Author Interviews, Blood Pressure - Hypertension, JACC / 15.02.2026
APOLLO Trials Support Potential Role of Ultra-Low-Dose Triple Therapy as Initial Strategy for Mild-to-Moderate Hypertension
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.
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.
Dr. Finn[/caption]
Aloke V. Finn MD
Medical Director/Chief Scientific Officer
CVPath Institute Inc.
Gaithersburg, MD 20878
MedicalResearch.com: What is the background for this study?
Response:Transcatheter left atrial appendageal closure (LAAC) has become an established therapeutic approach for prevention of stroke in subjects with non-valvular atrial fibrillation who are ineligible for long-term oral anticoagulation. Device-related thrombus (DRT), developing after LAAO procedures occurs in a small proportion but patients receiving these devices but is associated with critical embolic events such as ischemic stroke. Thrombogenicity and delayed endothelialization of fabric play a role in the development of DRT. Fluorinated polymers are known to have thromboresistant properties which may favorably modify blood biomaterial interactions of a LAAO device.
In this study we compared the thrombogenicity and endothelial coverage (EC) after left atrial appendage occlusion (LAAO) between a novel fluoropolymer-coated Watchman (FP-WM (Watchman FLX PRO) and the conventional uncoated Watchman FLX (WM).
Dr. Bayes-Genis[/caption]
Antoni Bayes-Genis, MD, PhD, FESC, FHFA
Head, Heart Institute. Hospital Universitari Germans Trias i Pujol
Full Professor, Autonomous University Barcelona
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Omega-3 fatty acids are incorporated into the phospholipids of cellular membranes, including cardiac contractile cells, and have a wide range of demonstrated physiological effects. Several potential mechanisms have been investigated, including antiarrhythmic, anti-inflammatory, and endothelial.
Omega-3 fatty acids lower heart rate and improve heart rate variability, both associated with lower sudden cardiac death risk, one of the complications that may occur after a myocardial infarction.
Increased omega-3 fatty acids also enhance arterial elasticity by increasing endothelium-derived vasodilators, which is associated with blood pressure–lowering effects.
They also have a cardioprotective effect on platelet-monocyte aggregation, and lower triglyceride levels.
