Amlodipine/Telmisartan/Indapamide

如何持续有效降压？这是全球范围内临床医生和高血压患者都很关注的问题。近期相关高血压指南建议：对于大多数高血压患者的初始治疗，可采用指南推荐的两种降压药组合治疗策略，以更好地控制血压，提高患者依从性，减少治疗惰性。指南同时建议早期使用三联降压药开始治疗，最好是单片复方制剂（SPC）。当前，三联单片复方制剂仅适用于复方片剂所包含的所有三种药物，或是使用其中两种药物但血压控制不佳的患者。 近日，《柳叶刀》（The Lancet）发表由替米沙坦、氨氯地平、吲达帕胺构成的单片复方制剂GMRx 2在成年高血压患者中的应用研究数据，结果显示相比于以上三种药物任意两两组合，GMRx 2降压效果更好，安全可耐受。GMRx 2为高血压的临床管理提供了一种新的治疗选择，有望在临床实践中为高血压患者带来实质性的降压疗效。 截图来源：The Lancet 这是一项国际、随机、双盲、活性对照、平行组试验。研究纳入全球多个国家的83家临床医学中心年龄18岁以上高血压患者1385例。若患者既往未使用降压药，则诊室收缩压需在140~179 mmHg；若使用1种降压药，则诊室收缩压需在130~170 mmHg；若使用2种降压药，则诊室收缩压需在120~160 mmHg；若使用3种降压药，则诊室收缩压需在110~150 mmHg。 纳入的患者需先接受为期4周的单盲、活性药物导入期，期间接受一半剂量的GMRx 2。导入期平均诊室血压为142/85 mmHg。导入期结束，若患者家庭收缩压在110~154 mmHg，对治疗耐受且能够遵守家庭血压测量计划，则将参与到下一阶段随机分组。随机化时平均诊室血压为133/81 mmHg、平均家庭血压为129/78 mmHg。研究人员将符合要求的患者以2：1：1：1的比例随机分配接受下列4种治疗方案，持续治疗6周： 继续接受一半剂量的GMRx 2（551例）； 替米沙坦20 mg+氨氯地平2.5 mg（282例）； 替米沙坦20 mg+吲达帕胺1.25 mg（276例）； 氨氯地平2.5 mg+吲达帕胺1.25 mg（276例）。 治疗6周时，除非有明确的临床禁忌证，否则所有组的用药剂量翻倍。整个治疗周期为12周。 研究结果显示，治疗第12周时，GMRx 2组家庭和诊室平均收缩压/舒张压降幅均高于其他三种降压药两两组合，其中： 相比于替米沙坦+吲达帕胺组，GMRx 2组家庭收缩压/舒张压多降低2.5/2.1 mmHg（P＜0.0001）、诊室收缩压/舒张压多降低4.3/3.5 mmHg（P＜0.0001）； 相比于替米沙坦+氨氯地平组，GMRx 2组家庭收缩压/舒张压多降低5.4/3.4 mmHg（P＜0.0001）、诊室收缩压/舒张压多降低5.6/3.7 mmHg（P＜0.0001）； 相比于氨氯地平+吲达帕胺组，GMRx 2组家庭收缩压/舒张压多降低4.4/3.6 mmHg（P＜0.0001）、诊室收缩压/舒张压多降低6.3/4.5 mmHg（P＜0.0001）。 事实上，GMRx 2组的降压优势在治疗第6周时就有所体现，如下图所示，第6周起，GMRx 2组无论收缩压还是舒张压，均低于其他组。这意味着，即使是一半剂量的GMRx 2，也具有明显的降压优势。 ▲GMRx 2组（蓝色圆圈）、替米沙坦+吲达帕胺组（橙色方块）、替米沙坦+氨氯地平组（蓝色米字）、氨氯地平+吲达帕胺组（红色三角）的家庭血压（左）和诊室血压（右）变化（图片来源：参考文献[1]） 安全性方面，治疗第12周时，GMRx 2组、替米沙坦+吲达帕胺组、替米沙坦+氨氯地平组、氨氯地平+吲达帕胺组分别有2%（11/551）、1%（4/276）、1%（3/282）、1%（4/276）的受试者因不良事件退出治疗，且组间差异均无统计学意义。本次研究患者治疗依从性较高（96%）。 《柳叶刀》发表的同期社论指出，未来还需考虑GMRx 2在严重高血压患者中的应用疗效，特别是难治性高血压患者，以及还需关注GMRx 2是否有利于降低心血管风险。总之，无论是标准剂量的GMRx 2还是一半剂量的GMRx 2，其降压效果均优于替米沙坦、吲达帕胺、氨氯地平药两两组合，且用药安全，耐受性好。 参考资料 [1] Anthony Rodgers, Abdul Salam, Aletta E Schutte, et al. Efficacy and safety of a novel low-dose triple single-pill combination of telmisartan, amlodipine and indapamide, compared with dual combinations for treatment of hypertension: a randomised, double-blind, active-controlled, international clinical trial. The Lancet, 2024, 404(10462): 1536-1546. DOI: 10.1016/S0140-6736(24)01744-6 [2] Maria Antonopoulou, Konstantinos Chliveros. The Lancet, 2024, 404(10462): 1496-1498. DOI: 10.1016/S0140-6736(24)02072-5 撰文 | 阿拉斯加宝 编辑 | 阿拉斯加宝 ●震撼！医生感慨：我们的工作量猛增，到手工资反而变少，真心扛不动了！医生两项工作量都在增加！我国住院率突破20%！为啥总喜欢住院呀 ●深度热议！病人进了手术室，医生索要3000元“专家费”，不给不做手术？卫健委回应！近3成医生飞刀过，说不清的飞刀，该如何面对？ ●Nature重磅：饭吃“六分饱”和间歇性禁食能延寿，但是要付出代价的！谷歌旗下抗衰老研究公司最新发文 版权说明：梅斯医学（MedSci）是国内领先的医学科研与学术服务平台，致力于医疗质量的改进，为临床实践提供智慧、精准的决策支持，让医生与患者受益。欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。 点击下方「阅读原文」 立刻下载梅斯医学APP！

Phase III trial results of novel triple combination pill for hypertension published in The Lancet Novel combination pill significantly reduced blood pressure and improved control rates vs dual therapy, with good tolerability and no increase in adverse event related withdrawalsTriple combination approach aligns with latest European Society of Cardiology hypertension guidelines recommending increased use of combination therapies Subject to regulatory review, following New Drug Application (NDA) filed with FDA in August, GMRx2 would be the first triple combination approved for initial treatment of hypertension London, UK, 18 October 2024 – George Medicines, a late-stage biopharmaceutical company focused on addressing significant unmet needs in cardiometabolic disease treatment, today announced that The Lancet has published results from its pivotal Phase III clinical trial of GMRx2. A proprietary combination of three best-in-class medicines, telmisartan, amlodipine and indapamide, developed in an ultra-low dose (triple quarter-dose), low-dose (triple half-dose), and triple standard-dose options, GMRx2 was compared with dual combinations, for the treatment of hypertension (high blood pressure), including initiation of treatment. The triple combination’s multi-mechanism approach is designed to deliver optimal efficacy and safety while promoting patient adherence. The research, “Efficacy and safety of a novel low-dose triple