Telmisartan

GMRx2 significantly reduced the risk of recurrent stroke when added to standard of care compared to placeboTrial results were presented during a plenary session of the World Stroke Congress 2025 in Barcelona London, UK, Boston, MA, 23 October 2025 – George Medicines, a late-stage biopharmaceutical company focused on addressing significant unmet needs in cardiometabolic disease, today announced that positive results from the investigator-initiated TRIDENT trial have been shared at the World Stroke Congress in Barcelona. The study met the primary endpoint, with GMRx2 (a single pill low-dose combination therapy of telmisartan, amlodipine and indapamide) demonstrating a statistically significant and clinically meaningful reduction of recurrent stroke compared to matching placebo. The TRIDENT trial was conducted in patients with a history of acute stroke due to intracerebral hemorrhage (ICH) on standard of care treatment. The trial was led by The George Institute for Global Health and funded by the National Health and Medical Research Council (NHMRC) Australia and the Brazilian Ministry of Health, with study medication provided by George Medicines. The safety profile of GMRx2 in the TRIDENT trial was generally consistent with the well-established safety profile of the medicine, and its individual components. Mark Mallon, Chief Executive Officer of George Medicines, said: “The TRIDENT trial represents an important step towards understanding how enhanced blood pressure management has the potential to reduce the risk of recurrent stroke after an intracerebral hemorrhage, the most severe type of stroke. Reducing the global burden of cardiovascular disease lies at the heart of our mission and we are proud that our single pill triple combination therapy demonstrated efficacy in this study.” Acute ICH accounts for at least 10 per cent of the 20 million new strokes in the world each year. ICH survivors are at high risk of recurrent stroke and other serious cardiovascular events. Numerous studies have indicated a benefit of stroke survivors reducing their risk of recurrent stroke through taking blood pressure-lowering medications. However, studies have also shown that many stroke survivors are either not receiving any blood pressure-lowering medication, or they are receiving inadequate control. TRIDENT is the first stroke outcomes trial with a low-dose single pill triple combination therapy for blood pressure treatment in adults with a history of ICH on top of standard of care. Full results from the trial will be submitted for publication in a peer-reviewed journal. Ends About TRIDENT TRIDENT was a