CirculationPub Date : 2025-06-17Epub Date: 2025-06-16DOI: 10.1161/CIRCULATIONAHA.124.073533
Uwe Zeymer, Anne Freund, Marko Noc, Ibrahim Akin, Kurt Huber, Janine Pöss, Steffen Schneider, Tienush Rassaf, Christian Jung, Eike Tigges, Taoufik Ouarrak, Steffen Desch, Holger Thiele
{"title":"Influence of Resuscitated Cardiac Arrest on Efficacy and Safety of Extracorporeal Life Support in Infarct-Related Cardiogenic Shock: A Substudy of the ECLS-SHOCK Trial.","authors":"Uwe Zeymer, Anne Freund, Marko Noc, Ibrahim Akin, Kurt Huber, Janine Pöss, Steffen Schneider, Tienush Rassaf, Christian Jung, Eike Tigges, Taoufik Ouarrak, Steffen Desch, Holger Thiele","doi":"10.1161/CIRCULATIONAHA.124.073533","DOIUrl":"https://doi.org/10.1161/CIRCULATIONAHA.124.073533","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"151 24","pages":"1752-1754"},"PeriodicalIF":35.5,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144309599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
CirculationPub Date : 2025-06-17Epub Date: 2025-06-16DOI: 10.1161/CIRCULATIONAHA.125.074589
Davor Vukadinović, Lucas Lauder, Felix Mahfoud
{"title":"Response by Vukadinović et al to Letter Regarding Article, \"Effects of Catheter-Based Renal Denervation in Hypertension: A Systematic Review and Meta-Analysis\".","authors":"Davor Vukadinović, Lucas Lauder, Felix Mahfoud","doi":"10.1161/CIRCULATIONAHA.125.074589","DOIUrl":"https://doi.org/10.1161/CIRCULATIONAHA.125.074589","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"151 24","pages":"e1073-e1074"},"PeriodicalIF":35.5,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144309601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
CirculationPub Date : 2025-06-17DOI: 10.1161/CIRCULATIONAHA.125.074058
Steven A Muller, Babken Asatryan, Alessio Gasperetti, Maarten J Cramer, Ahmad S Amin, Peter Loh, Richard T Carrick, Moniek G P J Cox, Pim van der Harst, Marish I F J Oerlemans, Crystal Tichnell, Sing-Chien Yap, Brittney Murray, Stefan L Zimmerman, J Peter van Tintelen, Hugh Calkins, Anneline S J M Te Riele, Cynthia A James
{"title":"Family Screening in Relatives at Risk for Plakophilin-2-Associated Arrhythmogenic Right Ventricular Cardiomyopathy.","authors":"Steven A Muller, Babken Asatryan, Alessio Gasperetti, Maarten J Cramer, Ahmad S Amin, Peter Loh, Richard T Carrick, Moniek G P J Cox, Pim van der Harst, Marish I F J Oerlemans, Crystal Tichnell, Sing-Chien Yap, Brittney Murray, Stefan L Zimmerman, J Peter van Tintelen, Hugh Calkins, Anneline S J M Te Riele, Cynthia A James","doi":"10.1161/CIRCULATIONAHA.125.074058","DOIUrl":"https://doi.org/10.1161/CIRCULATIONAHA.125.074058","url":null,"abstract":"<p><strong>Background: </strong>Penetrance and risk of ventricular arrhythmias (VAs) in arrhythmogenic right ventricular cardiomyopathy (ARVC) are increasingly recognized as being genotype specific. Therefore, genotype-informed family screening protocols may lead to safer and more personalized recommendations than the current one-size-fits-all screening recommendations. We aimed to develop a safe, evidence-based plakophilin-2 (<i>PKP2</i>)-specific longitudinal screening algorithm.</p><p><strong>Methods: </strong>We included 295 relatives (41% male; age 30.9 years [18.0-47.7 years]) with a pathogenic or likely pathogenic <i>PKP2</i> variant from 145 families. Phenotype was ascertained with ECG, Holter monitoring, and cardiac imaging and classified by the 2010 Task Force Criteria. VA was defined as a composite of sudden cardiac arrest or death, spontaneous sustained ventricular tachycardia, ventricular fibrillation, or appropriate implantable cardioverter defibrillator intervention. We performed Cox regression to determine predictors of ARVC development and multistate modeling to assess the probability of ARVC development and occurrence of VA.