BACKGROUND: Single-pill combinations of 3 or more low-dose blood pressure (BP)-lowering drugs hold promise for initial or early treatment of hypertension.
OBJECTIVES: We conducted a placebo-controlled trial of a new single-pill combination containing low doses of telmisartan, amlodipine, and indapamide in 2 dose options to assess efficacy and safety.
METHODS: This international, randomized, double-blind, placebo-controlled, parallel-group trial enrolled adults with hypertension receiving 0 to 1 BP-lowering drugs. After a 2-week placebo run-in during which any BP-lowering medication was stopped, participants were eligible if home systolic BP (SBP) was 130 to 154 mm Hg. Participants were randomized in a 2:2:1 ratio to GMRx2 ¼ dose (telmisartan 10 mg/amlodipine 1.25 mg/indapamide 0.625 mg), GMRx2 ½ dose (telmisartan 20 mg/amlodipine 2.5 mg/indapamide 1.25 mg), or placebo. The primary efficacy outcome was difference in change in home SBP from randomization to week 4, and primary safety outcome was treatment discontinuation due to an adverse event.
RESULTS: From June 14, 2021 to October 18, 2023, a total of 295 participants (mean age: 51 years; 56% female) were randomized and 96% completed the trial. Baseline mean home BP was 139/86 mm Hg and clinic BP was 138/86 mm Hg after placebo run-in. The placebo-corrected least square mean differences in home SBP at Week 4 were -7.3 mm Hg (95% CI: -4.5 to -10.2) for GMRx2 ¼ dose and -8.2 mm Hg (95% CI: -5.2 to -11.3) for GMRx2 ½ dose; reductions for clinic BP were 8.0/4.0 and 9.5/4.9 mm Hg. At Week 4, clinic BP control (<140/90 mm Hg) was 37%, 65%, and 70% for placebo, GMRx2 ¼ dose, and GMRx2 ½ dose, respectively (both doses P < 0.001 vs placebo). Placebo, GMRx2-triple ¼, and GMRx2 ½ treatment discontinuation due to an adverse event occurred in 1 (1.6%), 0, and 6 (5.1%), respectively; out of normal range serum sodium or potassium was observed in 4 (6.3%), 12 (10.6%), and 12 (10.1%), respectively, but no participant had a 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 and none in the GMRx2 ¼ group.
CONCLUSIONS: In a population with mild-to-moderate BP elevation, both dose versions of the novel low-dose triple single-pill combination showed good tolerability and clinically relevant BP reductions compared with placebo. (Efficacy and Safety of GRMx2 Compared to Placebo for the Treatment of Hypertension: NCT04518306).
| Discipline Area | Score |
|---|---|
| Family Medicine (FM)/General Practice (GP) |  |
| General Internal Medicine-Primary Care(US) | |
| Internal Medicine | |
| Cardiology | |
| Endocrine | |
295 participants (mean age: 51 years; 56% female) were randomized in this trial and 96% completed it. Baseline home and clinic blood pressures (BP) were 139/86 mm Hg and 138/86 mm Hg, respectively. After four weeks, the placebo-corrected reductions in home systolic BP were 7.3 mm Hg for GMRx2 1/4 dose and 8.2 mm Hg for GMRx2 1/2 dose. Clinic BP control (<140/90 mm Hg) was achieved by 37% on placebo, 65% on GMRx2 1/4, and 70% on GMRx2 1/2. Both doses were well-tolerated and had clinically relevant BP reductions.
This is an important study challenging a concept for initiating antihypertensive therapy in mild-to-moderate hypertension with a novel low-dose triple single-pill combination. The findings showing that this approach was effective compared with placebo and well-tolerated (minimizing occurrence of adverse effects) are introducing a new paradigm in starting antihypertension treatments in these populations.
This builds on previous evidence for using lower doses of multiple BP agents, rather than the older recommendation to maximise dose of one agent prior to adding another agent.
The idea behind this study is old, but robust studies like the STITCH trial showed combinations work best for optimal control. As always, logistics and cost will be very important for wide acceptance of a polypill; previous response and acceptance of polypills has been disappointing.