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Phosphodiesterase 5 and its inhibitors with ischemic heart disease: a Mendelian randomization analysis and a real-world study. 磷酸二酯酶 5 及其抑制剂与缺血性心脏病:孟德尔随机分析和真实世界研究。
IF 5.3 1区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-10-18 DOI: 10.1093/ehjcvp/pvae081
Jun Xiao, Naiqi Zhang, Ziting Gao, Yajing Wei, Hongye Wei, Ziyi Qiu, Kristina Sundquist, Jan Sundquist, Jianguang Ji, Wuqing Huang

Background: Accumulating studies reported that several phosphodiesterases (PDEs) inhibitors might have cardiovascular benefits.

Objectives: This study aimed to explore the relationship between genetically-predicted PDEs and ischemia heart disease via drug target Mendelian randomization (MR) approach, and then examine the effect of inhibitors of identified target on the outcomes by using real-world data.

Methods: In the two-sample MR study, the expression of genes encoding PDEs was used to proxy the level of PDEs and available expression quantitative trait loci (eQTLs) for each target gene were identified as the genetic instruments. The outcomes included coronary heart disease (CHD) and myocardial infarction (MI). In the real-world study, a retrospective cohort was conducted to compare the incidence of outcomes between PDE5 inhibitors and alprostadil use by linking Swedish nationwide registers.

Results: MR analyses identified two types of PDEs, PDE5 and PDE8, genetically-predicted expression in blood of the encoded genes was significantly associated with the risk of CHD (ORPDE5A = 1.22,95% CI = 1.06-1.40; ORPDE8A = 1.26,95% CI = 1.07-1.49) and MI (ORPDE5A = 1.27,95% CI = 1.09-1.48; ORPDE8A = 1.24,95% CI = 1.04-1.48). Notably, the highest expression of PDE5A was observed in artery aorta, which was also positively related to CHD (OR = 1.17,95% CI = 1.05-1.32) and MI (OR = 1.15,95% CI = 1.02-1.30). Real-world study provided supportive evidence that as compared to alprostadil use, PDE5 inhibitors use significantly reduced the incidence of CHD (adjusted HR = 0.70,95% CI = 0.66-0.73) and MI (adjusted HR = 0.79,95% CI = 0.73-0.84).

Conclusion: This study provided observational and genetic evidence about the protective role of PDE5 inhibition against ischemic heart disease, indicating the potential of these drugs to be repurposed for ischemia heart disease prevention and treatment.

背景:越来越多的研究表明,几种磷酸二酯酶(PDEs)抑制剂可能对心血管有益:本研究旨在通过药物靶点孟德尔随机化(MR)方法探讨基因预测的磷酸二酯酶与缺血性心脏病之间的关系,然后利用真实世界的数据研究确定靶点的抑制剂对结果的影响:在双样本 MR 研究中,使用编码 PDEs 的基因的表达来替代 PDEs 的水平,并为每个靶基因确定可用的表达定量性状位点(eQTLs)作为遗传工具。研究结果包括冠心病(CHD)和心肌梗死(MI)。在真实世界研究中,通过链接瑞典全国范围内的登记册,进行了一项回顾性队列研究,以比较 PDE5 抑制剂和阿普斯地尔使用之间的结果发生率:MR分析确定了两种类型的PDE,即PDE5和PDE8,编码基因在血液中的遗传预测表达与冠心病(ORPDE5A = 1.22,95% CI = 1.06-1.40;ORPDE8A = 1.26,95% CI = 1.07-1.49)和心肌梗死(ORPDE5A = 1.27,95% CI = 1.09-1.48;ORPDE8A = 1.24,95% CI = 1.04-1.48)的风险显著相关。值得注意的是,PDE5A 在动脉主动脉中的表达量最高,这也与冠心病(OR = 1.17,95% CI = 1.05-1.32)和心肌梗死(OR = 1.15,95% CI = 1.02-1.30)呈正相关。真实世界研究提供的支持性证据表明,与使用阿普斯地尔相比,使用PDE5抑制剂可显著降低冠心病(调整后HR = 0.70,95% CI = 0.66-0.73)和心肌梗死(调整后HR = 0.79,95% CI = 0.73-0.84)的发病率:这项研究为PDE5抑制剂对缺血性心脏病的保护作用提供了观察和遗传学证据,表明这些药物有可能被重新用于缺血性心脏病的预防和治疗。
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引用次数: 0
Design and Baseline Characteristics of the STRIDE Trial: evaluating Semaglutide in People with Symptomatic Peripheral Artery Disease and Type 2 Diabetes. STRIDE 试验的设计和基线特征:评估塞马鲁肽在有症状外周动脉疾病和 2 型糖尿病患者中的应用。
IF 5.3 1区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-10-18 DOI: 10.1093/ehjcvp/pvae071
Marc P Bonaca, Andrei-Mircea Catarig, Yasemin Hansen, Kim Houlind, Chethana Kalmady Ramesh, Bernhard Ludvik, Joakim Nordanstig, Neda Rasouli, Harald Sourij, Subodh Verma