</p><p><strong>Results: </strong>At baseline, 110 relatives (37%) had definite ARVC. During 8.5 years (4.2-12.9 years) of follow-up, 62 of 185 relatives (34%) without definite ARVC at baseline progressed to definite ARVC diagnosis, and 35 of 295 of all relatives (12%) had VA. VAs occurred only in relatives who previously fulfilled definite ARVC diagnosis. Relatives with borderline ARVC (fulfillment of one minor criterion plus the major family history criterion) progressed 5 times faster in the multistate model to definite ARVC diagnosis and compared with genotype-positive/phenotype-negative (G+/P-) relatives (ie, major family history criterion alone). Relatives 20 to 40 years of age had increased risk for developing definite ARVC (hazard ratio, 2.23; <i>P</i>=0.012) compared with those ≥40 years of age. New Task Force Criteria fulfillment most commonly occurred first on ECGs, followed by Holter monitoring and cardiac imaging. Consequently, 3 risk profiles were identified, and appropriate screening protocols were derived: relatives with borderline ARVC (annual ECG and Holter monitoring; complete evaluation [ie, ECGs, Holter monitoring, and imaging] every 2 years), younger (<40 years of age) or symptomatic G+/P- relatives (every 2 years an ECG and Holter monitoring; complete evaluation every 4 years), and older (≥40 years of age) and asymptomatic G+/P- relatives (complete evaluation every 5 years).</p><p><strong>Conclusions: </strong>An evidence-based longitudinal screening algorithm that integrates age, symptoms, and baseline clinical phenotype may improve patient care and improve efficiency of clinical resource allocation.</p>","PeriodicalId":10331,"journal":{"name":"Circulation","volume":" ","pages":""},"PeriodicalIF":35.5,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144309597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
CirculationPub Date : 2025-06-17Epub Date: 2025-06-16DOI: 10.1161/CIRCULATIONAHA.124.073607
Fan Zhang, Yifei Zhong
{"title":"Letter by Zhang and Zhong Regarding Article, \"Effects of Catheter-Based Renal Denervation in Hypertension: A Systematic Review and Meta-Analysis\".","authors":"Fan Zhang, Yifei Zhong","doi":"10.1161/CIRCULATIONAHA.124.073607","DOIUrl":"https://doi.org/10.1161/CIRCULATIONAHA.124.073607","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"151 24","pages":"e1072"},"PeriodicalIF":35.5,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144309600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
CirculationPub Date : 2025-06-17Epub Date: 2025-06-16DOI: 10.1161/CIRCULATIONAHA.125.074167
Rima Arnaout
{"title":"From Bytes to Beats: Overcoming Conceptual and Implementation Challenges for AI in Cardiovascular Care.","authors":"Rima Arnaout","doi":"10.1161/CIRCULATIONAHA.125.074167","DOIUrl":"10.1161/CIRCULATIONAHA.125.074167","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"151 24","pages":"1697-1698"},"PeriodicalIF":35.5,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12173426/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144309598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Inactivation of RhoA for Hypertension Treatment Through the TRPV4-RhoA-RhoGDI1 Axis.","authors":"Jiawen Wang,Zhen Yuan,Na Yu,Qian Jiao,Honglei Zhou,Wenjie Liao,Jiwei Shan,Shanshan Ruan,Yi Zhao,Ya Mo,Luyao Qi,Tiejun Li,Jianjun Fu,Bowen Ke,Yufang Xu,Xuhong Qian,Jian Zhang,Zhenjiang Zhao,Shiliang Li,Rui Wang,Honglin Li","doi":"10.1161/circulationaha.124.071884","DOIUrl":"https://doi.org/10.1161/circulationaha.124.071884","url":null,"abstract":"BACKGROUNDThe RhoA (Ras homolog family member A) signaling pathway is pivotal in regulating vascular smooth muscle cells (VSMCs) function and blood pressure homeostasis. Current inhibitors of the RhoA signaling pathway are limited in hypertension treatment, suffering from poor efficacy, insufficient specificity, and developmental challenges.METHODSCryo-electron microscopy (EM), proximity ligation assay (PLA), and site-directed mutagenesis were used to explore the mechanism of RhoA activity