multicenter, international, double-blind, placebo-controlled, parallel-group, randomized controlled trial in patients with a history of ICH designed to evaluate the effect of GMRx2 (telmisartan 20 mg/ amlodipine 2.5mg/ indapamide 1.25mg), compared with placebo, given once daily in addition to standard of care. The primary outcome was the time to first occurrence of recurrent stroke. About GMRx2GMRx2 is a combination tablet of telmisartan, an angiotensin II receptor blocker, amlodipine, a dihydropyridine calcium channel blocker and indapamide, a thiazide-like diuretic, developed in three dosage forms – 10/1.25/0.625 mg; 20/2.5/1.25 mg and 40/5/2.5 mg – for the treatment of hypertension. Its development is backed by a comprehensive clinical program, including two pivotal Phase III studies in hypertension, published in 2024 in the Journal of the American College of Cardiology and The Lancet. In these trials the triple combination demonstrated significantly reduced blood pressure and improved blood pressure control rates, when compared against dual therapy and against placebo. In both trials, tolerability was good, with no increase in withdrawal from treatment due to adverse events. GMRx2 was also investigated in the Nigerian VERONICA trial, which compared the triple combination with standard of care and reported better blood pressure lowering among those receiving GMRx2, with good tolerability compared to the standard of care protocol. About George Medicines George Medicines is a late-stage biopharmaceutical company addressing significant unmet need in the treatment of cardiometabolic diseases with innovative single-pill combinations of existing treatments, designed for a balance of efficacy and safety, with the potential to improve patient adherence. Multi-mechanism, single-pill combinations offer the potential to bring significant improvements in clinical outcomes with cardiometabolic disorders, including hypertension, which remain among the leading causes of premature death and disability worldwide. George Medicines is an independent spin-out company from The George Institute for Global Health, one of the world’s leading medical research institutes with a focus on addressing global health inequity. The Company is backed by George Health, the commercial arm of The George Institute, and Brandon Capital, Australia’s leading life sciences venture capital firm. For more information, please visit www.george-medicines.com. Safe Harbor StatementThis press release contains “forward-looking statements,” including statements relating to George Medicines’ financial position and long-term outlook on its business, including the commercialization of its approved