Background: People with lower extremity peripheral artery disease (PAD) suffer from a high burden of symptoms and significant functional impairment. There are few therapies that improve function and reduce symptoms in this population. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have been shown to improve glycemic control, reduce body weight and reduce the risk of major adverse cardiovascular events, in people with atherosclerotic cardiovascular disease and type 2 diabetes (T2D).

Methods: STRIDE (NCT04560998) is a randomized, placebo-controlled, double-blind phase 3b trial evaluating 1 mg once-weekly subcutaneous semaglutide (GLP-1 RA) vs. placebo, in people with symptomatic PAD (Fontaine IIa claudication) and T2D. Eligible participants were ≥ 18 years, had hemodynamically stable PAD, had no planned intervention, and were not receiving a GLP-1 RA. The primary endpoint is change in maximum walking distance on a constant-load treadmill (CLT). Secondary endpoints include quality of life and cardiometabolic assessments.

Results: A total of 792 participants were randomized in 20 countries. Participants' median age was 68 and they had T2D for a median of 12 years. Risk factors included 25.6% current smokers, 87.9% with hypertension, and 42.7% with coronary heart disease. The mean BMI was 29.6 kg/m2 and mean HbA1C was 7.3%. Participants exhibited baseline functional impairment with a median maximum walking distance of 186 meters on a CLT.

Conclusion: STRIDE has enrolled participants with symptomatic PAD and T2D, frequent risk factors and comorbidities, and functional impairment. The trial will provide evidence for the functional outcomes with semaglutide in people with PAD and T2D.

背景:下肢外周动脉疾病(PAD)患者症状繁多,功能严重受损。目前能改善这类患者功能和减轻症状的疗法很少。胰高血糖素样肽-1受体激动剂(GLP-1 RAs)已被证明可改善动脉粥样硬化性心血管疾病和2型糖尿病(T2D)患者的血糖控制、减轻体重并降低主要不良心血管事件的风险:STRIDE(NCT04560998)是一项随机、安慰剂对照、双盲的3b期试验,评估有症状的PAD(方丹IIa跛行)和T2D患者每周一次皮下注射1毫克司马鲁肽(GLP-1 RA)与安慰剂的对比。符合条件的参与者年龄≥ 18 岁,具有血液动力学稳定的 PAD,未计划进行干预,且未接受 GLP-1 RA 治疗。主要终点是恒定负荷跑步机(CLT)上最大步行距离的变化。次要终点包括生活质量和心脏代谢评估:共有 792 名参与者在 20 个国家接受了随机治疗。参与者的年龄中位数为 68 岁,患 T2D 的时间中位数为 12 年。风险因素包括 25.6% 的人目前吸烟,87.9% 的人患有高血压,42.7% 的人患有冠心病。平均体重指数为 29.6 kg/m2,平均 HbA1C 为 7.3%。参与者表现出基线功能障碍,CLT 最大步行距离中位数为 186 米:结论:STRIDE试验招募了有症状的PAD和T2D患者,他们都有常见的风险因素和合并症,并存在功能障碍。该试验将为semaglutide在PAD和T2D患者中的功能性结果提供证据。
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引用次数: 0
Impact of ticagrelor with or without aspirin on total and recurrent bleeding and ischemic events after percutaneous coronary intervention: A sub-study of the TWILIGHT trial. 替卡格雷联合或不联合阿司匹林对经皮冠状动脉介入治疗后总出血、复发性出血和缺血性事件的影响:TWILIGHT 试验的一项子研究。
IF 5.3 1区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-10-17 DOI: 10.1093/ehjcvp/pvae080
Usman Baber, Davide Cao, Timothy Collier, Samantha Sartori, George Dangas, Dominick J Angiolillo, Birgit Vogel, Vijay Kunadian, Carlo Briguori, David J Cohen, Dariusz Dudek, C Michael Gibson, Robert Gil, Kurt Huber, Upendra Kaul, Ran Kornowski, Mitchell W Krucoff, Shamir Mehta, David J Moliterno, E Magnus Ohman, Javier Escaned, Gennaro Sardella, Samin K Sharma, Richard Shlofmitz, Giora Weisz, Bernhard Witzenbichler, P Gabriel Steg, Stuart Pocock, Roxana Mehran