regulation. VSMC, hypertensive animal models, Trpv4-/- and Arhgdiaf/f Myh11-CREERT2 (smooth muscle-specific RhoGDI1 knockout) mice were used to investigate the role of the TRPV4 (transient receptor potential cation channel subfamily V member 4)-RhoA-RhoGDI1 (Rho GDP dissociation inhibitor 1) axis in hypertension.RESULTSAH001 ((R)-1-(3-ethylphenyl) ethane-1,2-diol) was identified as a novel inhibitor of the RhoA signaling pathway. It targets the TRPV4-RhoA-RhoGDI1 axis to effectively sequester inactive RhoA-GDP in the plasma membrane and cytoplasm, which is distinct from typical RhoA inhibition modes. The cryo-EM structure of the TRPV4AH001-RhoA complex showed that AH001-bound TRPV4 adopts a closed state with RhoA in an inactive GDP-bound state. Functional studies further revealed that AH001 reduced the pool of active RhoA by enhancing TRPV4-RhoA binding and facilitating RhoGDI1-RhoA interaction in VSMC. This inhibition notably decreased both acute and long-term blood pressure and prevented vascular remodeling in Ang II-induced hypertensive mice and spontaneously hypertensive rats. However, these antihypertensive effects were weakened in Trpv4-/- and Arhgdiaf/f Myh11-CREERT2 mice. Additionally, AH001 effectively inhibited VSMC contraction via the RhoA/ROCK (Rho-associated protein kinase)/MYPT1 (myosin phosphatase target subunit 1)/MLC (myosin light chain 2) signaling pathway and suppressed VSMC phenotype switching to myofibroblasts through the RhoA/ROCK/LIMK1 (LIM domain kinase)/cofilin/MRTF-A (myocardin-related transcription factor A)/SRF (serum response factor) signaling cascade. TRPV4 and RhoGDI1 knockdown attenuated AH001's inhibition of VSMC contraction and phenotypic switching to myofibroblasts.CONCLUSIONSThis study revealed a novel mode of RhoA signaling inhibition targeting the TRPV4-RhoA-RhoGDI1 axis, offering new insights for future antihypertensive drug development and proposing innovative strategies for targeting challenging Rho GTPases.","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"605 1","pages":""},"PeriodicalIF":37.8,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144295661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
CirculationPub Date : 2025-06-13DOI: 10.1161/CIRCULATIONAHA.125.075254
Massimiliano Greco, Gaetano Lombardi, Claudia Brusasco, Marina Pieri, Agostino Roasio, Fabrizio Monaco, Levan Berikashvili, Alessandro Belletti, Francesco Meroi, Stefano Fresilli, Aituar Kabibulatov, Giuseppe Giardina, Andrea Russo, Federico Mattia Oliva, Sergey Efremov, Rosalba Lembo, Lini Wang, Simone Vietri, Elena Momesso, Filippo D'Amico, Kristina Kadantseva, Rosa Labanca, Pavel Ryzhkov, Marilena Marmiere, Valery Subbotin, Alessandro Pruna, Nerlep Rana, Francesca Livi, Hugo Mantilla-Gutierrez, Fabio Guarracino, Lorenzo Schiavoni, Ivan Šitum, Marco Micali, Stefano Bosso, Anastasia Smirnova, Giuseppe Fresta, Andrey Cherednichenko, Luigi Beretta, Giacomo Monti, Lian Kah Ti, Pasquale Sansone, Francesco Corradi, Maurizio Cecconi, Andrey Yavorovskiy, Chong Lei, Aidos Konkayev, Tiziana Bove, Valery Likhvantsev, Alberto Zangrillo, Giovanni Landoni, Rinaldo Bellomo, Remo Daniel Covello, Stefano Turi
{"title":"Effect of Remote Ischemic Preconditioning on Myocardial Injury in Noncardiac Surgery: the PRINCE Randomized Clinical Trial.","authors":"Massimiliano Greco, Gaetano Lombardi, Claudia Brusasco, Marina Pieri, Agostino Roasio, Fabrizio Monaco, Levan Berikashvili, Alessandro Belletti, Francesco Meroi, Stefano Fresilli, Aituar Kabibulatov, Giuseppe Giardina, Andrea Russo, Federico Mattia Oliva, Sergey Efremov, Rosalba Lembo, Lini Wang, Simone Vietri, Elena Momesso, Filippo D'Amico, Kristina Kadantseva, Rosa Labanca, Pavel Ryzhkov, Marilena Marmiere, Valery Subbotin, Alessandro Pruna, Nerlep Rana, Francesca Livi, Hugo Mantilla-Gutierrez, Fabio Guarracino, Lorenzo Schiavoni, Ivan Šitum, Marco Micali, Stefano Bosso, Anastasia Smirnova, Giuseppe Fresta, Andrey Cherednichenko, Luigi