Pharmacology

药理学
  • 文章类型: Editorial
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  • 文章类型: Journal Article
    背景:在过去的十年中,我们对小儿AKI的认识有了实质性进展.尽管取得了这些进展,我们对儿童AKI的药理学和营养治疗的理解仍存在很大差距.
    方法:在第26届急性疾病质量倡议(ADQI)共识会议上,一个多学科专家组审查了证据,并使用改良的Delphi程序,就儿科AKI药物和营养管理方面的差距和进展的建议达成共识.讨论了当前的证据以及差距和机会,并总结了建议。
    结果:形成了两个共识声明。(1)高价值,应选择消除肾脏的药物来详细表征其药代动力学,药效学,和药物-“组学”在整个发育连续体中的患病儿童中。这将允许以改善患者护理为目标的实时建模的优化。肾毒素管理将被确定为组织优先事项,并得到必要资源和基础设施的支持。(2)以患者为中心的结果(功能状态,生活质量,和最佳生长和发育)必须推动有针对性的营养干预措施,以优化短期和长期营养。人体测量的急性和慢性变化的措施,身体成分,物理功能,代谢控制应纳入营养评估。
    结论:与成年患者相比,新生儿和儿童具有独特的代谢和生长参数。需要对多学科转化研究工作进行战略投资,以填补患有AKI或处于AKI风险的儿童在营养需求和药理学最佳实践方面的知识空白。
    BACKGROUND: In the past decade, there have been substantial advances in our understanding of pediatric AKI. Despite this progress, large gaps remain in our understanding of pharmacology and nutritional therapy in pediatric AKI.
    METHODS: During the 26th Acute Disease Quality Initiative (ADQI) Consensus Conference, a multidisciplinary group of experts reviewed the evidence and used a modified Delphi process to achieve consensus on recommendations for gaps and advances in care for pharmacologic and nutritional management of pediatric AKI. The current evidence as well as gaps and opportunities were discussed, and recommendations were summarized.
    RESULTS: Two consensus statements were developed. (1) High-value, kidney-eliminated medications should be selected for a detailed characterization of their pharmacokinetics, pharmacodynamics, and pharmaco-\"omics\" in sick children across the developmental continuum. This will allow for the optimization of real-time modeling with the goal of improving patient care. Nephrotoxin stewardship will be identified as an organizational priority and supported with necessary resources and infrastructure. (2) Patient-centered outcomes (functional status, quality of life, and optimal growth and development) must drive targeted nutritional interventions to optimize short- and long-term nutrition. Measures of acute and chronic changes of anthropometrics, body composition, physical function, and metabolic control should be incorporated into nutritional assessments.
    CONCLUSIONS: Neonates and children have unique metabolic and growth parameters compared to adult patients. Strategic investments in multidisciplinary translational research efforts are required to fill the knowledge gaps in nutritional requirements and pharmacological best practices for children with or at risk for AKI.
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  • 文章类型: Journal Article
    Conventional synthetic (cs) and targeted synthetic (ts) disease-modifying antirheumatic drugs (DMARD) have potential interactions with a multitude of drugs. Furthermore, they sometimes have a lower therapeutic index, particularly in cases of limited organ functions. The aim of this work was to establish evidence-based recommendations on the therapeutic use of DMARDs in the context of drug interactions and dosage recommendations. A systematic literature search was carried out on the issue of drug interactions and dosages in cases of patients with limited kidney function and higher age and suffering from rheumatoid arthritis. A total of 2756 scientific publications were screened and 154 selected of which 68 were scrutinized in detail. Furthermore, the respective product information was also analyzed. A multitude of possible interactions of synthetic DMARDs with different drugs were detected, which were then assessed with respect to the clinical significance and consequences. A consensus process led to making recommendations with which the interactions were classified: A: dangerous combination, B: avoid combination (if possible, pausing DMARD treatment), C: possible combination requiring increased monitoring and potential adjustments in dosage and D: pharmacological interaction without relevance in DMARD standard doses. Apart from that dosage recommendations were established for each csDMARD and tsDMARD depending on kidney function and age. There are 3 primary recommendations and 11 core recommendations on interactions and dosages of csDMARDs and tsDMARDs meant as a practical help for therapeutic decision making and to improve safety in the treatment of rheumatoid arthritis.
