Aprocitentan

第36届长城心脏病学大会暨亚洲心脏大会2025期间，“难治性高血压与肾动脉去神经论坛”专场成功举办。论坛分“难治性高血压”与“肾动脉去神经术”上下两节，分别由新疆维吾尔自治区人民医院李南方教授、华中科技大学同济医学院附属协和医院汪朝晖教授、江苏省人民医院孙伟教授，以及中国医学科学院阜外医院吴海英教授、青岛市市立医院贾楠教授、大连医科大学附属第一医院张英教授等国内高血压领域知名专家联袂主持。与会专家围绕难治性高血压的管理策略、药物新靶点以及肾动脉去神经术（RDN）的前沿进展与临床应用展开了系统性、多维度的深入探讨。 牟建军教授：影响血压难以控制的因素与对策 西安交通大学第一附属医院的牟建军教授首先明确指出，难治性高血压是一个“管理概念”而非“疾病诊断概念”，许多难以控制的血压实则源于管理不当。他从医生、患者和卫生体系三个维度剖析了影响因素。医生层面，必须进行规范化管理，包括积极排查继发性高血压、干预影响血压的药物或疼痛等因素、提供个体化且可量化的生活方式指导，以及制定合理的个体化药物方案。他强调，在未进行充分的药物及管理优化前，不应草率转向RDN治疗。患者层面，依从性是核心，医生需通过充分的医患沟通、科普教育以及推广单片复方制剂（SPC）来提高患者的长期治疗依从性。 林金秀教授：难治性高血压药物治疗新进展 福建医科大学附属第一医院的林金秀教授系统梳理了难治性高血压的药物治疗新进展。他指出，在传统“三联”药物（RASi+CCB+利尿剂）基础上，第四种药物的选择正迎来革新。除了基于PATHWAY-2研究首选的盐皮质激素受体拮抗剂（MRA），三大新靶点药物展现出巨大潜力：一是醛固酮合成酶抑制剂（ASI），如Baxdrostat，在Bax HTN研究中展现了强大的降压效果，尤其是对夜间血压的控制；二是双重内皮素受体拮抗剂（DERA），如Aprocitentan，起效迅速；三是靶向肝脏血管紧张素原的siRNA药物，如Zilebesiran，可实现半年一针的长效控制，但需联合利尿剂或CCB。他强调，第四线药物的选择应基于患者的肾素水平、心率等特征进行精准个体化。 冯颖青教授：内皮素ETA/ETB受体拮抗剂在难治性高血压中的应用 广东省人民医院的冯颖青教授深入解析了内皮素受体拮抗剂的作用机制。她指出，内皮素-1（ET-1）是强效缩血管物质，其通过ETA受体介导血管收缩、增殖和炎症等“有害”效应，而通过ETB受体介导血管舒张和利钠等“有益”效应。早期拮抗剂因肝毒性及水钠潴留等副作用失败。新一代双重拮抗剂Aprocitentan在三期PRECISION研究中，证实了其在已接受三药治疗的难治性高血压患者中，仍能显著额外降低血压，且半衰期长达44小时，不良反应主要为可控的水肿，为临床提供了新的治疗选择。 刘靖教授：醛固酮靶向治疗，难治性高血压的新选择 北京大学人民医院的刘靖教授聚焦于醛固酮靶向治疗。她指出，传统MRA（如螺内酯）虽有效，但因竞争性阻断性激素受体等导致不良反应，限制了其在高血压治疗中的足量应用。而非甾体MRA（如非奈利酮）尚未获高血压适应症。真正的突破在于“上游”抑制，即高选择性醛固酮合成酶抑制剂（ASI），如Baxdrostat和Lorundrostat。此类药物特异性抑制CYP11B2，几乎不影响皮质醇合成，从而规避了传统MRA的副作用。Bax-HTN和ADVANCE-HTN研究均证实，ASI在未控制及难治性高血压患者中能带来显著的额外血压降幅（约8-10mmHg），为难治性高血压管理提供了极具前景的新策略。 周玉杰教授：难治性高血压的器械治疗新进展 首都医科大学附属北京安贞医院的周玉杰教授生动展示了器械治疗（RDN）的进展。他回顾了从外科交感神经切除术到现代RDN的历史。RDN的原理在于利用射频能量（约60℃）选择性毁损肾动脉外膜4mm内的交感神经（45℃即失活），而不损伤血管内皮（65℃才受损）。他指出HTN-3试验的失败源于术者经验不足及消融策略缺陷。现代RDN技术强调使用多极导管（如螺旋、网篮）进行“应消尽消”的彻底消融，包括分支及副肾动脉。RDN可提供全天候、持久（10年随访数据）且独立于药物的降压效果，尤其适用于交感活性高、合并房颤、心衰或依从性差的患者。 蒋雄京教授：RDN上市后研究，有哪些迫切需要回答的问题？ 中国医学科学院阜外医院的蒋雄京教授高屋建瓴地指出了RDN上市后面临的核心挑战。他强调，现有RCT研究显示RDN的平均降压幅度有限（对比假手术约4.4mmHg），且存在25-33%的无应答率。因此，上市后研究迫切需要回答：如何筛选出真正的“应答者”？（目前除高基线血压外尚无明确预测指标）；如何确立术中消融的“终点”？（即如何判断消融已足够）。他呼吁开展大规模真实世界研究，以验证国产设备的长期安全性（尤其是肾动脉变化）、有效性，并积极探索RDN在CKD、心衰、房颤及备孕女性等扩展人群中的应用价值。 许建忠教授：RDN基本原理及多领域应用 上海交通大学医学院附属瑞金医院的许建忠教授深入阐述了RDN的双重机制，即同时阻断传出神经（减少肾素、利钠、扩血管）和传入神经（即刻降压）。他强调，RDN不仅是局部去神经，更是重塑了肾脏调节血压的核心功能。他指出，所有RDN试验的治疗组血压均下降，阴性结果源于假手术组的高反应。在多领域应用方面，RDN在心衰患者中显示出独立于降压的（可能源于神经内分泌改善）心功能获益；在CKD患者中（尤其是eGFR 20-40的患者）展现出安全降压的潜力；在房颤患者中，RDN联合PVI（肺静脉隔离）可能减少房颤复发，但需厘清血压下降的混杂效应。 黄晶教授：RDN治疗高血压新靶点探索 重庆医科大学附属第二医院的黄晶教授分享了RDN新靶点的探索。他指出，当前经血管路径的RDN存在局限。新方向包括：1.靶向主肾神经节，可能效应更强但技术难度大；2.利用体外聚焦超声（FUS）等无创能量，但面临深度控制难题，其团队正探索更浅的“经肾门”超声消融路径；3.靶向肾盂传入神经，通过输尿管导管或体外超声阻断压力感知信号，初步显示良好降压效果；4.腹腔镜下肾动脉外周360°消融；5.联合肝动脉去神经，可能通过更广泛的内脏神经调节产生更强降压效应。这些探索旨在寻求更彻底、更精准的去神经策略。 卜培莉教授：RDN适宜人群筛选和研究进展 山东大学齐鲁医院的卜培莉教授强调了RDN成功实施的关键在于严格的患者筛选。她详细解读了2025年中国共识中的禁忌症，包括严重的肾动脉结构异常（狭窄>50%、动脉瘤等）、eGFR<40（临床研究外）、6个月内急性心脑血管事件、妊娠及<18岁等。适应症则包括真正的难治性高血压（经ABPM确认）以及因药物不耐受或依从性极差导致控制不佳的患者。她指出，RDN的推广极大推动了高血压学科的规范化管理，术前必须完成对继发性高血压的全面排查和解剖可行性评估。她总结，RDN手术是规范化管理的“开始”而非“终点”，必须结合长期的随访管理和生活方式干预。 结语 本次“难治性高血压与肾动脉去神经论坛”以前瞻性的视野，系统性地呈现了破解高血压“难治”困局的多维策略。从管理理念的革新、个体化药物方案的优化，到靶向醛固酮合成酶、内皮素受体等新药研发的重大突破，再到肾动脉去神经术（RDN）的临床挑战、多领域应用、新靶点探索及严格的患者筛选，论坛全景式地展示了高血压治疗正从传统模式向量身定制的精准医学时代迈进。药物创新与器械治疗的齐头并进，正为攻克难治性高血压这一临床难题提供日益丰富的“组合拳”。 GW-ICC/AHS 2025 点击阅读原文 关注最新资讯