products and the clinical development of, regulatory filings for, and potential therapeutic and commercial potential. In addition, this press release also contains forward-looking statements relating to George Medicines’ growth and future operating results, discovery, development and commercialization of products, strategic alliances and intellectual property, as well as other matters that are not historical facts or information. All forward-looking statements are based on management’s current assumptions and expectations and involve risks, uncertainties and other important factors, specifically including George Medicines’ ability to successfully commercialize its approved products, successfully conduct preclinical and clinical development and obtain necessary regulatory approvals of drug candidates. Media contacts ICR Healthcare David Daley, Lindsey Neville, Tom Daniel georgemedicines@icrhealthcare.com; Tel: +44 (0) 203 709 5700

点击“蓝字”关注我们 编者按：原发性醛固酮增多症（PA，简称“原醛症”）是继发性高血压的常见病因之一，其心脑血管和肾脏损害风险远高于原发性高血压。然而临床实践中，PA的诊断率低于其实际患病率，不少患者被漏诊或误诊。在10月10~12日召开的京医论坛-第十四届北京老年内分泌研讨会上，郑州大学第一附属医院秦贵军教授深度剖析了PA诊断的核心难点，并结合典型病例加以阐释。本文跟随秦贵军教授的思路，一起抽丝剥茧，揭开PA诊断中的层层迷雾。 秦贵军 教授 郑州大学第一附属医院 主任医师  二级教授  医学博士  博士生导师 郑州大学第一附属医院内分泌医学部主任 郑州大学特聘教授 郑州大学内科学系主任 享受国务院特殊津贴、中原学者等荣誉 中华医学会内分泌学分会常委性腺学组组长 中华医学会糖尿病学分会副主任委员 中国医师协会内分泌代谢科医师分会常委 河南省医学会糖尿病学分会主任委员 主持国家自然科学基金7项 在Nature Metabolism等杂志发表SCI论文100余篇 获河南省科学技术进步奖一等奖、二等奖5项 一、PA患病率高且隐匿，筛查很有必要 原发性醛固酮增多症（primary aldosteronism，PA）在高血压人群中的患病率远超以往认知，被称作“被忽视的继发性高血压”。研究显示，在初级医疗机构就诊的高血压患者中，PA患病率约为5.9%；在难治性高血压患者中，这一比例可高达15%～20%；而当高血压患者合并低血钾时，PA的患病率会进一步升高至28.1%[1,2]。 更需要注意的是，即使在血压正常的人群中，也存在一定比例的PA“隐形”患者[3]。这意味着相当一部分PA患者在早期可能血压并不高，却已存在醛固酮的异常分泌。另有研究显示，PA患者的心血管事件风险几乎是普通人群的两倍，且与更高的死亡率、房颤和糖尿病风险相关。 鉴于PA的高患病率与隐匿性，对特定人群进行筛查非常必要——通过及时发现可疑病例，再经确诊试验和分型诊断，可让更多PA患者获得早期诊断与规范治疗。 二、PA诊断与治疗中的争议与挑战 尽管PA早诊早治至关重要，但诊疗中仍有诸多争议与挑战：血压不高一定不是PA？PA筛查是否必须停药？肾素不低，是否可以排除PA？AVS提示单侧优势，术后一定能治愈吗？ 01 血压不高一定不是PA？ 案例回顾：从“正常”到确诊的四年 患者为26岁女性，体检发现左侧肾上腺腺瘤，但血压（120/75 mmHg）和血钾均正常。入院检查显示卧位醛固酮98.3 pg/ml，肾素0.25 ng/(ml·h)，血浆醛固酮与肾素活性的比值（ARR）约39.3；立位醛固酮124.6 pg/ml，肾素0.49 ng/(ml·h)，ARR约25.4。筛查发现，其立位ARR虽未超过30的筛查阈值，但肾素水平已被显著抑制[0.25 ng/（ml·h）]，提示存在非肾素依赖性的醛固酮自主分泌。生理盐水输注试验后醛固酮仍>100 pg/ml，卡托普利抑制试验2小时醛固酮>110 pg/ml，均未被抑制。综合考虑，临床高度怀疑PA。 当时，患者因无高血压症状拒绝治疗。4年后，她因“头胀、乏力1月余”再次入院。此时，血压已高达165/112 mmHg，血钾降至3.2 mmol/L，立位醛固酮223.56 pg/ml，肾素0.24 ng/(ml·h)，立位ARR高达93.15，显著高于阈值。遂再次完善盐水负荷抑制试验和卡托普利抑制试验，均未被抑制，原醛诊断明确。进一步完善肾上腺静脉采血（AVS）提示左侧肾上腺醛固酮分泌优势，遂行左肾上腺腺瘤切除。术后患者血压、血钾恢复正常，实现临床治愈。 分析与启示：认识“亚临床PA症” 这个病例完美诠释了PA是一个持续进展的疾病谱——从最初的醛固酮自主分泌，到出现生化异常（亚临床PA），再到最终发展为显性高血压和低血钾，这是一个连续的过程（图1）。该患者初诊时，虽无高血压，但“被抑制的肾素”已是早期PA的有力线索。 图1. PA是持续进展的综合征 尽管传统观点认为高血压、醛固酮＞150 pg/ml和ARR>30是PA筛查的三要素，但任何一个疾病都是在其病理机制下逐步发生发展的过程，诊断可以靠切点，但是临床思维不应该被切点所割裂。