    UNASSIGNED: Konventionelle synthetische („conventional synthetic“ [cs]) und gezielte synthetische („targeted synthetic“ [ts]) DMARDs haben potenzielle Wechselwirkungen mit einer Vielzahl von Medikamenten. Darüber hinaus haben sie insbesondere bei eingeschränkten Organfunktionen teilweise eine geringe therapeutische Breite. Ziel der Arbeit war eine systematische Erarbeitung von evidenzbasierten Empfehlungen zur Therapie mit DMARDs im Kontext von Arzneimittelinteraktionen und Dosierungsempfehlungen. Es wurde eine systematische Literaturrecherche zur Frage nach Wechselwirkungen sowie Dosierungen bei eingeschränkter Nierenfunktion und höherem Lebensalter bei rheumatoider Arthritis durchgeführt. Insgesamt wurden 2756 wissenschaftliche Publikationen gescreent und 154 ausgewählt, wobei 68 Publikationen in eine detaillierte Analyse eingingen. Darüber hinaus wurden die Informationen der jeweiligen Fachinformationen analysiert. Es fand sich eine Vielzahl von möglichen Wechselwirkungen von synthetischen DMARDs mit verschiedenen Medikamenten, welche bezüglich klinischer Bedeutung und Konsequenz bewertet wurden. In einem Konsensprozess wurden Empfehlungen erarbeitet, wobei eine Graduierung der Wechselwirkungen erfolgte: A: gefährliche Kombination, B: Kombination meiden (wenn möglich DMARD-Pause), C: mögliche Kombination mit erhöhtem Überwachungsbedarf und evtl. Dosisanpassung, D: pharmakologische Interaktion ohne Relevanz in Standarddosierungen des DMARD. Es wurden darüber hinaus Dosierungsempfehlungen nach Nierenfunktion und Alter für jedes cs- und tsDMARD erarbeitet. Drei übergeordnete Empfehlungen und 11 Kernempfehlungen zu Wechselwirkungen und Dosierung von cs- und tsDMARDs sollen praktische Hilfestellung für therapeutische Entscheidungen geben und die Sicherheit der Therapie der rheumatoiden Arthritis verbessern.
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  • 文章类型: Journal Article
    目的:第3工作组的目的是探讨材料和抗再吸收药物相关因素对植入牙科临床和生物学结果及并发症的影响。重点关注的问题是(a)钛(合金)以外的植入物材料,解决了(b)经粘膜基台材料和(c)影响骨代谢的药物。
    方法:三个系统综述构成了第3组讨论的基础。根据系统评价结果,通过小组共识制定共识声明和临床建议。还传达了患者的观点和对未来研究的建议。然后根据全体会议的要求进行进一步讨论和修改后,提出并接受了这些建议。
    结果:氧化锆是钛的有效替代品,可用作植入物和透粘膜组件的材料,允许软组织和硬组织与临床结果整合-通过植入物存活来识别,边缘骨质流失和种植体周围探查深度-与胫骨相似,最长为5年。然而,氧化锆植入物的大多数证据是基于限制适应症范围的1件式植入物。此外,根据专家意见,在美学区,氧化锆透粘膜成分可能是首选。在接受低剂量双膦酸盐治疗的患者中,早期植入物失败率没有增加,而对长期影响的研究仍然很少。尽管尚未得到充分解决,低剂量denosumab可以预期类似的结果.当考虑在接受低剂量ARD治疗的患者中放置植入物时,不建议休药期。然而,特定的治疗窗口,应考虑累积剂量和给药时间。必须获得种植体周围的支持性护理,以防止种植体周围炎相关的药物相关的颌骨坏死(MRONJ)或种植体相关的后遗症(IRS)。在接受低剂量抗吸收药物(ARD)治疗的患者中,与植入物放置相关的并发症风险很高,在这一特定人群中的植入程序应在综合的多学科中心严格处理。最后,在低或高剂量ARD之前,不应移除健康的牙科植入物。
    结论:在选定的适应症中,氧化锆植入物可以替代钛植入物。然而,目前的证据仍然有限,特别是2件植入物的设计。低剂量ARD的给药对早期植入结果没有任何负面影响,但建议谨慎随访和支持治疗,以预防MRONJ和IRS植入。必须在综合的多学科中心严格考虑大剂量患者的植入物放置。
    OBJECTIVE: The aim of Working Group 3 was to address the influence of both material- and anti-resorptive drug- related factors on clinical and biological outcomes and complications in implant dentistry. Focused questions were addressed on (a) implant materials other than titanium (alloy)s, (b) transmucosal abutment materials and (c) medications affecting bone metabolism were addressed.