Beretta, Giacomo Monti, Lian Kah Ti, Pasquale Sansone, Francesco Corradi, Maurizio Cecconi, Andrey Yavorovskiy, Chong Lei, Aidos Konkayev, Tiziana Bove, Valery Likhvantsev, Alberto Zangrillo, Giovanni Landoni, Rinaldo Bellomo, Remo Daniel Covello, Stefano Turi","doi":"10.1161/CIRCULATIONAHA.125.075254","DOIUrl":"https://doi.org/10.1161/CIRCULATIONAHA.125.075254","url":null,"abstract":"<p><strong>Background: </strong>Major noncardiac surgery carries high rates of postoperative myocardial injury and other complications. Remote ischemic preconditioning (RIPC) was reported to decrease these complications. However, such supportive evidence lacks robustness.</p><p><strong>Methods: </strong>In a multinational, double-blind trial, we randomly assigned adult high-risk patients undergoing noncardiac surgical procedures to receive RIPC or sham-RIPC after the induction of general anesthesia and before surgery. RIPC involved three 5-minute ischemic cycles, each followed by 5 minutes of reperfusion, using a blood-pressure cuff inflated to 200 mmHg. The primary endpoint was the rate of myocardial injury defined by an increase in postoperative troponin levels above the highest 99th percentile of reference values. Secondary outcomes included myocardial infarction, stroke, acute kidney injury, need for intensive care unit, length of hospital stay and 30-day all-cause mortality.</p><p><strong>Results: </strong>We recruited 1213 patients in 25 hospitals and 8 countries. We randomly assigned 599 to RIPC and 614 to sham-RIPC. The most frequent surgical procedures were abdominal and intrathoracic surgeries (406 patients, 33.6%). RIPC was applied to the upper limb in 1,014 patients (84.8%) and to the lower limb in 182 patients (15.2%). Postoperative myocardial injury occurred in 215/566 patients (38.0%) in the RIPC group and in 223/596 patients (37.4%) in the sham-RIPC group (relative risk, 1.02; 95% confidence interval, 0.88 to 1.18; <i>P</i>=0.84). There were no significant differences in the rate of any secondary outcomes. We observed eleven episodes of limb petechiae (10 [1.7%] in the RIPC group vs 1 [0.2%] in the sham-RIPC group) and 34 (6.0%) hospital readmissions in the RIPC group vs 20 (3.5%) in the sham-RIPC group.</p><p><strong>Conclusions: </strong>Among adult patients undergoing noncardiac surgery, RIPC did not reduce myocardial injury or other postoperative complications.</p>","PeriodicalId":10331,"journal":{"name":"Circulation","volume":" ","pages":""},"PeriodicalIF":35.5,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144282640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
CirculationPub Date : 2025-06-12DOI: 10.1161/CIR.0000000000001342
Lisa Q Rong, Linda Shore-Lesserson, Kiran Belani, Abimbola Faloye, Enrique Garcia-Sayan, Jennifer Lawton, Timothy Maus, Wanda Miller-Hance, Alina Nicoara, Richard Sheu
{"title":"Considerations of Intraoperative Transesophageal Echocardiography During Adult Cardiac Surgery: A Scientific Statement From the American Heart Association.","authors":"Lisa Q Rong, Linda Shore-Lesserson, Kiran Belani, Abimbola Faloye, Enrique Garcia-Sayan, Jennifer Lawton, Timothy Maus, Wanda Miller-Hance, Alina Nicoara, Richard Sheu","doi":"10.1161/CIR.0000000000001342","DOIUrl":"https://doi.org/10.1161/CIR.0000000000001342","url":null,"abstract":"<p><p>Intraoperative transesophageal echocardiography is used with increasing frequency in cardiac surgery for monitoring and diagnostic purposes. Recent data have shown the impact of improved outcomes in patients undergoing cardiac surgery and the use of intraoperative transesophageal echocardiography in managing complex surgical decisions. However, specialty society recommendations have not been updated to reflect these trends. This scientific statement reviews the state-of-the-art practice of intraoperative echocardiography, summarizes the association of the use of intraoperative transesophageal echocardiography with enhanced outcomes, and provides specific perioperative and procedural transesophageal echocardiography considerations in the cardiac surgical population.</p>","PeriodicalId":10331,"journal":{"name":"Circulation","volume":" ","pages":""},"PeriodicalIF":35.5,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144274300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