PA的本质是肾素非依赖性的醛固酮不适当分泌增多，当患者在肾素被抑制的前提下，醛固酮仍不足够低，即使ARR小于切点，我们也不可直接排除PA可能。对于存在高危因素（如肾上腺意外瘤、PA家族史）的个体，即使血压正常，也应进行PA筛查。筛查时，不应只简单关注ARR比值，而是要理解原醛的本质是“非肾素依赖性的醛固酮自主分泌”。对于这类“亚临床PA”患者，即便暂时不干预，也必须进行长期随访监测。 02 PA筛查是否必须停药？ 案例回顾：正在服药的高血压患者进行PA筛查 一位46岁男性，高血压8年，长期服用硝苯地平控释片和替米沙坦，但血压控制仍不佳（145/95 mmHg）。筛查PA时，分别于停药前、停药过洗脱期后进行了2次卧立位试验。 停药前卧立位试验结果显示，卧位醛固酮136.53 pg/ml，肾素0.31 ng/(ml·h)，ARR约44.04；立位醛固酮178.65 pg/ml，肾素0.56 ng/(ml·h)，ARR约31.90。停药过洗脱期后卧立位试验结果显示，卧位醛固酮168.22 pg/ml，肾素0.13 ng/(ml·h)，ARR约129.4；立位醛固酮201.83 pg/ml，肾素0.18 ng/(ml·h)，ARR约112.12。生理盐水输注试验、卡托普利抑制试验也支持PA诊断。 分析与启示：精准解读药物的“干扰项” PA筛查的目的是发现可疑患者，而非精准诊断，是通过必要的检查给临床判断提供可分析的依据。那么，理想状态下，筛查前应停用干扰药物至少2~4周。但对于血压较高的患者，停药可能带来风险和患者的脱漏。因此，更关键的是理解不同药物对ARR的影响机制，从而进行审慎判读（图2）。 图2. 服用降压药物患者接受PA症筛查的建议流程[4] 导致ARR假阴性（漏诊风险）的药物：排钾利尿剂、血管紧张素转换酶抑制剂（ACEI）、血管紧张素受体拮抗剂（ARB）和二氢吡啶类钙通道阻滞剂（CCB）等会升高肾素水平或降低醛固酮水平，从而拉低ARR值。如果患者在服用这些药物（尤其是ACEI/ARB）期间，ARR值依然显著升高，那么PA的可能性极高，结果反而更具说服力。 导致ARR假阳性（误诊风险）的药物：β受体阻滞剂、中枢α2受体激动剂、非甾体抗炎药等通过抑制肾素来抬高ARR值。如果患者在服用这类药物时ARR值处于临界升高状态，需高度怀疑假阳性的可能，最好能在换用影响较小的药物（如α受体阻滞剂、维拉帕米缓释片）后复查。 PA筛查可以不停药，但确诊试验及分型诊断（AVS）前必须停药并洗脱，以避免误诊！ 03 肾素不低，是否可以排除PA？ 案例回顾：肾素未被抑制的高血压患者 患者女性，23岁，1年前发现血压升高，最高血压180/112 mmHg，既往服用“硝苯地平控释片30 mg qd，缬沙坦80 mg qd”，血压控制在151/98 mmHg左右。随机位试验结果显示立位醛固酮238.70 pg/ml，肾素3.5 ng/(ml·h)，ARR约6.82，同步血钾：3.10 mmol/L。调整降压药物，2周后复查结果显示卧位醛固酮207.50 pg/ml，肾素2.7 ng/(ml·h)，ARR约7.69；立位醛固酮286.30 pg/ml，肾素4.1 ng/(ml·h)，ARR约6.98。 这位年轻患者药物已洗脱、血钾恢复正常，血儿茶酚胺、肾功、血沉、类风湿及结缔组织病检查均未见异常。需注意的是，焦虑及抑郁量表提示其重度焦虑及轻度抑郁。盐水负荷后，肾素被抑制，为0.21 ng/(ml·h)；但醛固酮仍＞100 pg/ml，提示存在肾素非依赖性的醛固酮分泌增多。完善AVS提示左侧肾上腺醛固酮分泌优势，遂行左肾上腺腺瘤切除，术后实现临床治愈。 分析与启示：结合临床综合判断 肾素受抑制是PA的典型表现，但肾素“不低”并不一定排除PA。在评估肾素水平时，应结合临床综合判断。如果患者有典型的PA临床表现（如难治性高血压），应排除肾素升高的因素，如肾动脉狭窄、副肾动脉或精神心理因素等。 04 AVS提示单侧优势，术后一定能治愈吗？ 对于筛查和确诊为PA的患者，明确病因分型对制定治疗策略至关重要。AVS是区分单侧醛固酮瘤（APA）与双侧肾上腺增生（IHA）的金标准，但其结果解读需要格外谨慎。 在AVS检查中，促肾上腺皮质激素（ACTH）的作用机制值得关注。ACTH受体在醛固酮生成性腺瘤或微结节中呈高表达，而在正常肾上腺皮质组织中表达水平较低。当患者存在双侧醛固酮生成性微结节（细胞簇）时，在基础状态下一侧醛固酮表达可能相对弱势，但在ACTH刺激下，该侧肾上腺的微结节功能会被进一步激活，从而失去原有的分泌优势。 因此，在AVS检查中加入ACTH兴奋试验有助于提高分型诊断的准确性，为临床治疗决策提供更可靠的依据。 三、结语 PA的诊断过程既复杂又严谨，要求临床医生全面考量多种因素。即便血压正常，也不应轻易排除PA，早期筛查对发现隐匿病例至关重要；药物干扰可能影响筛查结果，需结合患者具体情况权衡停药或药物调整；肾素水平正常不能作为排除PA的依据，应排除导致肾素升高的潜在因素；AVS虽为分型金标准，但结果解读需格外谨慎，而ACTH兴奋下的AVS可显著提升分型准确性。总之，PA的早期诊断和治疗对改善患者预后至关重要，然而在实际工作中，我们必须直面这些诊断挑战，避免因认知不足而引发漏诊或误诊。 参考文献： 1.Stella D, et al. Lancet, 2008,371(9628):1921-1926. 2.Burrello J, et al. Hypertension 2020;75:1025-1033 3.Xu Z, et al. JACC 2020; 75:1913-1922. 4.中华医学会内分泌学分会. 中华内分泌代谢杂志，2025，41(01):12-24. 声明：本文仅供医疗卫生专业人士了解最新医药资讯参考使用，不代表本平台观点。该等信息不能以任何方式取代专业的医疗指导，也不应被视为诊疗建议，如果该信息被用于资讯以外的目的，本站及作者不承担相关责任。 最新《国际糖尿病》读者专属微信交流群建好了，快快加入吧！扫描左边《国际糖尿病》小助手二维码（微信号：guojitnb），回复“国际糖尿病读者”，ta会尽快拉您入群滴！ （来源：《国际糖尿病》编辑部） 版权声明 版权属《国际糖尿病》所有。欢迎个人转发分享。其他任何媒体、网站未经授权，禁止转载。