{"title":"Effect of Verapamil on Blood Glucose in Type 1 and Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis.","authors":"Shiqi Tu, Ruiqi Zhang, Qiyue Zheng, Jiaojiao Wang, Yun Chen, Xiaosi Li, Jieyu He, Zhaokai Zhou, Qiong Lu","doi":"10.1007/s10557-025-07683-4","DOIUrl":"10.1007/s10557-025-07683-4","url":null,"abstract":"<p><strong>Purpose: </strong>Verapamil, an L-type calcium channel blocker treating hypertension, arrhythmia, and other cardiovascular diseases, has emerged as a potential drug for lowering blood glucose by regulating cellular calcium homeostasis and affecting expression of apoptosis-related proteins in pancreatic β-cells. However, this promising effect must be weighed against potential risks, including cardiovascular adverse effects of this drug.</p><p><strong>Methods: </strong>We conducted a systematic review and meta-analysis and included randomized controlled trials (RCTs) assessing verapamil in individuals with type 1 or type 2 diabetes. The primary outcomes were glycated hemoglobin (HbA1c) and serum glucose concentration. The secondary outcomes were area under the curve (AUC) values for C-peptide level, body weight, changes in HbA1c and blood glucose concentration pre- and post-intervention, and adverse drug reactions.</p><p><strong>Results: </strong>A total of eight RCTs involving 1100 patients were included in the analysis. Meta-analysis showed that verapamil effectively lowered blood glucose levels (weighted mean difference [WMD] -6.38, 95% CI -12.52, -0.25 mg/dL, P = 0.04; 6 trials), decreased HbA1c (WMD -0.45, 95% CI -0.66, -0.23%, P < 0.001; 7 trials), and increased C-peptide AUC (WMD 0.27, 95% CI 0.21, 0.32 pmol/mL, P < 0.0001; 2 trials) in patients with both type 1 and type 2 diabetes, without significant trial-related adverse events (OR 1.33, 95% CI 0.85, 2.09, P = 0.21).</p><p><strong>Conclusion: </strong>The adjunctive use of verapamil to standard hypoglycemic therapy is a safe and effective means of improving glycemic control in diabetic patients. However, the limited scale of RCTs and heterogeneity of basic glucose-lowering regimens across studies might constrain generalizability of these findings. Future high-quality research is warranted to further elucidate the role of verapamil in diabetes management.</p>","PeriodicalId":9557,"journal":{"name":"Cardiovascular Drugs and Therapy","volume":" ","pages":"347-359"},"PeriodicalIF":3.1,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143668921","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}
Ruikang Liu, Chiyun Sun, Jun Li, Guangyi Yang, Ke Xu, Jiaming Hu, Chao Meng, Xiao Xia, Yonghao Li, Yiying Liu
{"title":"Identifying Potential Drug Targets in Coronary Atherosclerosis: Insights from the Druggable Genome and Mendelian Randomization.","authors":"Ruikang Liu, Chiyun Sun, Jun Li, Guangyi Yang, Ke Xu, Jiaming Hu, Chao Meng, Xiao Xia, Yonghao Li, Yiying Liu","doi":"10.1007/s10557-025-07694-1","DOIUrl":"10.1007/s10557-025-07694-1","url":null,"abstract":"<p><strong>Purpose: </strong>This study aims to identify therapeutic targets for coronary atherosclerosis (CA) using publicly available datasets while exploring its pathophysiologic mechanisms, mediators and potential side effects.</p><p><strong>Methods: </strong>We conducted a two-sample Mendelian randomization (MR) and single-cell MR analyses integrating identified druggable genes to evaluate the causal relationship between expression quantitative trait loci (eQTL) and CA in both peripheral and central tissues. Using peripheral protein quantitative trait loci (pQTL) data, we further validated the identified targets at the proteomic level through summary data-based MR (SMR) and HEIDI tests. Concurrently, mediation MR analysis was employed to investigate potential mechanistic pathways underlying the role of these targets in CA. Additionally, a phenotype-wide MR (Phe-MR) analysis was performed to explore other potential indications for the therapeutic application of the identified targets.</p><p><strong>Results: </strong>In conclusion, we identified three CA-associated genes in peripheral tissues (VAMP8, MFGE8 and PDGFD) two CA-associated genes in central tissues (GGCX and NPEPPS). In addition, single-cell MR analyses revealed that GGCX was associated with increased CA risk in excitatory, inhibitory and oligodendrocyte precursor cells, whereas NPEPPS was associated with protection in oligodendrocyte lineage cells. Finally, Phe-MR analyses indicated possible indications and side effects of the targets.