Pub Date : 2024-11-01DOI: 10.1097/FJC.0000000000001616
Ning Gu, Panke Chen, Xi Wang, Changyin Shen, Yi Deng, Jianling Chen, Yi Ma, Shuai Ma, Xingwei Hu, Ranzun Zhao, Bei Shi
Abstract: The aim of this study was to explore the relationship between in-stent neoatherosclerosis (ISNA) and the neutrophil-to-lymphocyte ratio (NLR) in patients with in-stent restenosis (ISR) following drug-eluting stent (DES) implantation. We divided 216 patients into 3 groups based on the NLR tertile. We performed a comparative analysis of baseline, angiographic, and features of optical coherence tomography (OCT) between the NLR groups and performed univariate and multivariate logistic regression analyses to assess the association of the NLR with ISNA and in-stent thin-cap fibroatheroma (TCFA). Patients in the third tertile NLR group had a higher incidence of ISNA and in-stent TCFA compared with those in the first tertile. Multivariate logistic regression analysis showed that the hazard ratios and 95% confidence intervals for ISNA and TCFA were 2.673 (1.257-5.684; P = 0.038) and 4.272 (1.740-10.488; P = 0.004), respectively, for patients in the highest tertile compared with those in the lowest tertile. Our study showed that an increased NLR was associated with ISNA and in-stent plaque fragility in patients with ISR following DES implantation.
{"title":"Association Between the Neutrophil-to-Lymphocyte Ratio and in-Stent Neoatherosclerosis and Plaque Vulnerability: An Optical Coherence Tomography Study.","authors":"Ning Gu, Panke Chen, Xi Wang, Changyin Shen, Yi Deng, Jianling Chen, Yi Ma, Shuai Ma, Xingwei Hu, Ranzun Zhao, Bei Shi","doi":"10.1097/FJC.0000000000001616","DOIUrl":"10.1097/FJC.0000000000001616","url":null,"abstract":"<p><strong>Abstract: </strong>The aim of this study was to explore the relationship between in-stent neoatherosclerosis (ISNA) and the neutrophil-to-lymphocyte ratio (NLR) in patients with in-stent restenosis (ISR) following drug-eluting stent (DES) implantation. We divided 216 patients into 3 groups based on the NLR tertile. We performed a comparative analysis of baseline, angiographic, and features of optical coherence tomography (OCT) between the NLR groups and performed univariate and multivariate logistic regression analyses to assess the association of the NLR with ISNA and in-stent thin-cap fibroatheroma (TCFA). Patients in the third tertile NLR group had a higher incidence of ISNA and in-stent TCFA compared with those in the first tertile. Multivariate logistic regression analysis showed that the hazard ratios and 95% confidence intervals for ISNA and TCFA were 2.673 (1.257-5.684; P = 0.038) and 4.272 (1.740-10.488; P = 0.004), respectively, for patients in the highest tertile compared with those in the lowest tertile. Our study showed that an increased NLR was associated with ISNA and in-stent plaque fragility in patients with ISR following DES implantation.</p>","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":"84 5","pages":"506-514"},"PeriodicalIF":2.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11537471/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602070","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":"Commentary on Antithrombotic Effect of Protopanaxatriol Saponins from Panax notoginseng Using Zebrafish Model.","authors":"Alfredo Caturano, Vincenzo Russo, Marcellino Monda, Celestino Sardu, Raffaele Marfella, Ferdinando Carlo Sasso","doi":"10.1097/FJC.0000000000001621","DOIUrl":"10.1097/FJC.0000000000001621","url":null,"abstract":"","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":" ","pages":"493-495"},"PeriodicalIF":2.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141901864","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}
Abstract: Panax notoginseng has the effect of stimulating circulation to end stasis. Our study was designed to evaluate the anti-thrombotic effect of protoparaxotriol saponins (PTS) from P. notoginseng and the involved mechanisms. A thrombosis model was constructed, and the anti-thrombotic activity of PTS was determined by erythrocyte staining, heart rate, and blood flow velocity. In addition, quantitative real-time polymerase chain reaction was used to identify changes in the expression of genes related to coagulation, inflammation, and apoptosis. PTS alleviated arachidonic acid-induced caudal vein thrombosis, restored blood flow, and increased the area of cardiac erythrocyte staining, heart rate, and blood flow velocity. It reduced the ponatinib-induced cerebral thrombus area and decreased the intensity of erythrocyte staining. The quantitative polymerase chain reaction data showed that the anti-thrombotic effect of PTS was mediated by suppression of genes related to coagulation, inflammation, and apoptosis and also involved inhibition of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathways.