Aims: In standard time-to-first event analysis, early aspirin discontinuation followed by ticagrelor monotherapy has been shown to reduce bleeding without increasing ischemic complications compared with ticagrelor plus aspirin after percutaneous coronary intervention (PCI). We evaluated whether these treatment effects are preserved when recurrent events are considered.

Methods and results: In this TWILIGHT trial post hoc analysis, we assessed the effects of ticagrelor monotherapy on the total number of events that occurred over the 12-month follow-up among 7 119 high-risk patients randomized to aspirin or placebo in addition to ticagrelor at 3 months post-PCI if event-free and adherent to treatment. There were 391 patients with at least one Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding (primary endpoint). Of those, 28 (7.2%) had a recurrent event. The total number of BARC 2, 3, or 5 bleeding events were 148 in the ticagrelor monotherapy arm compared with 278 with ticagrelor plus aspirin arm (p < 0.001). Among 272 patients with at least one key secondary ischemic endpoint (all-cause death, myocardial infarction, or stroke), 37 (13.6%) sustained a recurrent event. Total ischemic events were similar (155 vs 159) in the two groups.

Conclusions: Among selected high-risk patients who underwent PCI and completed 3 months of dual antiplatelet therapy followed by ticagrelor with or without aspirin, recurrent bleeding was less common than recurrent ischemic events over 12 months. Analysis of total events indicates that ticagrelor monotherapy continues to be more effective than ticagrelor plus aspirin in reducing bleeding without a signal of ischemic harm.

目的:在标准的首次事件发生时间分析中,与经皮冠状动脉介入治疗(PCI)后使用替卡格雷加阿司匹林相比,早期停用阿司匹林后使用替卡格雷单药治疗可减少出血而不增加缺血性并发症。我们评估了在考虑复发事件的情况下,这些治疗效果是否得以保留:在这项 TWILIGHT 试验的事后分析中,我们评估了替卡格雷单药治疗对 7 119 名高风险患者在 12 个月随访期间发生的事件总数的影响,这些患者在经皮冠状动脉介入术后 3 个月无事件且坚持治疗的情况下,除替卡格雷外,还随机接受了阿司匹林或安慰剂治疗。有 391 名患者至少发生过一次出血学术研究联盟 (BARC) 2、3 或 5 型出血(主要终点)。其中 28 例(7.2%)出现复发。替卡格雷单药治疗组的 BARC 2、3 或 5 型出血事件总数为 148 例,而替卡格雷加阿司匹林治疗组为 278 例(P,结论):在接受 PCI 并完成 3 个月双联抗血小板治疗后再接受替卡格雷加或不加阿司匹林治疗的选定高危患者中,12 个月内复发出血比复发缺血事件少见。对总事件的分析表明,在减少出血方面,替卡格雷单药治疗仍然比替卡格雷加阿司匹林治疗更有效,而且没有缺血性伤害的信号。
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引用次数: 0
Inotropes and mortality in patients with cardiogenic shock: an instrumental variable analysis from the SWEDEHEART registry. 心源性休克患者的肌力药物和死亡率:来自 SWEDEHEART 登记的工具变量分析。
IF 5.3 1区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-10-16 DOI: 10.1093/ehjcvp/pvae078
Petur Petursson, Thorsteinn Gudmundsson, Truls Råmunddal, Oskar Angerås, Araz Rawshani, Moman A Mohammad, Jonas Persson, Joakim Alfredsson, Robin Hofmann, Tomas Jernberg, Ole Fröbert, David Erlinge, Björn Redfors, Elmir Omerovic

Background: The use of inotropic agents in treating cardiogenic shock (CS) remains controversial. This study investigates the effect of inotropes on 30-day mortality in CS patients using data from the SWEDEHEART registry (The Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies).