    METHODS: Three systematic reviews formed the basis for discussion in Group 3. Consensus statements and clinical recommendations were formulated by group consensus based on the findings of the systematic reviews. Patient perspectives and recommendations for future research were also conveyed. These were then presented and accepted following further discussion and modifications as required by the plenary.
    RESULTS: Zirconia is a valid alternative to titanium as material for implant and transmucosal components, allowing soft and hard tissue integration with clinical outcomes-identified by implant survival, marginal bone loss and peri-implant probing depths-up to 5-years comparable to titatnium. However, most of the evidence for zirconia implants is based on 1-piece implants limiting the indication range. Furthermore, based on expert opinion, zirconia transmucosal components might be preferred in the esthetic zone. In patients receiving low-dose bisphosphonate therapy, the rate of early implant failure is not increased, while the long-term effects remain poorly studied. Although it has not been sufficiently addressed, similar outcomes can be expected with low-dose denosumab. A drug holiday is not recommended when considering implant placement in patients treated with low-dose ARD. However, the specific therapeutic window, the cumulative dose and the administration time should be considered. Access to peri-implant supportive care is mandatory to prevent peri-implantitis-related medication-related osteonecrosis of the jaw (MRONJ) or implant-related sequestra (IRS). In patients receiving low-dose anti-resorptive drugs (ARD) therapy, the risk of complications related to implant placement is high, and implant procedures in this specific population should be strictly treated in a comprehensive multidisciplinary center. Finally, healthy dental implants should not be removed before low or high-dose ARD.
    CONCLUSIONS: Zirconia implants can be an alternative to titanium implants in selected indications. However, the current state of evidence remains limited, especially for 2-piece implant designs. Administration of low-dose ARD did not show any negative impact on early implant outcomes, but careful follow-up and supportive care is recommended in order to prevent peri-implant MRONJ and IRS. Implant placement in high-dose patients must be strictly considered in a comprehensive multidisciplinary center.
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  • 文章类型: Practice Guideline
    目的:“2023年AHA/ACC/ACCP/ASPC/NLA/PCNA慢性冠心病患者管理指南”提供了更新并巩固了自“2012年ACCF/AHA/ACP/AATS/PCNA/SCAI/STS《稳定性缺血性心脏病患者诊断和管理指南》”和相应的“2014年ACCF/ASCNA《ACCF/ACP/ACATHA稳定性心脏病
    方法:从2021年9月至2022年5月进行了全面的文献检索。临床研究,系统评价和荟萃分析,以及对人类参与者进行的其他证据被确定为从MEDLINE(通过PubMed)以英文发表,EMBASE,Cochrane图书馆,医疗保健研究和质量机构,以及与本指南相关的其他选定数据库。
    本指南为慢性冠心病患者的管理提供了以证据为基础和以患者为中心的方法。考虑健康的社会决定因素,并纳入共同决策和基于团队的护理原则。相关主题包括治疗决策的一般方法,指南指导的管理和治疗,以减少症状和未来的心血管事件,关于慢性冠心病患者血运重建的决策,特殊人群的管理建议,患者随访和监测,证据缺口,以及未来需要研究的领域。如果适用,基于成本效益数据的可用性,还为临床医生提供了成本价值建议.以前发布的指南中的许多建议已经更新了新的证据,并且在发布的数据支持下创建了新的建议。
    The \"2023 AHA/ACC/ACCP/ASPC/NLA/PCNA Guideline for the Management of Patients With Chronic Coronary Disease\" provides an update to and consolidates new evidence since the \"2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease\" and the corresponding \"2014 ACC/AHA/AATS/PCNA/SCAI/STS Focused Update of the Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease.\"
    A comprehensive literature search was conducted from September 2021 to May 2022. Clinical studies, systematic reviews and meta-analyses, and other evidence conducted on human participants were identified that were published in English from MEDLINE (through PubMed), EMBASE, the Cochrane Library, Agency for Healthcare Research and Quality, and other selected databases relevant to this guideline.