{"title":"Anti-Thrombotic Effect of Protoparaxotriol Saponins From Panax notoginseng Using Zebrafish Model.","authors":"Xin Liu, Wei Fan, Shenghua Lin, Jiayu Chen, Shanshan Zhang, Xiaobin Li, Meng Jin, Qiuxia He","doi":"10.1097/FJC.0000000000001604","DOIUrl":"10.1097/FJC.0000000000001604","url":null,"abstract":"<p><strong>Abstract: </strong>Panax notoginseng has the effect of stimulating circulation to end stasis. Our study was designed to evaluate the anti-thrombotic effect of protoparaxotriol saponins (PTS) from P. notoginseng and the involved mechanisms. A thrombosis model was constructed, and the anti-thrombotic activity of PTS was determined by erythrocyte staining, heart rate, and blood flow velocity. In addition, quantitative real-time polymerase chain reaction was used to identify changes in the expression of genes related to coagulation, inflammation, and apoptosis. PTS alleviated arachidonic acid-induced caudal vein thrombosis, restored blood flow, and increased the area of cardiac erythrocyte staining, heart rate, and blood flow velocity. It reduced the ponatinib-induced cerebral thrombus area and decreased the intensity of erythrocyte staining. The quantitative polymerase chain reaction data showed that the anti-thrombotic effect of PTS was mediated by suppression of genes related to coagulation, inflammation, and apoptosis and also involved inhibition of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathways.</p>","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":" ","pages":"528-538"},"PeriodicalIF":2.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141723713","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}
Abstract: Heart failure has always been a prevalent, disabling, and potentially life-threatening disease. For the treatment of heart failure, controlling cardiac remodeling is very important. In recent years, clinical trials have shown that sodium-glucose cotransporter-2 (SGLT-2) inhibitors not only excel in lowering glucose levels but also demonstrate favorable cardiovascular protective effects. However, the precise mechanisms behind the cardiovascular benefits of SGLT-2 inhibitors remain elusive. In this research, we assessed the impact of canagliflozin (CANA, an SGLT-2 inhibitor) on cardiac remodeling progression in mice and preliminarily elucidated the possible mechanism of action of the SGLT-2 inhibitor. Our results indicate that the administration of canagliflozin significantly attenuates myocardial hypertrophy and fibrosis and enhances cardiac ejection function in mice with isoprenaline (ISO)-induced cardiac remodeling. Notably, excessive mitophagy, along with mitochondrial structural abnormalities observed in ISO-induced cardiac remodeling, was mitigated by canagliflozin treatment, thereby attenuating cardiac remodeling progression. Furthermore, the differential expression of AMPK/PINK1/Parkin pathway-related proteins in ISO-induced cardiac remodeling was effectively reversed by canagliflozin, suggesting the therapeutic potential of targeting this pathway with the drug. Thus, our study indicates that canagliflozin holds promise in mitigating cardiac injury, enhancing cardiac function, and potentially exerting cardioprotective effects by modulating mitochondrial function and mitophagy through the AMPK/PINK1/Parkin pathway.
