MedicalResearch.com Interview with: [caption id="attachment_72419" align="alignleft" width="200"] Prof. Moo-Yong Rhee[/caption] Professor Moo-Yong Rhee MD, PhD. Cardiology, Dongguk University Ilsan Hospital College of Medicine, Dongguk University Goyang-si, Gyeonggi-do, Korea MedicalResearch.com: What is the background for this study? Response: Hypertension remains one of the leading causes of cardiovascular morbidity and mortality worldwide. Major challenges in its initial treatment include therapeutic inertia, reliance on stepwise dose escalation of single agents, and reduced adherence due to dose-related adverse effects. These limitations often delay optimal blood pressure control. To address these issues, the concept of low-dose combination therapy was proposed, based on the rationale that combining multiple agents at lower doses may enhance efficacy while minimizing side effects. Although several studies have supported this concept, systematic translational research and confirmatory clinical trials were needed before widespread clinical implementation. The recently completed APOLLO-301 and APOLLO-302 trials were confirmatory, randomized, phase 3 studies designed to evaluate the efficacy and safety of a single-pill ultra-low-dose triple combination therapy, conducted in accordance with regulatory standards. This formulation combined three antihypertensive agents (amlodipine (1.67 mg), losartan (16.67 mg), and chlorthalidone (4.17 mg)) each at approximately one-third of its standard dose. The triple combination was directly compared with standard-dose monotherapy (amlodipine 5 mg or losartan 50 mg). After 8 weeks of treatment, the ultra-low-dose triple combination achieved blood pressure reductions comparable to those of amlodipine 5 mg and significantly greater than those of losartan 50 mg, while maintaining good tolerability. These findings support the potential role of ultra-low-dose triple therapy as an effective initial treatment strategy for patients with mild-to-moderate hypertension.