</p><p><strong>Conclusion: </strong>Our study provides genetic evidence for VAMP8, MFGE8, PDGFD, GGCX and NPEPPS as potential therapeutic targets for CA, highlighting their clinical relevance, associated risks and mediators, and providing valuable insights for the development of novel CA therapeutics.</p>","PeriodicalId":9557,"journal":{"name":"Cardiovascular Drugs and Therapy","volume":" ","pages":"155-166"},"PeriodicalIF":3.1,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143968094","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":"Transcutaneous Auricular Vagus Nerve Stimulation Ameliorates Heart Failure with Preserved Ejection Fraction Through Regulating Macrophage Polarization Mediated by Alpha7nAChR.","authors":"Jun-Yu Huo, Can Hou, Fang Jia, Cong Xue, Xiao-Long Li, Ling Yang, Wan-Ying Jiang, Xiaoying Zhang","doi":"10.1007/s10557-025-07695-0","DOIUrl":"10.1007/s10557-025-07695-0","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to investigate the effects of transcutaneous auricular vagus nerve stimulation (ta-VNS) on heart failure with preserved ejection fraction (HFpEF) and explore the related mechanisms.</p><p><strong>Methods: </strong>Sprague-Dawley rats were fed a high-fat diet and N<sup>[w]</sup>-nitro-L-arginine methyl ester to establish an HFpEF model. Ta-VNS was achieved by electrical stimulation of the auricular concha. Histology and echocardiography were used to identify changes in cardiac function and pathology. RNA sequencing was used to explore the underlying mechanism. RT‒PCR, WB, and immunofluorescence staining were used to determine the effects of ta-VNS on macrophage polarization. In vitro, RAW264.7 cells were induced into the M1 or M2 type. An α7nAChR agonist and an α7nAChR inhibitor were used to explore the effects of α7nAChR on macrophage polarization. Finally, an α7nAChR inhibitor was used to determine whether the therapeutic effects of ta-VNS are related to α7nAChR.</p><p><strong>Results: </strong>In vivo, ta-VNS alleviated cardiac dysfunction and pathological remodeling in rats with HFpEF. RNA sequencing demonstrated that the protective effects of ta-VNS on HFpEF were related to macrophage-mediated inflammatory responses. Ta-VNS decreased the expression of M1-type macrophage markers but increased the expression of M2-type markers. In vitro studies revealed that the α7nAChR agonist decreased the polarization of macrophages toward the M1 type, whereas the α7nAChR inhibitor reduced the polarization toward the M2 type. Furthermore, the α7nAChR inhibitor abolished the protective effects of ta-VNS on macrophage polarization and myocardial remodeling in rats with HFpEF.</p><p><strong>Conclusion: </strong>Ta-VNS ameliorated HFpEF-induced cardiac remodeling, which was associated with the modulation of macrophage polarization.</p>","PeriodicalId":9557,"journal":{"name":"Cardiovascular Drugs and Therapy","volume":" ","pages":"127-140"},"PeriodicalIF":3.1,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143794544","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":"Dissociation Between Mortality/Kidney Benefits and Neutral MACE Outcomes with ARNi in Heart Failure and Post-dialysis AKD Recovery.","authors":"Ahmed B Shamsulddin","doi":"10.1007/s10557-025-07715-z","DOIUrl":"10.1007/s10557-025-07715-z","url":null,"abstract":"","PeriodicalId":9557,"journal":{"name":"Cardiovascular Drugs and Therapy","volume":" ","pages":"17-18"},"PeriodicalIF":3.1,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143964992","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":"Downregulated TRIM35 Alleviates Doxorubicin-Induced Cardiotoxicity by Suppressing Oxidative Stress and Inflammation via Inhibiting TLR4/NF-κB Pathway.","authors":"Yewen Hu, Shiqi Wang, Chaoxia Zhang, Fuwei He, Yongxing Jiang, Ruoyu Chen, Jia Su, Caijie Shen, Xiaomin Chen, Huimin Chu","doi":"10.1007/s10557-025-07672-7","DOIUrl":"10.1007/s10557-025-07672-7","url":null,"abstract":"<p><strong>Purpose: </strong>The use of doxorubicin (DOX), a potent chemotherapy drug, is limited by its detrimental effects on the heart. This cardiotoxicity is primarily driven by oxidative stress and inflammation. TRIM35 plays a key role in inflammatory responses; however, its exact function in DOX-induced cardiotoxicity (DIC) remains to be fully understood. This study investigates the effects of TRIM35 on DIC and explores the underlying biological mechanisms.</p><p><strong>Methods: </strong>To assess the role of TRIM35, we reduced the expression of TRIM35 in the heart tissues of mice using an adeno-associated virus 9 (AAV9) system, delivered through tail vein injection. We then administered weekly doses of DOX (4 mg/kg) to C57BL/6 mice for 4 weeks to induce DIC. Echocardiography, histopathological assessments, and molecular techniques were employed to examine the effects and mechanisms of TRIM35 on DIC.