    This guideline provides an evidenced-based and patient-centered approach to management of patients with chronic coronary disease, considering social determinants of health and incorporating the principles of shared decision-making and team-based care. Relevant topics include general approaches to treatment decisions, guideline-directed management and therapy to reduce symptoms and future cardiovascular events, decision-making pertaining to revascularization in patients with chronic coronary disease, recommendations for management in special populations, patient follow-up and monitoring, evidence gaps, and areas in need of future research. Where applicable, and based on availability of cost-effectiveness data, cost-value recommendations are also provided for clinicians. Many recommendations from previously published guidelines have been updated with new evidence, and new recommendations have been created when supported by published data.
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  • 文章类型: Journal Article
    目的“2023年AHA/ACC/ACCP/ASPC/NLA/PCNA慢性冠心病患者管理指南”提供了更新并巩固了自“2012年ACCF/AHA/ACP/AATS/PCNA/SCAI/STS稳定性缺血性心脏病患者诊断和管理指南”和相应的“2014年ACC/AHA/ASCATNA稳定性心脏病/Focus诊断指南”以来的新证据。方法2021年9月至2022年5月进行了全面的文献检索。临床研究,系统评价和荟萃分析,以及对人类参与者进行的其他证据被确定为从MEDLINE(通过PubMed)以英文发表,EMBASE,Cochrane图书馆,医疗保健研究和质量机构,以及与本指南相关的其他选定数据库。本指南为慢性冠心病患者的管理提供了基于证据和以患者为中心的方法。考虑健康的社会决定因素,并纳入共同决策和基于团队的护理原则。相关主题包括治疗决策的一般方法,指南指导的管理和治疗,以减少症状和未来的心血管事件,关于慢性冠心病患者血运重建的决策,特殊人群的管理建议,患者随访和监测,证据缺口,以及未来需要研究的领域。如果适用,基于成本效益数据的可用性,还为临床医生提供了成本价值建议.以前发布的指南中的许多建议已经更新了新的证据,并且在发布的数据支持下创建了新的建议。
    The \"2023 AHA/ACC/ACCP/ASPC/NLA/PCNA Guideline for the Management of Patients With Chronic Coronary Disease\" provides an update to and consolidates new evidence since the \"2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease\" and the corresponding \"2014 ACC/AHA/AATS/PCNA/SCAI/STS Focused Update of the Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease.\"
    A comprehensive literature search was conducted from September 2021 to May 2022. Clinical studies, systematic reviews and meta-analyses, and other evidence conducted on human participants were identified that were published in English from MEDLINE (through PubMed), EMBASE, the Cochrane Library, Agency for Healthcare Research and Quality, and other selected databases relevant to this guideline.
    This guideline provides an evidenced-based and patient-centered approach to management of patients with chronic coronary disease, considering social determinants of health and incorporating the principles of shared decision-making and team-based care. Relevant topics include general approaches to treatment decisions, guideline-directed management and therapy to reduce symptoms and future cardiovascular events, decision-making pertaining to revascularization in patients with chronic coronary disease, recommendations for management in special populations, patient follow-up and monitoring, evidence gaps, and areas in need of future research. Where applicable, and based on availability of cost-effectiveness data, cost-value recommendations are also provided for clinicians. Many recommendations from previously published guidelines have been updated with new evidence, and new recommendations have been created when supported by published data.