Methods: Data were sourced from the national SWEDEHEART registry for all CS patients in Sweden from 2000 to 2022. The primary endpoint was 30-day all-cause mortality. We employed multilevel Cox proportional-hazards regression with instrumental variable and inverse probability weighting propensity score to adjust for confounders. The treatment-preference instrument was the quintile of preference for inotrope use at the treating hospital.

Results: A total of 16 214 patients (60.5% men, 39.5% women) were included; 23.5% had diabetes, 10.2% had a previous myocardial infarction (MI), and 13.8% had previous heart failure (HF). The median age was 70 years (IQR; 19), with 66.4% over 70. Acute coronary syndrome (ACS) caused CS in 82.9%. Inotropes were administered to 43.8% of patients, while 56.2% did not receive them. There were 7 875 (48.1%) deaths. Patients treated with inotropes were, on average, two years younger and more likely to have ACS, while those not treated had more previous MI and were less likely to undergo PCI. The number of CS cases decreased by 12% per year (Ptrend < 0.001), and inotrope use increased by 5% per year (Ptrend < 0.001). Unadjusted mortality in CS rose by 2% per calendar year (Ptrend < 0.001). Inotropes were associated with higher mortality (adjusted HR 1.72; 95% CI 1.26-2.35; P = 0.001), with significant interactions between inotrope treatment, age, and diagnosis (Pinteraction < 0.001 and Pinteraction = 0.018).

Conclusions: In this observational study, inotropes were linked to higher mortality in CS patients, particularly those younger than 70. While CS cases decreased, inotrope use and mortality increased in Sweden.

