The Westmead Applied Research Centre, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia; The George Institute for Global Health, UNSW, Sydney, NSW, Australia.
The Westmead Applied Research Centre, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia; The George Institute for Global Health, UNSW, Sydney, NSW, Australia.
Am Heart J. 2021 Jan;231:56-67. doi: 10.1016/j.ahj.2020.09.017. Epub 2020 Oct 2.
High blood pressure is the leading cause of preventable morbidity and mortality globally. Many patients remain on single-drug treatment with poor control, although guidelines recognize that most require combination therapy for blood pressure control. Our hypothesis is that a single-pill combination of 4 blood pressure-lowering agents each at a quarter dose may provide a simple, safe, and effective blood pressure-lowering solution which may also improve long-term adherence. The Quadruple UltrA-low-dose tReaTment for hypErTension (QUARTET) double-blind, active-controlled, randomized clinical trial will examine whether ultra-low-dose quadruple combination therapy is more effective than guideline-recommended standard care in lowering blood pressure. QUARTET will enroll 650 participants with high blood pressure either on no treatment or on monotherapy. Participants will be randomized 1:1 and allocated to intervention therapy of a single pill (quadpill) containing irbesartan 37.5 mg, amlodipine 1.25 mg, indapamide 0.625 mg, and bisoprolol 2.5 mg or to control therapy of a single identical-appearing pill containing irbesartan 150 mg. In both arms, step-up therapy of open-label amlodipine 5 mg will be provided if blood pressure is >140/90 at 6 weeks. The primary outcome is the difference between groups in the change from baseline in mean unattended automated office systolic blood pressure at 12-week follow-up. The primary outcome and some secondary outcomes will be assessed at 12 weeks; there is an optional 12-month extension phase to assess longer-term efficacy and tolerability. Our secondary aims are to assess if this approach is safe, has fewer adverse effects, and has better tolerability compared to standard care control. QUARTET will therefore provide evidence for the effectiveness and safety of a new paradigm in the management of high blood pressure.
高血压是全球可预防发病率和死亡率的主要原因。尽管指南认识到大多数患者需要联合治疗来控制血压，但许多患者仍接受单一药物治疗，血压控制不佳。我们的假设是，将四种降压药物各以四分之一剂量组合成一种单片复方制剂，可能提供一种简单、安全且有效的降压解决方案，也可能改善长期依从性。四重超低剂量降压治疗高血压（QUARTET）双盲、活性对照、随机临床试验将研究超低剂量四联疗法是否比指南推荐的标准治疗更能有效降低血压。QUARTET 将招募 650 名高血压患者，他们要么未接受治疗，要么接受单一药物治疗。参与者将以 1:1 的比例随机分组，接受干预治疗，即含有厄贝沙坦 37.5 mg、氨氯地平 1.25 mg、吲达帕胺 0.625 mg 和比索洛尔 2.5 mg 的单一药丸（四联丸）或接受对照治疗，即含有厄贝沙坦 150 mg 的单一外观相同的药丸。在这两种治疗组中，如果 6 周时血压>140/90mmHg，将提供开放标签氨氯地平 5mg 的阶梯式治疗。主要结局是 12 周随访时，未经监测的自动诊室收缩压从基线的变化两组之间的差异。主要结局和一些次要结局将在 12 周时评估；有一个可选的 12 个月扩展阶段，以评估长期疗效和耐受性。我们的次要目标是评估这种方法是否安全、不良反应更少且耐受性更好，与标准治疗对照相比。QUARTET 将为高血压管理新模式的有效性和安全性提供证据。