心力衰竭一直是一种常见病、致残性疾病,而且可能危及生命。对于心力衰竭的治疗,控制心脏重塑非常重要。近年来,临床试验表明,SGLT-2 抑制剂不仅能有效降低血糖水平,还能起到保护心血管的作用。然而,SGLT-2 抑制剂对心血管有益的确切机制仍不清楚。在目前的研究中,我们评估了卡格列净(CANA,一种 SGLT-2 抑制剂)对小鼠心脏重塑进展的影响,并初步阐明了 SGLT-2 抑制剂的可能作用机制。我们的研究结果表明,服用卡格列净可明显减轻异丙肾上腺素(ISO)诱导的小鼠心肌肥厚和纤维化,并增强心脏射血功能。值得注意的是,在 ISO 诱导的心脏重构中观察到的过度有丝分裂和线粒体结构异常在卡格列净治疗后得到缓解,从而减轻了心脏重构的进展。此外,在 ISO 诱导的心脏重构中,AMPK/PINK1/Parkin 通路相关蛋白的差异表达也被 canagliflozin 有效逆转,这表明以该通路为靶点的药物具有治疗潜力。因此,我们的研究表明,卡格列净有望通过AMPK/PINK1/Parkin通路调节线粒体功能和有丝分裂,从而减轻心脏损伤、增强心脏功能并发挥潜在的心脏保护作用。
{"title":"Canagliflozin Mediates Mitophagy Through the AMPK/PINK1/Parkin Pathway to Alleviate ISO-induced Cardiac Remodeling.","authors":"Shaolin Gong, Yuan Sui, Mengxuan Xiao, Daoyao Fu, Zhiping Xiong, Liuping Zhang, Qingshan Tian, Yongnan Fu, Wenjun Xiong","doi":"10.1097/FJC.0000000000001625","DOIUrl":"10.1097/FJC.0000000000001625","url":null,"abstract":"<p><strong>Abstract: </strong>Heart failure has always been a prevalent, disabling, and potentially life-threatening disease. For the treatment of heart failure, controlling cardiac remodeling is very important. In recent years, clinical trials have shown that sodium-glucose cotransporter-2 (SGLT-2) inhibitors not only excel in lowering glucose levels but also demonstrate favorable cardiovascular protective effects. However, the precise mechanisms behind the cardiovascular benefits of SGLT-2 inhibitors remain elusive. In this research, we assessed the impact of canagliflozin (CANA, an SGLT-2 inhibitor) on cardiac remodeling progression in mice and preliminarily elucidated the possible mechanism of action of the SGLT-2 inhibitor. Our results indicate that the administration of canagliflozin significantly attenuates myocardial hypertrophy and fibrosis and enhances cardiac ejection function in mice with isoprenaline (ISO)-induced cardiac remodeling. Notably, excessive mitophagy, along with mitochondrial structural abnormalities observed in ISO-induced cardiac remodeling, was mitigated by canagliflozin treatment, thereby attenuating cardiac remodeling progression. Furthermore, the differential expression of AMPK/PINK1/Parkin pathway-related proteins in ISO-induced cardiac remodeling was effectively reversed by canagliflozin, suggesting the therapeutic potential of targeting this pathway with the drug. Thus, our study indicates that canagliflozin holds promise in mitigating cardiac injury, enhancing cardiac function, and potentially exerting cardioprotective effects by modulating mitochondrial function and mitophagy through the AMPK/PINK1/Parkin pathway.</p>","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":" ","pages":"496-505"},"PeriodicalIF":2.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141988074","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}
Pub Date : 2024-11-01DOI: 10.1097/FJC.0000000000001626
Jinlong Shi, Bingfeng Guan, Minghui Gong, Xinyi He
Abstract: Ischemic heart disease gravely threatens human health and even results in death. Kirenol is predominantly derived from the Herba Siegesbeckiae plant species and possesses a wide range of biological effects (such as antibacterial, anti-inflammatory, anticancer, and cardioprotective). However, the regulatory effects and associated mechanisms of kirenol in myocardial ischemia/reperfusion injury (MI/RI) remain unclear. In this study, first, the MI/RI rat model was established. It was demonstrated that kirenol protected against the aggravation of cardiac function in MI/RI rats. In addition, the inflammation was induced by ischemia reperfusion (IR), which was likewise affected by kirenol (5 or 10 mg/kg). Moreover, IR enhanced oxidative stress, a process that was counteracted by kirenol. Next, cell apoptosis was discovered to be heightened after IR, but this effect was neutralized by kirenol. Finally, it was revealed that kirenol has the ability to block the activation of the NF-κB pathway. In conclusion, it was disclosed that kirenol alleviated inflammation and oxidative stress through modulating the NF-κB pathway to improve MI/RI in rats. This work may offer novel insights for searching useful drugs for treating MI/RI.