New analysis confirms reductions in blood pressure and albuminuria by aprocitentan in patients with true resistant hypertension and high cardiovascular risk – including chronic kidney disease Allschwil, Switzerland – November 05, 2025Idorsia Ltd (SIX: IDIA) shares that new analysis of the landmark Phase 3 PRECISION study of aprocitentan, Idorsia’s endothelin receptor antagonist, will be presented at the American Society of Nephrology (ASN) Kidney Week 2025, taking place in Houston, TX, November 5–9, 2025. A poster presentation entitled “Is Aprocitentan's Effect on Albuminuria Merely Due to Lowered BP? Subgroup Analysis of the PRECISION Trial” will be held in the Hypertension and CVD: Clinical – 1 session on November 6, at 10:00-12:00 CT (Abstract). The poster highlights that aprocitentan, in addition to at least three antihypertensives, substantially reduced systolic blood pressure and Urine Albumin-to-Creatinine Ratio (UACR) versus placebo across all subgroups with renal impairment and resistant hypertension. The correlation analysis shows that the highly significant reductions in blood pressure with aprocitentan do not solely explain the observed reductions in UACR, suggesting that additional mechanisms are involved in aprocitentan’s renal-protective effect, such as a decrease in glomerular permeability, post-glomerular vasodilation or functional tubular changes. In addition, Idorsia will be present at The American Heart Association (AHA) Scientific Sessions 2025, taking place in New Orleans, LA, November 7–10, 2025, with a sponsored educational symposium entitled ‘The Next Era in the Treatment of Hypertension’. The symposium will take place in Learning Studio 1 on November 9, at 9:30am - 10:15am CT. Dr Michael Bloch, Associate Professor, Department of Internal Medicine at University of Nevada School of Medicine and Medical Director of Vascular Medicine and Anticoagulation Services at the Renown Medical Center Institute for Heart and Vascular Health, will present data from the PRECISION trial and discuss the use of aprocitentan in clinical practice. Notes to the editor About aprocitentanAprocitentan is Idorsia’s once-daily, orally active, dual endothelin receptor antagonist, which inhibits the binding of ET-1 to ETA and ETB receptors. Aprocitentan is approved as TRYVIO® in the US for the treatment of systemic hypertension in combination with other antihypertensives and has been commercially available since October 2024. For more information see the Full Prescribing Information including BOXED Warning (PI and Medication Guide). TRYVIO is now included in the American College of Cardiology’s (ACC) and the American Heart Association’s (AHA) new comprehensive clinical practice guidelines for the management of high blood pressure. Aprocitentan is approved as JERAYGO® for the treatment of resistant hypertension in combination with other antihypertensives in the European Union, the UK, and Switzerland, and a marketing authorization application is under review in Canada. About IdorsiaThe purpose of Idorsia is to challenge accepted medical paradigms, answering the questions that matter most. To achieve this, we will discover, develop, and commercialize transformative medicines – either with in-house capabilities or together with partners – and evolve Idorsia into a leading biopharmaceutical company, with a strong scientific core. Headquartered near Basel, Switzerland – a European biotech hub – Idorsia has a highly experienced team of dedicated professionals, covering all disciplines from bench to bedside; QUVIVIQ™ (daridorexant), a different kind of insomnia treatment with the potential to revolutionize this mounting public health concern; strong partners to maximize the value of our portfolio; a promising in-house development pipeline; and a specialized drug discovery engine focused on small-molecule drugs that can change the treatment paradigm for many patients. Idorsia is listed on the SIX Swiss Exchange (ticker symbol: IDIA). For further information, please contact:Investor & Media RelationsIdorsia Pharmaceuticals Ltd, Hegenheimermattweg 91, CH-4123 Allschwil+41 58 844 10 10investor.relations@idorsia.com – media.relations@idorsia.com – www.idorsia.com The above information contains certain "forward-looking statements", relating to the company's business, which can be identified by the use of forward-looking terminology such as “intend”, "estimates", "believes", "expects", "may", "are expected to", "will", "will continue", "should", "would be", "seeks", "pending" or "anticipates" or similar expressions, or by discussions of strategy, plans or intentions. Such statements include descriptions of the company's investment and research and development programs, business development activities and anticipated expenditures in connection therewith, descriptions of new products expected to be introduced by the company and anticipated customer demand for such products and products in the company's existing portfolio. Such statements reflect the current views of the company with respect to future events and are subject to certain risks, uncertainties and assumptions. Many factors could cause the actual results, performance or achievements of the company to be materially different from any future results, performances or achievements that may be expressed or implied by such forward-looking statements. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those described herein as anticipated, believed, estimated or expected. Attachment Press Release PDF