + statin provided potent LDL-C reduction but had the poorest safety. These findings facilitate personalized treatment selection for dyslipidemia management.</p><p><strong>Trial registration: </strong>PROSPERO CRD420251145396 ( https://www.crd.york.ac.uk/prospero/ ).</p>","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":" ","pages":"246-256"},"PeriodicalIF":2.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13043226/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145827690","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":"Role of the Gut Microbiome in Modulating Interactions Between β-Lactam Antibiotics and Statins in Coronary Heart Disease.","authors":"Guohui Wang, Yan Luo, Sangcang Song, Xingde Li, Yaping Pan, Zhongwen Zhao, Bo Wang, Qiongxiang Yang, Feng Yang, Tiantian Fang","doi":"10.1097/FJC.0000000000001805","DOIUrl":"10.1097/FJC.0000000000001805","url":null,"abstract":"<p><strong>Abstract: </strong>Clinical evidence suggests that the lipid-lowering efficacy of statins may be diminished by concurrent β-lactam administration in patients with coronary heart disease (CHD), yet the mechanisms driving this potential drug-drug interaction, particularly the role of gut microbiota as a mediator, remain undefined. To address this gap, we conducted a retrospective analysis of data from a tertiary hospital spanning 5 years, enrolling 436 patients with CHD on statin therapy who had 2 hospital admissions within a 3-month window. Patients were stratified into β-lactam-treated and antibiotic-free cohorts to assess the correlation between β-lactam exposure and statin efficacy. In addition, 16S ribosomal RNA gene sequencing was used to characterize and compare gut microbiota profiles between patients with CHD receiving combined rosuvastatin and β-lactam therapy versus those on rosuvastatin monotherapy. Our findings demonstrated that β-lactam exposure was associated with elevated low-density lipoprotein cholesterol and total cholesterol levels. Both rosuvastatin and β-lactams induced significant alterations in gut microbiota composition, with distinct shifts in bacterial taxa abundances: rosuvastatin increased the relative abundance of Faecalibacterium and Dysosmobacter , whereas β-lactams disrupted the abundance of Faecalibacterium , Roseburia , and Dysosmobacter . Collectively, these results indicate that concomitant β-lactam use impairs rosuvastatin efficacy in patients with CHD, likely through perturbation of gut microbiota composition. Rosuvastatin may exert a portion of its cardioprotective effects through modulation of gut microbiota, and β-lactams may abrogate this benefit by depleting key bacterial taxa linked to statin-mediated lipid regulation. Notably, Dysosmobacter emerges as a potential mediating species in this interaction, supporting a microbiome-dependent mechanism underlying the reduced lipid-lowering efficacy of rosuvastatin during β-lactam coadministration.</p>","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":" ","pages":"299-309"},"PeriodicalIF":2.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146213176","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":"Therapeutic Effects of PCSK9 Inhibitors on Lp(a)-Associated Atherosclerosis: Evidence and Perspectives.","authors":"Xinyan Li, Zhongsu Wang, Juan Liang, Bingsong Li, Qingxin Meng, Mei Gao","doi":"10.1097/FJC.0000000000001794","DOIUrl":"10.1097/FJC.0000000000001794","url":null,"abstract":"<p><strong>Abstract: </strong>Lipoprotein(a) [Lp(a)] is a genetically determined independent risk factor for atherosclerotic cardiovascular disease (ASCVD) that drives a significant residual risk through proatherogenic, proinflammatory, and prothrombotic pathways. However, current mainstay lipid-lowering therapies such as statins have limited efficacy in reducing Lp(a) levels, highlighting a critical therapeutic gap. This review aims to synthesize evidence on the role of Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) inhibitors in targeting Lp(a). We systematically searched PubMed and Embase for clinical trials and mechanistic studies (2010-2025), using the PRISMA and AMSTAR-2 frameworks to ensure methodological rigor and demonstrated that PCSK9 inhibitors (eg, alirocumab, evolocumab, and tafolecimab) not only reduced low-density lipoprotein (LDL-C) by 55%-60% but also lowered Lp(a) by 20%-30%. The efficacy of these agents varies ethnically, with tafolecimab showing superior performance in East Asian populations, which is partly attributable to the higher prevalence of the PCSK9 R46L loss-of-function allele. Mechanistically, PCSK9 inhibitors lowered Lp(a) levels through 2 pathways: suppression of hepatic synthesis and enhanced plasma clearance. This evidence supports the 2023 ESC guidelines, which issued a Class IIa recommendation for PCSK9 inhibitor use in patients with ASCVD and elevated Lp(a) levels. Given the evolving landscape, further research is warranted to confirm the role of these therapies in precision medicine paradigms for managing Lp(a)-associated risks.