Dr. Mustafa Lütfi Yavuz, Dr. Mehmet Aydoğan

Study Title:
GMRx2 - Efficacy and Safety of a Novel Triple Single Pill Combination

Published at Conference:
ESC 2024

Link:
https://www.jacc.org/doi/10.1016/j.jacc.2024.08.025

Introduction: The combination of three or more antihypertensive agents in low doses within a single tablet formulation is emerging as a promising strategy for the initiation or early-stage treatment of hypertension.

Objective: The GMRx2 trial, a placebo-controlled study, has been designed to evaluate the efficacy and safety of a novel low-dose combination containing telmisartan, amlodipine, and indapamide in two distinct dosage options. This study aims to investigate the potential benefits and possible adverse effects of this combination in the management of hypertension.

Methods: In this international, randomized, double-blind, placebo-controlled trial, hypertensive adults with a systolic blood pressure (SBP) of 130-154 mm Hg measured at home, who were on 0-1 antihypertensive medications, were included. Following a two-week placebo run-in period, participants were randomized in a 2:2:1 ratio to receive either ¼ dose GMRx2 (telmisartan 10 mg/amlodipine 1.25 mg/indapamide 0.625 mg), ½ dose GMRx2 (telmisartan 20 mg/amlodipine 2.5 mg/indapamide 1.25 mg), or placebo. The primary efficacy outcome was the difference in home-measured SBP change from randomization to week 4, while the primary safety outcome was defined as treatment discontinuation due to an adverse event.

Results: Among the 295 participants enrolled, with a mean age of 51 years, 96% completed the study. At baseline, after the placebo run-in period, the average home-measured blood pressure was 139/86 mm Hg, and the average clinic-measured blood pressure was 138/86 mm Hg. At week 4, the reduction in home-measured mean SBP was -7.3 mm Hg (95% CI: -4.5 to -10.2) for the GMRx2 ¼ dose and -8.2 mm Hg (95% CI: -5.2 to -11.3) for the GMRx2 ½ dose; the reductions in clinic-measured blood pressure were 8/4 and 9.5/4.9 mm Hg, respectively. The rates of achieving blood pressure control (<140/90 mm Hg) in the clinic were 37%, 65%, and 70% for the placebo, GMRx2 ¼ dose, and GMRx2 ½ dose groups, respectively (p-value <0.001 for both doses vs. placebo). Treatment discontinuation due to adverse events occurred in 1 (1.6%), 0, and 6 (5.1%) participants in the placebo, GMRx2 ¼ dose, and GMRx2 ½ dose groups, respectively; abnormal serum sodium or potassium levels were observed in 4 (6.3%), 12 (10.6%), and 12 (10.1%) participants, respectively, although no participant had serum sodium <130/>150 mmol/L or potassium <3.0/>6.0 mmol/L. Serious adverse events were reported by 2 participants in the placebo and GMRx2 ½ groups, with no serious adverse events reported in the GMRx2 ¼ group.

Conclusion: In a population with mild to moderate hypertension, both dosage variants of the novel low-dose triple single-pill combination were well-tolerated and provided clinically significant reductions in blood pressure compared to placebo.

Commentary:
The GMRx2 trial provides valuable insights into the efficacy and safety of a novel low-dose triple combination therapy for hypertension. The significant reductions in systolic blood pressure observed in both dosage groups, combined with a favorable safety profile, highlight the potential of this approach in managing mild to moderate hypertension. The study's robust design and positive short-term results suggest that such combinations could be a promising option for early hypertension treatment, though longer-term studies are needed to confirm these findings.