CirculationPub Date : 2025-06-10Epub Date: 2025-03-29DOI: 10.1161/CIRCULATIONAHA.125.074545
Nikolaus Marx, John E Deanfield, Johannes F E Mann, Rosario Arechavaleta, Stephen C Bain, Harpreet S Bajaj, Katrine Bayer Tanggaard, Andreas L Birkenfeld, John B Buse, Zaklina Davicevic-Elez, Cyrus Desouza, Scott S Emerson, Mads D M Engelmann, G Kees Hovingh, Silvio E Inzucchi, Pardeep S Jhund, Sharon L Mulvagh, Rodica Pop-Busui, Neil R Poulter, Søren Rasmussen, Shih-Te Tu, Darren K McGuire
{"title":"Oral Semaglutide and Cardiovascular Outcomes in People With Type 2 Diabetes, According to SGLT2i Use: Prespecified Analyses of the SOUL Randomized Trial.","authors":"Nikolaus Marx, John E Deanfield, Johannes F E Mann, Rosario Arechavaleta, Stephen C Bain, Harpreet S Bajaj, Katrine Bayer Tanggaard, Andreas L Birkenfeld, John B Buse, Zaklina Davicevic-Elez, Cyrus Desouza, Scott S Emerson, Mads D M Engelmann, G Kees Hovingh, Silvio E Inzucchi, Pardeep S Jhund, Sharon L Mulvagh, Rodica Pop-Busui, Neil R Poulter, Søren Rasmussen, Shih-Te Tu, Darren K McGuire","doi":"10.1161/CIRCULATIONAHA.125.074545","DOIUrl":"10.1161/CIRCULATIONAHA.125.074545","url":null,"abstract":"<p><strong>Background: </strong>Both GLP-1 (glucagon-like peptide-1) receptor agonists and SGLT2 (sodium-glucose cotransporter-2) inhibitors (SGLT2i) improve cardiovascular outcomes in people with type 2 diabetes and cardiovascular or chronic kidney disease. However, there are limited data about the effect of combining these agents on cardiovascular and safety outcomes.</p><p><strong>Methods: </strong>The SOUL trial (Semaglutide Cardiovascular Outcomes Trial; NCT03914326) randomized 9650 participants with type 2 diabetes and atherosclerotic cardiovascular disease and/or chronic kidney disease to oral semaglutide or placebo. As prespecified, participants were analyzed according to baseline use of SGLT2i (yes, n=2596; no, n=7054), and subsequently for any use of SGLT2i during the trial (yes, n=4718; no, n=4932). The primary outcome was time to first major adverse cardiovascular event, defined as cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. Safety was evaluated by comparing the incidence of serious adverse events.</p><p><strong>Results: </strong>Over a mean follow-up of 47.5±10.9 months, the risk of the primary outcome in the overall trial population was 14% lower for oral semaglutide versus placebo (hazard ratio, 0.86; 95% CI, 0.77-0.96). In those taking SGLT2i at baseline, there were 143 of 1296 (semaglutide) versus 158 of 1300 (placebo) primary outcome events (hazard ratio, 0.89; 95% CI, 0.71-1.11); and 436 of 3529 versus 510 of 3525, respectively, in participants not taking SGLT2i at baseline (hazard ratio, 0.84; 95% CI, 0.74-0.95; <i>P</i>-interaction, 0.66). An analysis of major adverse cardiovascular events by any in-trial SGLT2i use versus no use also showed no evidence of heterogeneity in the effects of oral semaglutide. The adverse event profiles of oral semaglutide with or without concomitant SGLT2i were similar.</p><p><strong>Conclusions: </strong>Oral semaglutide reduced major adverse cardiovascular event outcomes independently of concomitant SGLT2i treatment, and this combination appeared to be safe.</p><p><strong>Registration: </strong>URL: https://www.clinicaltrials.gov; Unique identifier: NCT03914326.</p>","PeriodicalId":10331,"journal":{"name":"Circulation","volume":" ","pages":"1639-1650"},"PeriodicalIF":35.5,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12144549/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}