</p><p><strong>Results: </strong>Our research found that DOX treatment increases TRIM35 levels in the heart. By lowering TRIM35 expression, we observed an improvement in cardiac function and a decrease in myocardial damage in DOX-treated mice. Additionally, reduced TRIM35 expression lessened myocardial hypertrophy and fibrosis. It also mitigated the oxidative stress and inflammation caused by DOX. Furthermore, the down-regulation of TRIM35 expression resulted in the downregulation of TLR4 and phosphorylated P65 expression.</p><p><strong>Conclusion: </strong>Downregulated TRIM35 expression mitigates the oxidative stress and inflammation caused by DOX, likely through impacting the TLR4/NF-κB signaling pathway. These insights indicate that TRIM35 holds promise as a therapeutic target for managing heart damage induced by DOX.</p>","PeriodicalId":9557,"journal":{"name":"Cardiovascular Drugs and Therapy","volume":" ","pages":"97-106"},"PeriodicalIF":3.1,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143425145","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}
Jianfan Zhen, Xiang Luo, Jie Liu, Zerui Chen, Jinlin Wu, Tucheng Sun
{"title":"Impact of Warfarin and Dual Antiplatelet Therapy on Graft Failure After Coronary Endarterectomy: A Retrospective Cohort Study.","authors":"Jianfan Zhen, Xiang Luo, Jie Liu, Zerui Chen, Jinlin Wu, Tucheng Sun","doi":"10.1007/s10557-024-07667-w","DOIUrl":"10.1007/s10557-024-07667-w","url":null,"abstract":"<p><strong>Purpose: </strong>Coronary endarterectomy combined with coronary artery bypass grafting (CE-CABG) effectively achieves coronary revascularization in patients with diffuse atherosclerotic coronary artery disease (CAD). However, the loss of the subendothelial tissue at the CE-CABG coronary artery accelerates local thrombosis, leading to CE-CABG graft failure. Dual antiplatelet therapy (DAT) and warfarin plus aspirin (WPA) are the two most common anticoagulation strategies post CE-CABG. This retrospective study compares the clinical outcomes and graft failure rates associated with these two approaches.</p><p><strong>Methods: </strong>This study is a retrospective cohort study. Between July 2016 and April 2024, 102 patients with diffuse CAD underwent CE-CABG. Six patients were excluded. In total, 96 patients (mean age 59.8 ± 7.7 years) enrolled in the study (43 in DAT group and 53 in WPA group). The DAT group received aspirin (100 mg, qd) and clopidogrel (75 mg, qd) for 1 year postoperatively, transitioning to aspirin (100 mg, qd) after 1 year. The WPA group received warfarin (international normalized ratio, INR remained at 1.8-2.5) and aspirin (100 mg, qd) for 3 months postoperatively, followed by DAT after 3 months, changed to aspirin monotherapy after 1 year. The primary endpoint was graft failure of the CE-CABG graft.</p><p><strong>Results: </strong>Four patients died during the perioperative period (1 in DAT group, 3 in WPA group), resulting in an overall perioperative mortality rate of 4.2%. Five patients were lost for follow-up. Mean follow-up time was 38 months. Three patients died during the follow-up period (1 in DAT group, 2 in WPA group). The CE-CABG graft patency of the WPA group was significantly higher compared to the DAT group (88.1% vs. 50.0%, P < 0.001). Kaplan-Meier analysis showed that the median graft failure time was significantly longer in the WPA group (77 months, 95% CI 69-85) compared to the DAT group (73 months, 95% CI 17-129, P = 0.017). A higher proportion of the DAT group was classified as NYHA III-IV compared to the WPA group (26.2% vs. 10.2%, P = 0.046). One patient of the WPA group had a gastrointestinal bleeding event, and the overall incidence of bleeding events was not statistically different between the two groups.</p><p><strong>Conclusion: </strong>Using the WPA strategy after CE-CABG significantly reduces the rate of graft failure and improves cardiac function without increasing the risk of bleeding events.</p>","PeriodicalId":9557,"journal":{"name":"Cardiovascular Drugs and Therapy","volume":" ","pages":"181-189"},"PeriodicalIF":3.1,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142977699","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}
Nur Liyana Mohammed Yusof, Derek M Yellon, Sean M Davidson