背景:使用肌力药物治疗心源性休克(CS)仍存在争议。本研究利用 SWEDEHEART 登记系统(瑞典心脏病循证治疗评估网络系统)的数据,调查了肌注药物对 CS 患者 30 天死亡率的影响:方法:数据来源于瑞典国家SWEDEHEART登记处2000年至2022年所有CS患者的数据。主要终点是 30 天全因死亡率。我们采用带有工具变量和反概率加权倾向评分的多层次 Cox 比例危险回归来调整混杂因素。治疗偏好工具是治疗医院对肌注药物使用偏好的五分位数:共纳入 16 214 名患者(60.5% 为男性,39.5% 为女性);23.5% 的患者患有糖尿病,10.2% 的患者既往患有心肌梗死(MI),13.8% 的患者既往患有心力衰竭(HF)。中位年龄为 70 岁(IQR; 19),66.4% 的患者超过 70 岁。82.9%的患者因急性冠状动脉综合征(ACS)导致CS。43.8%的患者接受了肌注,56.2%的患者没有接受肌注。共有 7 875 人(48.1%)死亡。接受肌注治疗的患者平均年轻两岁,更有可能发生急性冠状动脉综合征,而未接受肌注治疗的患者既往有更多心肌梗死病史,接受 PCI 治疗的可能性更小。CS病例数每年减少12%(Ptrend结论):在这项观察性研究中,肌注与 CS 患者死亡率升高有关,尤其是那些年龄小于 70 岁的患者。虽然瑞典的 CS 病例有所减少,但肌注药物的使用和死亡率却有所上升。
{"title":"Inotropes and mortality in patients with cardiogenic shock: an instrumental variable analysis from the SWEDEHEART registry.","authors":"Petur Petursson, Thorsteinn Gudmundsson, Truls Råmunddal, Oskar Angerås, Araz Rawshani, Moman A Mohammad, Jonas Persson, Joakim Alfredsson, Robin Hofmann, Tomas Jernberg, Ole Fröbert, David Erlinge, Björn Redfors, Elmir Omerovic","doi":"10.1093/ehjcvp/pvae078","DOIUrl":"https://doi.org/10.1093/ehjcvp/pvae078","url":null,"abstract":"<p><strong>Background: </strong>The use of inotropic agents in treating cardiogenic shock (CS) remains controversial. This study investigates the effect of inotropes on 30-day mortality in CS patients using data from the SWEDEHEART registry (The Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies).</p><p><strong>Methods: </strong>Data were sourced from the national SWEDEHEART registry for all CS patients in Sweden from 2000 to 2022. The primary endpoint was 30-day all-cause mortality. We employed multilevel Cox proportional-hazards regression with instrumental variable and inverse probability weighting propensity score to adjust for confounders. The treatment-preference instrument was the quintile of preference for inotrope use at the treating hospital.</p><p><strong>Results: </strong>A total of 16 214 patients (60.5% men, 39.5% women) were included; 23.5% had diabetes, 10.2% had a previous myocardial infarction (MI), and 13.8% had previous heart failure (HF). The median age was 70 years (IQR; 19), with 66.4% over 70. Acute coronary syndrome (ACS) caused CS in 82.9%. Inotropes were administered to 43.8% of patients, while 56.2% did not receive them. There were 7 875 (48.1%) deaths. Patients treated with inotropes were, on average, two years younger and more likely to have ACS, while those not treated had more previous MI and were less likely to undergo PCI. The number of CS cases decreased by 12% per year (Ptrend < 0.001), and inotrope use increased by 5% per year (Ptrend < 0.001). Unadjusted mortality in CS rose by 2% per calendar year (Ptrend < 0.001). Inotropes were associated with higher mortality (adjusted HR 1.72; 95% CI 1.26-2.35; P = 0.001), with significant interactions between inotrope treatment, age, and diagnosis (Pinteraction < 0.001 and Pinteraction = 0.018).</p><p><strong>Conclusions: </strong>In this observational study, inotropes were linked to higher mortality in CS patients, particularly those younger than 70. While CS cases decreased, inotrope use and mortality increased in Sweden.</p>","PeriodicalId":11982,"journal":{"name":"European Heart Journal - Cardiovascular Pharmacotherapy","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461062","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}
引用次数: 0
Role of PCSK9 Inhibitors in Venous Thromboembolism: Current Evidence and Unmet Clinical Needs. PCSK9 抑制剂在静脉血栓栓塞症中的作用:当前证据和未满足的临床需求。
IF 5.3 1区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-10-15 DOI: 10.1093/ehjcvp/pvae076
Marco Zuin, Alberto Corsini, Chiara Dalla Valle, Catia De Rosa, Alessandro Maloberti, Marco Mojoli, Massimiliano Rizzo, Francesco Ciccirillo, Alfredo Madrid, Carmine Riccio, Massimo Grimaldi, Furio Colivicchi, Fabrizio Oliva, Pier Luigi Temporelli

Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) have recently emerged as promising therapeutic agents for lowering low-density lipoprotein cholesterol and reducing the risk of cardiovascular events. Moreover, preliminary evidence from randomized controlled trials (RCTs) suggests that PCSK9i may also offer beneficial effects for patients following venous thromboembolism (VTE), with the most significant reductions in risk appearing over time, particularly beyond the first year of treatment. However, there is a lack of randomized controlled data supporting their efficacy and safety in conjunction with standard anticoagulation therapy. This article aims to critically evaluate the existing evidence for the use of PCSK9i as a complementary therapy for VTE risk reduction, while also identifying unmet clinical and research needs and proposing potential strategies to address these knowledge gaps.

近来,前蛋白转化酶亚基酶/kexin 9 型抑制剂(PCSK9i)已成为降低低密度脂蛋白胆固醇和减少心血管事件风险的有前途的治疗药物。此外,来自随机对照试验(RCTs)的初步证据表明,PCSK9i 还能为静脉血栓栓塞(VTE)患者带来益处,随着时间的推移,尤其是治疗第一年后,风险会出现最显著的降低。然而,目前还缺乏随机对照数据来支持其与标准抗凝疗法相结合的疗效和安全性。本文旨在批判性地评估将 PCSK9i 用作降低 VTE 风险的辅助疗法的现有证据,同时确定尚未满足的临床和研究需求,并提出解决这些知识缺口的潜在策略。
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引用次数: 0
Hypokalaemia in patients with type 2 diabetes and chronic kidney disease: the effect of finerenone - a FIDELITY analysis. 2 型糖尿病和慢性肾病患者的低钾血症:非诺酮的影响 - FIDELITY 分析。
IF 5.3 1区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-10-08 DOI: 10.1093/ehjcvp/pvae074
Bertram Pitt, Rajiv Agarwal, Stefan D Anker, Peter Rossing, Luis Ruilope, Charles A Herzog, Barry Greenberg, Roberto Pecoits-Filho, Marc Lambelet, Robert Lawatscheck, Andrea Scalise, Gerasimos Filippatos