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  • 文章类型: Journal Article
    结论:为了加快文章的发表,AJHP在接受后尽快在线发布手稿。接受的手稿经过同行评审和复制编辑,但在技术格式化和作者打样之前在线发布。这些手稿不是记录的最终版本,将在以后替换为最终文章(按照AJHP样式格式化并由作者证明)。
    目的:基于固定剂量和体重指数(BMI)的依诺肝素方案对许多创伤患者的静脉血栓栓塞(VTE)预防不足。这项研究的目的是评估基于新的血容量(BV)的依诺肝素指南与基于BMI的历史指南在创伤患者中预防VTE的有效性。
    方法:这是一项在大型学术一级创伤中心完成的回顾性前/后研究。纳入了2019年10月至12月和2020年8月至10月收治的所有成人创伤患者,这些患者根据指南接受了预防性依诺肝素。BV剂量如下:BV为3至4.9L的患者每12小时接受依诺肝素30mg,那些BV为5至6.9L的人每12小时接受40毫克,BV≥7L的患者每12小时接受60mg。主要结果是在第一次稳态评估(0.2至0.5IU/mL)时,给药后达到目标抗因子Xa(抗Xa)水平的患者百分比。
    结果:共纳入241例患者(BMI组99例,BV组142例)。研究组的中位年龄为38岁和42岁,平均BMI为27.4对27.7kg/m2,平均BV为5.1对5.1L,分别。BMI组中共有63名患者(62.6%)达到目标抗Xa水平,而BV组中有115名患者(81%)(P=0.008)。在多元回归中,基于BV的指南是与达到目标抗Xa水平相关的唯一变量(调整后的比值比,2.02;P=0.01)。两组间临床相关出血和VTE发生率相似。
    结论:使用基于BV的给药指南的预防性依诺肝素给药显著增加了目标抗Xa水平的实现。
    Fixed-dose and body mass index (BMI)-based enoxaparin regimens provide inadequate venous thromboembolism (VTE) prophylaxis for many trauma patients. The purpose of this study was to evaluate the effectiveness of a novel blood volume (BV)-based enoxaparin guideline vs a historical BMI-based guideline for VTE prophylaxis in trauma patients.
    This was a retrospective pre/post study completed at a large academic level 1 trauma center. All adult trauma patients admitted from October through December 2019 and August through October 2020 who received prophylactic enoxaparin per guideline were included. The BV dosing was as follows: patients with a BV of 3 to 4.9 L received enoxaparin 30 mg every 12 hours, those with a BV of 5 to 6.9 L received 40 mg every 12 hours, and those with a BV of ≥7 L received 60 mg every 12 hours. The primary outcome was the percentage of patients who attained a target anti-factor Xa (anti-Xa) postdosing level at the first steady-state assessment (0.2 to 0.5 IU/mL).
    A total of 241 patients (99 for the BMI group and 142 for the BV group) were included. The study groups had a median age of 38 vs 42 years, a mean BMI of 27.4 vs 27.7 kg/m2, and a mean BV of 5.1 vs 5.1 L, respectively. A total of 63 patients (62.6%) in the BMI group attained target anti-Xa levels compared to 115 patients (81%) in the BV group (P = 0.008). In multivariate regression, the BV-based guideline was the only variable associated with attainment of target anti-Xa levels (adjusted odds ratio, 2.02; P = 0.01). Clinically relevant bleeding and VTE rates were similar between the groups.
    Dosing prophylactic enoxaparin using a BV-based dosing guideline significantly increased attainment of target anti-Xa levels.
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  • 文章类型: English Abstract
    Conventional synthetic (cs) and targeted synthetic (ts) disease-modifying antirheumatic drugs (DMARD) have potential interactions with a multitude of drugs. Furthermore, they sometimes have a lower therapeutic index, particularly in cases of limited organ functions. The aim of this work was to establish evidence-based recommendations on the therapeutic use of DMARDs in the context of drug interactions and dosage recommendations. A systematic literature search was carried out on the issue of drug interactions and dosages in cases of patients with limited kidney function and higher age and suffering from rheumatoid arthritis. A total of 2756 scientific publications were screened and 154 selected of which 68 were scrutinized in detail. Furthermore, the respective specialist subject information was also analyzed. A multitude of possible interactions of synthetic DMARDs with different drugs were detected, which were then assessed with respect to the clinical significance and consequences. A consensus process led to making recommendations with which the interactions were classified: A: dangerous combination, B: avoid combination (if possible, pausing DMARD treatment), C: possible combination requiring increased monitoring and potential adjustments in dosage and D: pharmacological interaction without relevance in DMARD standard doses. Apart from that dosage recommendations were established for each csDMARD and tsDMARD depending on kidney function and age. There are 3 primary recommendations and 11 core recommendations on interactions and dosages of csDMARDs and tsDMARDs meant as a practical help for therapeutic decision making and to improve safety in the treatment of rheumatoid arthritis.