{"title":"Novel Selective Cardiac Myosin-Targeted Inhibitors Alleviate Myocardial Ischaemia-Reperfusion Injury.","authors":"Nur Liyana Mohammed Yusof, Derek M Yellon, Sean M Davidson","doi":"10.1007/s10557-024-07663-0","DOIUrl":"10.1007/s10557-024-07663-0","url":null,"abstract":"<p><strong>Purpose: </strong>Reperfusion of the ischaemic heart is essential to limit myocardial infarction. However, reperfusion can cause cardiomyocyte hypercontracture. Recently, cardiac myosin-targeted inhibitors (CMIs), such as Mavacamten (MYK-461) and Aficamten (CK-274), have been developed to treat patients with cardiac hypercontractility. These CMIs are well tolerated and safe in clinical trials. We hypothesised that, by limiting hypercontraction, CMIs may reduce hypercontracture and protect hearts in the setting of ischaemia and reperfusion (IR).</p><p><strong>Methods: </strong>We investigated the ability of MYK-461 and CK-274 to inhibit hypercontracture of adult rat cardiomyocytes (ARVC) in vitro following ATP depletion. A suitable dose of CMIs for subsequent in vivo IR studies was identified using cardiac echocardiography of healthy male Sprague Dawley rats. Rats were anaesthetized and subject to coronary artery ligation for 30 min followed by 2 h of reperfusion. Prior to reperfusion, CMI or vehicle was administered intraperitoneally. Ischaemic preconditioning (IPC) was used as a positive control group. Infarct size was assessed by tetrazolium chloride staining and extent of hypercontracture was assessed by histological staining.</p><p><strong>Results: </strong>Treatment with CMIs inhibited ARVC hypercontracture in vitro. MYK-461 (2 mg/kg) and CK-274 (0.5 mg/kg to 2 mg/kg) significantly reduced infarct size vs. vehicle. IR caused extensive contraction band necrosis, which was reduced significantly by IPC but not by CMIs, likely due to assay limitations. GDC-0326, an inhibitor of PI3Kα, abrogated CK-274-mediated protection following IR injury. GDC-0326 reduced phosphorylation of AKT when administered together with CK-274.</p><p><strong>Conclusion: </strong>This study identifies CMIs as novel cardioprotective agents in the setting of IR injury.</p>","PeriodicalId":9557,"journal":{"name":"Cardiovascular Drugs and Therapy","volume":" ","pages":"39-52"},"PeriodicalIF":3.1,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12872633/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142926757","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":"Association of Angiotensin Receptor-Neprilysin Inhibitors Use and Better Cardiorenal Outcomes in Patients With Heart Failure and Acute Kidney Disease.","authors":"Jui-Yi Chen, Heng-Chih Pan, Vin-Cent Wu","doi":"10.1007/s10557-025-07698-x","DOIUrl":"10.1007/s10557-025-07698-x","url":null,"abstract":"<p><strong>Purpose: </strong>Angiotensin receptor-neprilysin inhibitors (ARNi) have been shown to improve cardiovascular outcomes in heart failure (HF) patients. However, their impact on HF patients with concurrent acute kidney disease (AKD) remains underexplored. This study investigated the outcomes of ARNi compared to angiotensin-converting enzyme inhibitors (ACEi) in HF patients with AKD.</p><p><strong>Methods: </strong>The study included 20,009 hospitalized HF and AKD patients who underwent dialysis during hospitalization, recovered from dialysis within 90 days after discharge, and were followed until November 30, 2022, using data from TriNetX. The study period began in July 2015, coinciding with the availability of ARNi in the market. Propensity score matching (1:1) was applied to balance ARNi and ACEi groups. Adjusted hazard ratios (aHR) with 95% confidence intervals (CI) were calculated to assess the risks of mortality, major adverse kidney events (MAKE), readmission and major adverse cardiac events (MACE). The follow-up period was conducted with a maximum duration of 5 years.</p><p><strong>Results: </strong>A total of 20,009 AKD patients (mean [SD] age, 59.1 [12.2] years) were enrolled, of whom 21.9% received ARNi, with a median follow-up of 2.3 years. After matching, 4391 patients (mean age, 58.6 years; male, 67.9%) were identified in both the ARNi and control groups. ARNi users exhibited a significantly lower risk of mortality (aHR, 0.32, 95% CI 0.13-0.80, p = 0.01), MAKE (aHR, 0.58, 95% CI 0.51-0.66, p < 0.01 ), and readmission (aHR, 0.61, 95% CI 0.55-0.68, p <0.01) versus controls. However, no significant difference in the risk of MACE was observed between the two groups (aHR, 0.94, 95% CI 0.82-1.09, p = 0.78). Subgroup analysis revealed ARNi users, when concomitantly treated with mineralocorticoids, diuretics, or beta-blockers had significantly lower risks of mortality, readmission, and MAKE than the control group. In addition, ARNi significantly reduced mortality and MAKE in patients with GFR 30-60 mL/min/1.73 m<sup>2</sup>, irrespective of proteinuria status. However, no significant benefit was observed in patients with GFR <30 mL/min/1.73 m<sup>2</sup>.