Aims: Hypokalaemia is associated with cardiovascular events and mortality in patients with chronic kidney disease (CKD). This exploratory FIDELITY analysis, a prespecified pooled patient-dataset from FIDELIO-DKD and FIGARO-DKD, investigated the incidence and effect of hypokalaemia in patients with CKD and type 2 diabetes (T2D) treated with finerenone vs. placebo.

Methods: Outcomes include the incidence of treatment-emergent hypokalaemia (serum potassium < 4.0 or < 3.5 mmol/L) and the effect of finerenone on cardiovascular composite outcome (cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, or hospitalization for heart failure) and arrhythmia composite outcome (new diagnosis of atrial fibrillation/atrial flutter, hospitalization due to arrhythmia, or sudden cardiac death) by baseline serum potassium subgroups.

Results: In the FIDELITY population, treatment-emergent hypokalaemia with serum potassium < 4.0 and < 3.5 mmol/L occurred in 41.1% and 7.5%, respectively. Hazards of cardiovascular and arrhythmia composite outcomes were higher in patients with baseline serum potassium < 4.0 vs. 4.0-4.5 mmol/L (hazard ratio [HR] 1.16; 95% confidence interval [CI] 1.02-1.32, P = 0.022 and HR 1.20; 95% CI 1.00-1.44, P = 0.055, respectively). Finerenone reduced the incidence of hypokalaemia with serum potassium < 4.0 mmol/L (HR 0.63; 95% CI 0.60-0.66) and < 3.5 mmol/L (HR 0.46; 95% CI 0.40-0.53) vs. placebo. Finerenone lessened the hazard of cardiovascular and arrhythmia events vs. placebo, irrespective of baseline serum potassium.

Conclusion: A substantial proportion of patients with CKD and T2D experienced hypokalaemia, which was associated with an increased hazard of adverse cardiovascular outcomes. Finerenone reduced the incidence of hypokalaemia. Finerenone reduced the hazard of cardiovascular and arrhythmia outcomes irrespective of serum potassium subgroups. Clinical trials registration: FIDELIO-DKD and FIGARO-DKD are registered with ClinicalTrials.gov, numbers NCT02540993 and NCT02545049, respectively (funded by Bayer AG).

目的:低钾血症与慢性肾脏病 (CKD) 患者的心血管事件和死亡率有关。这项探索性 FIDELITY 分析是一项来自 FIDELIO-DKD 和 FIGARO-DKD 的预设集合患者数据集,研究了接受非格列酮与安慰剂治疗的 CKD 和 2 型糖尿病(T2D)患者低钾血症的发生率及其影响:结果包括治疗引发的低血钾(血清钾结果)的发生率:结果:在 FIDELITY 研究人群中,治疗引发的低血钾(血清钾)发生率较高:相当一部分慢性肾脏病和终末期糖尿病患者出现低钾血症,这与不良心血管后果的风险增加有关。非格列酮能降低低钾血症的发生率。无论血清钾分组如何,非奈酮都能降低心血管和心律失常的危害。临床试验注册:FIDELIO-DKD 和 FIGARO-DKD 已在 ClinicalTrials.gov 注册,编号分别为 NCT02540993 和 NCT02545049(由拜耳公司资助)。
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引用次数: 0
The dual endothelin-1 antagonist aprocitentan alleviates mitochondrial oxidative stress in human cardiac fibroblasts. 双重内皮素-1 拮抗剂阿普西坦能缓解人心脏成纤维细胞的线粒体氧化应激
IF 5.3 1区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-10-04 DOI: 10.1093/ehjcvp/pvae050
Fahimeh Varzideh, Stanislovas S Jankauskas, Urja Jain, Lauren Soderquist, Esther Densu Agyapong, Urna Kansakar, Gaetano Santulli
{"title":"The dual endothelin-1 antagonist aprocitentan alleviates mitochondrial oxidative stress in human cardiac fibroblasts.","authors":"Fahimeh Varzideh, Stanislovas S Jankauskas, Urja Jain, Lauren Soderquist, Esther Densu Agyapong, Urna Kansakar, Gaetano Santulli","doi":"10.1093/ehjcvp/pvae050","DOIUrl":"10.1093/ehjcvp/pvae050","url":null,"abstract":"","PeriodicalId":11982,"journal":{"name":"European Heart Journal - Cardiovascular Pharmacotherapy","volume":" ","pages":"566-568"},"PeriodicalIF":5.3,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11450266/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141558380","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}
引用次数: 0
New ways of mitigating aldosterone in cardiorenal disease. 减轻心肾疾病中醛固酮的新方法。
IF 5.3 1区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-10-04 DOI: 10.1093/ehjcvp/pvae049
Felix Götzinger, Michael Kunz, Lucas Lauder, Michael Böhm, Felix Mahfoud