</p>","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":" ","pages":"229-241"},"PeriodicalIF":2.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146165836","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 Comparative Effects of S-Amlodipine Versus Racemic Amlodipine on Long-Term Cardiovascular Outcomes in Subjects With Hypertension: A Nationwide Population-Based Cohort Study.","authors":"Hack-Lyoung Kim, Bora Lee, Soojin Im","doi":"10.1097/FJC.0000000000001793","DOIUrl":"10.1097/FJC.0000000000001793","url":null,"abstract":"<p><strong>Abstract: </strong>Although S-amlodipine is known to have similar effects in lowering blood pressure and fewer side effects than amlodipine (= mixture of S- and R-amlodipine), there are no available data on its impact on long-term cardiovascular prognosis. This retrospective cohort study analyzed claims data from Korean subjects with hypertension treated with either S-amlodipine or amlodipine from 2010 to 2020. Subjects with history of cardiovascular disease or stroke were excluded. The composite end points of all-cause death, myocardial infarction, and stroke as 3P-major adverse cardiovascular event (MACE) and the composite end points of 3P-MACE and heart failure hospitalization as 4P-MACE were assessed. The study included 1:2 propensity score-matched groups of subjects taking S-amlodipine (n = 15,709) and amlodipine (n = 29,951). The mean clinical follow-up duration was 4.9 ± 0.3 years (median 5.0 years). After adjusting for clinical factors, S-amlodipine was associated with a reduced incidence of 3P-MACE (adjusted hazard ratio, 0.87; 95% confidence interval, 0.81-0.94; P < 0.001), and 4P-MACE (adjusted hazard ratio, 0.86; 95% confidence interval, 0.80-0.93; P < 0.001) compared with amlodipine. The better impact of S-amlodipine than amlodipine on 3P-MACE and 4P-MACE was also observed in the subgroup analysis based on various clinical factors. S-amlodipine showed better adherence than amlodipine (proportions of days covered ≥0.8: 96.7% vs. 91.8%; P < 0.001). In conclusion, S-amlodipine seems to potentially reduce the risk of long-term MACE compared with amlodipine in patients with hypertension who have no history of cardiovascular disease. However, these findings should be interpreted with caution and confirmed through further prospective studies.</p>","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":" ","pages":"201-208"},"PeriodicalIF":2.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146142496","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":"Dapagliflozin Reduces Myocardial Injuries Through Modulation of H3K27me3 and SIRT1 in the Male Rat Model of Myocardial Ischemia Reperfusion.","authors":"Tina Kianfar, Masoud Fallah, Fatemeh Ramezani, Kamran Rakhshan, Ebrahim Najafzadeh, Yaser Azizi","doi":"10.1097/FJC.0000000000001795","DOIUrl":"10.1097/FJC.0000000000001795","url":null,"abstract":"<p><strong>Abstract: </strong>Dapagliflozin (DAPA), a sodium-glucose cotransporter 2 (SGLT2) inhibitor, exhibits cardioprotective effects; however, the underlying epigenetic and molecular mechanisms remain poorly understood. This study investigated whether DAPA mitigates myocardial ischemia/reperfusion injury (MI/RI) by modulating enhancer of zeste homolog 2 (EZH2), trimethylation of lysine 27 on histone H3 (H3K27me3), and sirtuin 1 (SIRT1) expression. Wistar rats were randomly assigned to Sham, MI, and MI+DAPA groups (n = 12/group). MI groups underwent 30 minutes of left anterior descending coronary artery (LAD) ligation. For 14 days, animals in the MI+DAPA group received orally 1 mg/kg/day DAPA. Heart function, fibrosis, inflammatory factors (TNF-α, NF-κB, IL-1β, IL-6), and oxidative stress were assessed using echocardiography, Masson trichrome staining, Western blotting, and ELISA, respectively. EZH2, H3K27me3, and SIRT1 expression levels were also determined by Western blotting 14 days after MI induction. Tissue damage was evaluated using hematoxylin and eosin (H&E) staining. DAPA administration significantly improved MI-induced myocardial damage by decreasing serum levels of LDH, cTnI, and CK-MB. DAPA also improved left ventricular function by increasing ejection fraction (EF) and fractional shortening (FS), decreased left ventricular fibrosis, and reduced myocardial inflammation by improving myocardial TNF-α, NF-κB, IL-1β, and IL-6. In addition, DAPA reduced oxidative stress by decreasing malondialdehyde (MDA) levels and increasing superoxide dismutase (SOD) activity. Finally, DAPA downregulated EZH2, reducing H3K27me3 and subsequently increasing SIRT1 levels compared with the MI group. This study's results indicate that DAPA attenuates MI/RI in male rats by modulating epigenetic mechanisms, specifically through EZH2, and H3K27me3 suppression and SIRT1 upregulation, offering novel insights into its cardioprotective potential.</p>","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":" ","pages":"160-172"},"PeriodicalIF":2.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146018583","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}