</p><p><strong>Conclusions: </strong>In HF patients with AKD, ARNi was associated with reduced all-cause mortality, MAKE, and readmission risks compared to ACEi, particularly with concurrent mineralocorticoids, diuretics, or beta-blockers. Future research is necessary to further investigate the impact of ARNi on outcomes in patients with HF and AKD.</p>","PeriodicalId":9557,"journal":{"name":"Cardiovascular Drugs and Therapy","volume":" ","pages":"251-262"},"PeriodicalIF":3.1,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12872734/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143983451","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":"Pocking the Ear for HFpEF?","authors":"Yochai Birnbaum, Seiji Takashima","doi":"10.1007/s10557-025-07712-2","DOIUrl":"10.1007/s10557-025-07712-2","url":null,"abstract":"","PeriodicalId":9557,"journal":{"name":"Cardiovascular Drugs and Therapy","volume":" ","pages":"11-13"},"PeriodicalIF":3.1,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143989997","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}
Junyan Zhang, Ting Yan, Ran Liu, Yuxiao Li, Minggang Zhou, Hua Wang, Chen Li, Li Rao, Zhongxiu Chen, Yong He
{"title":"Safety Analysis of Spironolactone Use in Patients Undergoing Percutaneous Coronary Intervention with High Bleeding Risk: A Propensity Score-Matched Study.","authors":"Junyan Zhang, Ting Yan, Ran Liu, Yuxiao Li, Minggang Zhou, Hua Wang, Chen Li, Li Rao, Zhongxiu Chen, Yong He","doi":"10.1007/s10557-025-07676-3","DOIUrl":"10.1007/s10557-025-07676-3","url":null,"abstract":"<p><strong>Purpose: </strong>Spironolactone has been reported to increase the risk of upper gastrointestinal bleeding in patients. We aimed to validate this perspective in a population of patients undergoing percutaneous coronary intervention with high bleeding risk (PCI-HBR).</p><p><strong>Methods: </strong>We prospectively included a total of 1616 PCI-HBR patients who were treated at West China Hospital of Sichuan University from May 2022 to July 2024. These patients were divided into a spironolactone treatment group (n = 301) and a non-spironolactone treatment group (n = 1315). A propensity score matching was performed at a 1:4 ratio, and Cox regression analysis was conducted on the matched data. Additionally, Kaplan-Meier curves were plotted to evaluate the direct correlation between spironolactone use and gastrointestinal bleeding. And the subgroup analysis is used to assess the robustness of the results.</p><p><strong>Results: </strong>In this study, after propensity score matching, a total of 927 patients were included in the outcome analysis, with 259 in the spironolactone group and 668 in the non-spironolactone group. Throughout the follow-up period, 14 (5.4%) and 42 (6.3%) patients experienced BARC 2-5 gastrointestinal bleeding events in the spironolactone and non-spironolactone groups, respectively, while 6 (2.3%) and 24 (3.6%) patients experienced BARC 3-5 gastrointestinal bleeding. The incidence of BARC 2-5 gastrointestinal bleeding was comparable between the groups (14/259 [5.4%] vs. 42/668 [6.3%]; HR 0.88 [0.48-1.62], p = 0.689), as was the incidence of BARC 3-5 gastrointestinal bleeding (6/259 [2.3%] vs. 24/668 [3.6%]; HR 0.69 [0.28-1.68], p = 0.410). No statistically significant interactions were found between spironolactone use and clinical variables such as acute coronary syndrome, diabetes, and chronic kidney disease concerning the risk of gastrointestinal bleeding.</p><p><strong>Conclusions: </strong>In summary, our prospective cohort study, which used propensity score matching, represents the first comprehensive investigation of spironolactone usage in PCI-HBR patients. Our results underscore that cardiologists need not routinely consider the risk of spironolactone-induced bleeding when making decisions about its use in patients. Larger randomized trials or analyses from existing randomized trials on spironolactone are warranted to draw definitive conclusions about the potential association between spironolactone and bleeding.</p>","PeriodicalId":9557,"journal":{"name":"Cardiovascular Drugs and Therapy","volume":" ","pages":"191-200"},"PeriodicalIF":3.1,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143188296","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}