Steroidal mineralocorticoid receptor antagonists (MRAs) bind to the mineralocorticoid receptor and antagonize the effects of aldosterone, which contributes to the development and progression of cardio- and renovascular diseases. Guidelines recommend steroidal MRAs in patients with heart failure with reduced or mildly reduced ejection fraction, as they reduce morbidity and mortality. In heart failure with preserved ejection fraction, MRAs have not convincingly shown to improve prognosis. Steroidal MRAs delay the progression of chronic kidney disease, reduce proteinuria and lower blood pressure in resistant hypertension but can induce hyperkalaemia. Due to their limited selectivity to the mineralocorticoid receptor, steroidal MRAs can cause significant adverse effects, i.e. libido loss, erectile dysfunction, gynaecomastia, and amenorrhoea, leading to low rates of persistance. Against this background, new avenues for developing non-steroidal, selective (ns)MRAs and aldosterone-synthase inhibitors have been taken. Finerenone has been shown to delay the progression of diabetic nephropathy and lower the incidence of heart failure hospitalizations in patients with chronic kidney disease and diabetes compared with placebo. Finerenone has therefore been recommended by the 2023 European Society of Cardiology Guidelines for the management of diabetes in patients with type 2 diabetes and chronic kidney disease. Further randomized controlled trials assessing the safety and effectiveness of finerenone in patients with heart failure are currently ongoing. Esaxerenone provides antihypertensive effects and has been approved for the treatment of hypertension in Japan. Baxdrostat and lorundostat, novel selective aldosterone-synthase inhibitors, are currently under investigation. In phase II trials, baxdrostat and lorundostat were safe and effective in lowering blood pressure in resistant hypertension. In this review, we summarize and critically discuss the evidence for new drugs mitigating aldosterone in heart failure, hypertension, and chronic kidney disease.