    UNASSIGNED: Konventionelle synthetische („conventional synthetic“ [cs]) und gezielte synthetische („targeted synthetic“ [ts]) DMARDs haben potenzielle Wechselwirkungen mit einer Vielzahl von Medikamenten. Darüber hinaus haben sie insbesondere bei eingeschränkten Organfunktionen teilweise eine geringe therapeutische Breite. Ziel der Arbeit war eine systematische Erarbeitung von evidenzbasierten Empfehlungen zur Therapie mit DMARDs im Kontext von Arzneimittelinteraktionen und Dosierungsempfehlungen. Es wurde eine systematische Literaturrecherche zur Frage nach Wechselwirkungen sowie Dosierungen bei eingeschränkter Nierenfunktion und höherem Lebensalter bei rheumatoider Arthritis durchgeführt. Insgesamt wurden 2756 wissenschaftliche Publikationen gescreent und 154 ausgewählt, wobei 68 Publikationen in eine detaillierte Analyse eingingen. Darüber hinaus wurden die Informationen der jeweiligen Fachinformationen analysiert. Es fand sich eine Vielzahl von möglichen Wechselwirkungen von synthetischen DMARDs mit verschiedenen Medikamenten, welche bezüglich klinischer Bedeutung und Konsequenz bewertet wurden. In einem Konsensprozess wurden Empfehlungen erarbeitet, wobei eine Graduierung der Wechselwirkungen erfolgte: A: gefährliche Kombination, B: Kombination meiden (wenn möglich DMARD-Pause), C: mögliche Kombination mit erhöhtem Überwachungsbedarf und evtl. Dosisanpassung, D: pharmakologische Interaktion ohne Relevanz in Standarddosierungen des DMARD. Es wurden darüber hinaus Dosierungsempfehlungen nach Nierenfunktion und Alter für jedes cs- und tsDMARD erarbeitet. Drei übergeordnete Empfehlungen und 11 Kernempfehlungen zu Wechselwirkungen und Dosierung von cs- und tsDMARDs sollen praktische Hilfestellung für therapeutische Entscheidungen geben und die Sicherheit der Therapie der rheumatoiden Arthritis verbessern.
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  • 文章类型: Journal Article
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  • 文章类型: Journal Article
    低密度脂蛋白胆固醇(LDL-C)已被认为是预防和治疗动脉粥样硬化性心血管疾病(ASCVD)的主要目标。然而,即使LDL-C达到目标水平,部分患者仍存在残余心血管风险.新的证据表明,甘油三酯(TG)水平升高或富含甘油三酯的脂蛋白(TRL)胆固醇(TRL-C)是残余心血管风险的重要组成部分之一。Omega-3脂肪酸已被证明是降低TG的有效药物之一。然而,在大型随机临床试验中,其降低ASCVD风险的疗效不一致.关于omega-3脂肪酸在心血管疾病(包括心力衰竭)中的应用,专家之间缺乏共识。心律失常,心肌病,高血压,突然死亡。因此,目前的共识将从多个方面全面、科学地呈现关于omega-3脂肪酸的详细知识,为omega-3脂肪酸在中国人群中的应用管理提供参考。
    Low-density lipoprotein cholesterol (LDL-C) has been considered as the primary target for the prevention and treatment of atherosclerotic cardiovascular disease (ASCVD). However, there are still residual cardiovascular risks in some patients even if LDL-C achieves the target level. Emerging evidence suggestes that elevated triglyceride (TG) level or triglyceride-rich lipoprotein (TRL) cholesterol (TRL-C) is one of the important components of the residual cardiovascular risks. Omega-3 fatty acids have been shown to be one of the effective drugs for reducing TG. However, its efficacy in reducing the risk of ASCVD is inconsistent in large randomized clinical trials. There is lack of consensus among Experts regarding the application of omega-3 fatty acids in cardiovascular diseases including heart failure, arrhythmia, cardiomyopathy, hypertension, and sudden death. Hence, the current consensus will comprehensively and scientifically present the detailed knowledge about the omega-3 fatty acids from a variety of aspects to provide a reference for its management of omega-3 fatty acids application in the Chinese population.
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