{"title":"Kirenol Alleviates Inflammation and Oxidative Stress to Improve Myocardial Ischemia/Reperfusion Injury in Rats.","authors":"Jinlong Shi, Bingfeng Guan, Minghui Gong, Xinyi He","doi":"10.1097/FJC.0000000000001626","DOIUrl":"10.1097/FJC.0000000000001626","url":null,"abstract":"<p><strong>Abstract: </strong>Ischemic heart disease gravely threatens human health and even results in death. Kirenol is predominantly derived from the Herba Siegesbeckiae plant species and possesses a wide range of biological effects (such as antibacterial, anti-inflammatory, anticancer, and cardioprotective). However, the regulatory effects and associated mechanisms of kirenol in myocardial ischemia/reperfusion injury (MI/RI) remain unclear. In this study, first, the MI/RI rat model was established. It was demonstrated that kirenol protected against the aggravation of cardiac function in MI/RI rats. In addition, the inflammation was induced by ischemia reperfusion (IR), which was likewise affected by kirenol (5 or 10 mg/kg). Moreover, IR enhanced oxidative stress, a process that was counteracted by kirenol. Next, cell apoptosis was discovered to be heightened after IR, but this effect was neutralized by kirenol. Finally, it was revealed that kirenol has the ability to block the activation of the NF-κB pathway. In conclusion, it was disclosed that kirenol alleviated inflammation and oxidative stress through modulating the NF-κB pathway to improve MI/RI in rats. This work may offer novel insights for searching useful drugs for treating MI/RI.</p>","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":" ","pages":"539-544"},"PeriodicalIF":2.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142072935","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}
Pub Date : 2024-11-01DOI: 10.1097/FJC.0000000000001624
Wei-Syun Hu, Cheng-Li Lin
Abstract: The aim of this study was to explore the incidence of new-onset erectile dysfunction (ED) in diabetes mellitus (DM) patients with sodium-glucose cotransporter 2 inhibitors (SGLT2I) use compared with a control group of non-SGLT2I use by propensity score matching approach. Cox proportional hazards regression models were used to examine the effect of SGLT2I and risk factors on the risk of developing ED, presented as a hazard ratio with a 95% confidence interval. One lakhs fifty nine thousand seven hundred seventy three patients with DM using SGLT2I and 159,773 propensity score matching patients with DM who had never used SGLT2I were included. SGLT2I users had a higher risk of ED than the non-SGLT2I users (adjusted hazard ratio = 1.55, 95% confidence interval = 1.40-1.72). The likelihood of developing ED was higher in patients with SGLT2I use was found.
{"title":"Erectile Dysfunction Risk Among Patients With Diabetes Mellitus Using Sodium-Glucose Cotransporter 2 Inhibitors.","authors":"Wei-Syun Hu, Cheng-Li Lin","doi":"10.1097/FJC.0000000000001624","DOIUrl":"10.1097/FJC.0000000000001624","url":null,"abstract":"<p><strong>Abstract: </strong>The aim of this study was to explore the incidence of new-onset erectile dysfunction (ED) in diabetes mellitus (DM) patients with sodium-glucose cotransporter 2 inhibitors (SGLT2I) use compared with a control group of non-SGLT2I use by propensity score matching approach. Cox proportional hazards regression models were used to examine the effect of SGLT2I and risk factors on the risk of developing ED, presented as a hazard ratio with a 95% confidence interval. One lakhs fifty nine thousand seven hundred seventy three patients with DM using SGLT2I and 159,773 propensity score matching patients with DM who had never used SGLT2I were included. SGLT2I users had a higher risk of ED than the non-SGLT2I users (adjusted hazard ratio = 1.55, 95% confidence interval = 1.40-1.72). The likelihood of developing ED was higher in patients with SGLT2I use was found.</p>","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":" ","pages":"545-549"},"PeriodicalIF":2.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142072934","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}
Pub Date : 2024-11-01DOI: 10.1097/FJC.0000000000001620
Benjamin D Henson, Claudia A Bale-Neary, Ryan Mecaskey, Ogechi Gbujie, Michelle Zhan, Krishnasree Rao, Salvatore Carbone
Abstract: Patients undergoing anthracycline-based cancer treatments have an increased risk of heart failure or worsening preexisting heart failure as well as adverse metabolic outcomes such as malnutrition and cachexia. This retrospective study explored the impact of sodium-glucose cotransporter 2 inhibitors (SGLT2i) on these outcomes in patients with heart failure previously treated with anthracyclines. Using the TriNetX research network, we identified 1545 patients with a history of SGLT2i use and 17,681 patients without a history of SGLT2i use. We then performed 1:1 propensity score matching resulting in 1323 patients within each cohort. Patients were analyzed over a 5-year period. SGLT2i use was associated with significantly reduced risks of cachexia {hazard ratio (HR) 0.453, 95% confidence interval (CI) [0.286-0.718]}, malnutrition (HR 0.702, 95% CI [0.547-0.900]), adult failure to thrive (HR 0.489, 95% CI [0.345-0.693]), and all-cause mortality (HR 0.490, 95% CI [0.423-0.568]). These findings call for additional research to determine whether SGLT2i may indeed improve nutritional status and survival in patients with heart failure receiving anthracycline therapy.