类固醇类矿化皮质激素受体拮抗剂(MRA)与矿化皮质激素受体结合,拮抗醛固酮的作用,而醛固酮会导致心脑血管疾病的发生和发展。对于射血分数降低或轻度降低的心力衰竭患者,指南推荐使用类固醇 MRA,因为它们可以降低发病率和死亡率。对于射血分数保留的心衰患者,MRA 并未令人信服地改善预后。类固醇类 MRA 可延缓慢性肾病的进展,减少蛋白尿,降低抵抗性高血压患者的血压,但会诱发高钾血症。由于类固醇 MRA 对矿物质皮质激素受体的选择性有限,它们可能会引起明显的不良反应,如性欲减退、勃起功能障碍、妇科肿瘤和闭经,导致持续用药率低。在此背景下,开发非甾体、选择性(ns)MRA 和醛固酮合成酶抑制剂的新途径应运而生。与安慰剂相比,非格列酮能延缓糖尿病肾病的进展,降低慢性肾病和糖尿病患者心力衰竭的住院率。因此,《2023 年欧洲心脏病学会指南》推荐使用非格列酮来治疗 2 型糖尿病和慢性肾病患者的糖尿病。目前正在进行进一步的随机对照试验,评估非奈瑞酮对心力衰竭患者的安全性和有效性。依沙萘酮具有降压作用,在日本已被批准用于治疗高血压。目前正在研究新型选择性醛固酮合成酶抑制剂 Baxdrostat 和 lorundostat。在 II 期试验中,Baxdrostat 和 Lorundostat 在降低抵抗性高血压患者的血压方面安全有效。在这篇综述中,我们总结并认真讨论了减轻心力衰竭、高血压和慢性肾病患者醛固酮的新药证据。
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引用次数: 0
The impact of sodium-glucose cotransporter 2 inhibitors in post-myocardial infarction management: insights from EMPACT-MI and DAPA-MI trials. SGLT2 抑制剂对心肌梗死后管理的影响:来自 EMPACT-MI 和 DAPA-MI 试验的启示。
IF 5.3 1区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-10-04 DOI: 10.1093/ehjcvp/pvae053
Eri Toda Kato, Koji Hasegawa, Koh Ono
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引用次数: 0
Diltiazem reduces levels of NT-proBNP and improves symptoms compared with metoprolol in patients with permanent atrial fibrillation. 与美托洛尔相比,地尔硫卓能降低永久性心房颤动患者的 NT-proBNP 水平并改善症状。
IF 5.3 1区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-10-04 DOI: 10.1093/ehjcvp/pvae032
Katrine Enge, Arnljot Tveit, Steve Enger, Sophia Onarheim, Are Hugo Pripp, Peter Selmer Rønningen, Magnar Gangås Solberg, Rune Byrkjeland, Kristoffer Andresen, Anders Halsen, Hanne Aaserud Aulie, Trude Steinsvik, Christian Hall, Sara Reinvik Ulimoen

Aims: Short-term treatment with calcium channel blockers lowers levels of N-terminal pro B-type natriuretic peptide (NT-proBNP) and reduces rhythm-related symptoms compared to treatment with beta-blockers. The aim of this study was to compare the effects of metoprolol and diltiazem for rate control in patients with permanent atrial fibrillation (AF) after 6 months.

Methods and results: Men and women with permanent AF and preserved left ventricular systolic function were randomized to receive either diltiazem 360 mg or metoprolol 100 mg once daily. The primary endpoint was the level of NT-proBNP after a 6-month treatment period. Secondary endpoints included heart rate, rhythm-related symptoms and exercise capacity. A total of 93 patients (mean age 71 ± 7 years, 28 women) were randomized. After 6-months' treatment, mean levels of NT-proBNP decreased in the diltiazem group and increased in the metoprolol group, with a significant between-group difference (409.8 pg/mL, 95% CI: 230.6-589.1, P < 0.001). Treatment with diltiazem significantly reduced rhythm-related symptoms compared to baseline, but no change was observed in the metoprolol group. Diltiazem and metoprolol had similar effects on heart rate and exercise capacity.

Conclusion: Diltiazem reduced NT-proBNP levels and improved rhythm-related symptoms. Metoprolol increased peptide levels but had no impact on symptoms despite similar heart rate reduction. Non-dihydropyridine calcium channel blockers should be considered more often for rate control in permanent AF.

目的:与β-受体阻滞剂相比,钙通道阻滞剂的短期治疗可降低N-末端前B型钠尿肽(NT-proBNP)的水平并减轻心律相关症状。本研究旨在比较美托洛尔和地尔硫卓在 6 个月后对永久性心房颤动患者进行心率控制的长期效果:对患有永久性心房颤动且左心室收缩功能保留的男性和女性患者进行随机分组,分别给予地尔硫卓 360 毫克或美托洛尔 100 毫克,每天一次。主要终点是治疗 6 个月后的 NT-proBNP 水平。次要终点包括心率、心律相关症状和运动能力。共有 93 名患者(平均年龄 71 ± 7 岁,28 名女性)接受了随机治疗。经过 6 个月的治疗,地尔硫卓组的 NT-proBNP 平均水平有所下降,而美托洛尔组则有所上升,组间差异显著(409.8 pg/mL,95% CI:230.6 - 589.1,PC结论:地尔硫卓降低了NT-proBNP水平,改善了心律相关症状。美托洛尔能提高肽水平,但对症状没有影响,尽管心率降低的情况相似。在控制永久性心房颤动的心率时,应更多地考虑使用非二氢吡啶类钙通道阻滞剂。
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引用次数: 0
期刊
European Heart Journal - Cardiovascular Pharmacotherapy
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