single-pill combination of telmisartan, amlodipine and indapamide, compared with dual combinations for treatment of hypertension: a randomised, double-blind, active-controlled, international clinical trial”, is published in the 19 October issue of The Lancet. The international trial, conducted in seven countries, met all primary efficacy and safety endpoints: GMRx2 was more effective than each dual therapy, significantly reducing both home- and clinic-measured blood pressure (BP) and improving BP control rates, with both standard- and half-dose forms.GMRx2 half-dose achieved 63% clinic BP control <140/90 mmHg, which rose to 74% at the end of follow-up on GMRx2 standard-dose – superior to all three dual combinations at standard-dose (53-61%).Assessed against more stringent BP control rates of <130/80 mmHg, GMRx2 standard dose achieved 56% control rates, again clinically and statistically superior to all three dual combinations (33-44%).Tolerability was good, with no increase in withdrawal from treatment due to adverse events. This treatment approach aligns with recently updated European Society of Cardiology (ESC) guidelines for hypertension management1, which recommend lower blood pressure levels to begin treatment among those at raised risk and greater use of combination therapy, starting off with dual low-dose followed by a triple low -dose therapy. Chair of the trial’s steering committee, Dr. Paul Whelton, Show Chwan Chair of Global Public Health at Tulane University, New Orleans, Louisiana, and President of the World Hypertension League, commented: “This trial, conducted across seven countries and diverse populations, demonstrates that GMRx2 provides significantly better blood pressure control compared to dual combinations, while maintaining an excellent safety profile. The findings are particularly noteworthy as they show efficacy at lower blood pressure levels, aligning with the latest guideline recommendations. This new single-pill combination has the potential to address the critical need for more effective and tolerable treatment options to achieve and maintain blood pressure control in the many patients who remain uncontrolled on current therapies.” Dr. Anthony Rodgers, Chief Medical Officer of George Medicines, and Professorial Fellow at The George Institute for Global Health, said: “These findings, now published in The Lancet, provide robust evidence for the potential of GMRx2 to transform hypertension management. The superior efficacy of this triple combination therapy compared to dual combinations, coupled with its good tolerability, addresses key challenges in current hypertension treatment approaches and directly supports recent guideline recommendations. Subject to regulatory approval, we believe GMRx2 could play a crucial role in addressing the global burden of hypertension and improving patient outcomes.” These results, along with data from other recent trials, including the VERONICA trial in Nigeria, funded by the National Health and Medical Research Council (NHMRC) of Australia, supported by The George Institute for Global Health and recently published in JAMA, and a placebo-controlled Phase III study recently published in the Journal of the American College of Cardiology, provide a comprehensive body of evidence supporting the efficacy and safety of GMRx2 across various patient populations and dosing regimens. In August 2024 George Medicines announced its submission to the US Food and Drug Administration (FDA) of a New Drug Application (NDA) for GMRx2. Data from GMRx2’s clinical development program will support additional global regulatory filings. 