接受蒽环类癌症治疗的患者发生心力衰竭(HF)和不良代谢结果(如营养不良和恶病质)的风险会增加。这项回顾性研究探讨了钠-葡萄糖协同转运体 2 抑制剂(SGLT2i)对既往接受过蒽环类药物治疗的心力衰竭患者上述结果的影响。通过 TriNetx 研究网络,我们确定了 1,545 名有 SGLT2i 使用史的患者和 17,681 名无 SGLT2i 使用史的患者。然后,我们进行了 1:1 倾向评分匹配,结果每个队列中都有 1323 名患者。我们对患者进行了为期 5 年的分析。使用 SGLT2i 可显著降低恶病质(HR 0.453,95% CI [0.286-0.718])、营养不良(HR 0.702,95% CI [0.547-0.900])、成人发育不良(HR 0.489,95% CI [0.345-0.693])和全因死亡率(HR 0.490,95% CI [0.423-0.568])的风险。这些发现要求开展更多研究,以确定 SGLT2i 是否确实能改善接受蒽环类疗法患者的营养状况和生存率。
{"title":"Sodium-Glucose Cotransporter 2 Inhibitors, Malnutrition, Cachexia, and Survival in Patients With Heart Failure With a History of Anthracycline Treatment.","authors":"Benjamin D Henson, Claudia A Bale-Neary, Ryan Mecaskey, Ogechi Gbujie, Michelle Zhan, Krishnasree Rao, Salvatore Carbone","doi":"10.1097/FJC.0000000000001620","DOIUrl":"10.1097/FJC.0000000000001620","url":null,"abstract":"<p><strong>Abstract: </strong>Patients undergoing anthracycline-based cancer treatments have an increased risk of heart failure or worsening preexisting heart failure as well as adverse metabolic outcomes such as malnutrition and cachexia. This retrospective study explored the impact of sodium-glucose cotransporter 2 inhibitors (SGLT2i) on these outcomes in patients with heart failure previously treated with anthracyclines. Using the TriNetX research network, we identified 1545 patients with a history of SGLT2i use and 17,681 patients without a history of SGLT2i use. We then performed 1:1 propensity score matching resulting in 1323 patients within each cohort. Patients were analyzed over a 5-year period. SGLT2i use was associated with significantly reduced risks of cachexia {hazard ratio (HR) 0.453, 95% confidence interval (CI) [0.286-0.718]}, malnutrition (HR 0.702, 95% CI [0.547-0.900]), adult failure to thrive (HR 0.489, 95% CI [0.345-0.693]), and all-cause mortality (HR 0.490, 95% CI [0.423-0.568]). These findings call for additional research to determine whether SGLT2i may indeed improve nutritional status and survival in patients with heart failure receiving anthracycline therapy.</p>","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":" ","pages":"486-489"},"PeriodicalIF":2.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141901866","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}
Pub Date : 2024-10-02DOI: 10.1097/FJC.0000000000001635
Antonio Abbate, Benjamin Van Tassell, Vlad Bogin, Roshanak Markley, Dmitry V Pevzner, Paul C Cremer, Imad A Meray, Dmitry V Privalov, Angela Taylor, Sergey A Grishin, Alina N Egorova, Ekaterina G Ponomar, Yan Lavrovsky, Mikhail Yu Samsonov
In a randomized double-blinded clinical trial of patients with ST segment elevation myocardial infarction (STEMI), goflikicept, an Interleukin-1 (IL-1) blocker, significantly reduced systemic inflammation, measured as the area-under-the-curve (AUC) for high-sensitivity C reactive protein (hsCRP) at 14 days. We report secondary analyses of biomarkers at 28 days, and cardiac function and clinical endpoints at 1 year. Patients received a single administration of goflikicept 80 mg (n=34), goflikicept 160 mg (n=34), or placebo (n=34). Both doses of goflikicept significantly reduced the AUC for hsCRP at 28 days compared with placebo, without statistically significant differences between the doses. There we no statistically significant differences between groups in the AUC for natriuretic peptides at 28 days. There were no significant differences between placebo, goflikicept 80 mg and 160 mg groups in deaths (2.9%, 2.9% and 0%), hospitalization for cardiovascular reasons (9.1%, 5.9%, and 0%), new-onset or progression of heart failure (9.1%, 5.9%, and 5.9%), and new or increased use of loop diuretics (24.2%, 14.7%, and 17.6%), nor in the number of patients with treatment emergent adverse events, with no treatment-related serious adverse events in any group. In conclusion, in patients with STEMI, IL-1 blockade with goflikicept 80 mg or 160 mg was well tolerated and associated with significant reduction of systemic inflammation. Further adequately powered studies are warranted to determine whether the reduction in systemic inflammation with goflikicept translates into a clinical benefit in patients with STEMI.
{"title":"Interleukin-1 blockade with RPH-104 (goflikicept) in patients with ST-segment elevation myocardial infarction (STEMI): secondary endpoints from an international, double blind, randomized, placebo-controlled, phase IIa study.","authors":"Antonio Abbate, Benjamin Van Tassell, Vlad Bogin, Roshanak Markley, Dmitry V Pevzner, Paul C Cremer, Imad A Meray, Dmitry V Privalov, Angela Taylor, Sergey A Grishin, Alina N Egorova, Ekaterina G Ponomar, Yan Lavrovsky, Mikhail Yu Samsonov","doi":"10.1097/FJC.0000000000001635","DOIUrl":"10.1097/FJC.0000000000001635","url":null,"abstract":"<p><p>In a randomized double-blinded clinical trial of patients with ST segment elevation myocardial infarction (STEMI), goflikicept, an Interleukin-1 (IL-1) blocker, significantly reduced systemic inflammation, measured as the area-under-the-curve (AUC) for high-sensitivity C reactive protein (hsCRP) at 14 days. We report secondary analyses of biomarkers at 28 days, and cardiac function and clinical endpoints at 1 year. Patients received a single administration of goflikicept 80 mg (n=34), goflikicept 160 mg (n=34), or placebo (n=34). Both doses of goflikicept significantly reduced the AUC for hsCRP at 28 days compared with placebo, without statistically significant differences between the doses. There we no statistically significant differences between groups in the AUC for natriuretic peptides at 28 days. There were no significant differences between placebo, goflikicept 80 mg and 160 mg groups in deaths (2.9%, 2.9% and 0%), hospitalization for cardiovascular reasons (9.1%, 5.9%, and 0%), new-onset or progression of heart failure (9.1%, 5.9%, and 5.9%), and new or increased use of loop diuretics (24.2%, 14.7%, and 17.6%), nor in the number of patients with treatment emergent adverse events, with no treatment-related serious adverse events in any group. In conclusion, in patients with STEMI, IL-1 blockade with goflikicept 80 mg or 160 mg was well tolerated and associated with significant reduction of systemic inflammation. Further adequately powered studies are warranted to determine whether the reduction in systemic inflammation with goflikicept translates into a clinical benefit in patients with STEMI.</p>","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142365364","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}