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. The Company’s GMRx2 development program built on earlier research by The George Institute, including the 700-patient TRIUMPH trial undertaken in Sri Lanka in 2016/17, which found that among patients with mild to moderate hypertension, treatment with a low-dose triple combination pill led to an increased proportion of patients achieving their target blood pressure goal versus usual care. Ends About the clinical trialA Phase III trial among 1,385 patients in Australia, Czech Republic, New Zealand, Poland, Sri Lanka, UK and the US, standard- and half-dose forms of GMRx2 were tested against dual combinations of its component drugs. The trial’s primary efficacy outcome was the difference between GMRx2 and its comparators in home blood pressure change from randomization to week 12. The head-to-head trial provides the first large scale comparison of a low- and standard-dose triple combination pill and its dual combinations at the same doses. It assessed the safety and efficacy of the triple combination among patients with starting blood pressure levels that were considerably lower than those in previous trials. About hypertension (high blood pressure)Globally, more than one billion adults have hypertension2. Many diagnosed patients aren’t achieving sufficient blood pressure control because they are on inadequate therapy, aren’t receiving the right combination of medicines at the right doses or aren’t taking their treatment as prescribed or continuing their treatment in the long term. The major, globally recognized treatment guidelines3 recommend the use of fixed dose combination therapy for most patients with hypertension, including for first-line treatment and yet, in practice, newly diagnosed patients will often still be prescribed monotherapy treatment. This is despite a broad evidence base indicating that, individually, blood pressure medicines are only modestly effective at reducing blood pressure, even at high doses, and most patients will require two or more medicines to achieve control. As dosage of hypertension drugs is increased, so too are side effects, which can preclude the use of high doses for many patients. These side effect challenges, alongside the management of multiple hypertension medicines being taken together with treatments for other conditions, can significantly impact treatment compliance and adherence, including failure to take medications as prescribed and to persist on long-term therapy. About George Medicines George Medicines is a late-stage biopharmaceutical company addressing significant unmet need in the treatment of cardiometabolic diseases with innovative combinations of best-in-class existing treatments, designed for optimal efficacy and safety. Combining best-in-class molecules from existing medicines in novel low-dose formulations, George Medicines is developing innovative and proprietary treatments to be more efficacious, safer and accessible than currently available treatment options. These multi-mechanism, single-pill combinations offer the potential to bring significant improvements in clinical outcomes and therapy adherence in patients with cardiometabolic disorders, including hypertension and diabetes, each of which remain the leading causes of premature death and disability worldwide. The Company’s lead candidate, GMRx2, has completed a Phase III development program for the treatment of hypertension, including first-line therapy, and a global trial focused on the prevention of recurrent intracerebral hemorrhage (the most severe type of stroke) is underway. 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. References 2024 ESC Guidelines for the management of elevated blood pressure and hypertension https://www.escardio.org/Guidelines/Clinical-Practice-Guidelines/Elevated-Blood-Pressure-and-HypertensionWorld Health Organization Hypertension factsheet https://www.who.int/news-room/fact-sheets/detail/hypertension2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines https://www.ahajournals.org/doi/10.1161/HYP.0000000000000065; WHO Guideline for the pharmacological treatment of hypertension in adults https://iris.who.int/bitstream/handle/10665/344424/9789240033986-eng.pdf; 2024 ESC Guidelines for the management of elevated blood pressure and hypertension https://www.escardio.org/Guidelines/Clinical-Practice-Guidelines/Elevated-Blood-Pressure-and-Hypertension Media contacts ICR Consilium David Daley, Lindsey Neville, Isabelle Abdou georgemedicines@consilium-comms.com; Tel: +44 (0) 203 709 5700