Triple Combination Therapy Superior to Single in Lowering Blood Pressure, With Paul Whelton, MD

GMRx2, a novel low-dose triple combination of antihypertensive drugs in a single pill, effectively lowered blood pressure (BP) compared to placebo and dual combinations in an open-label extension of a clinical trial.1

These data were presented at the American Heart Association’s (AHA) Scientific Sessions 2025 in New Orleans, Louisiana, by Anthony Rodgers, MBChB, chair of clinical epidemiology at Imperial College London and professor of global health at the University of South Wales Sydney.1

The editorial team at HCPLive sat down with Paul Whelton, MD, Show Chwan Health System Endowed Chair in Public Health at Tulane University and an investigator for the study, to discuss the world’s historical difficulties in managing hypertension. Whelton discussed the importance of optimizing blood pressure and the comparative efficacy of triple therapy compared to single.

“We published a large, randomized control meta-analysis in the Lancet recently. And what it showed is that with monotherapy, with any of the standard agents we use for blood pressure, you’re going to lower systolic blood pressure by about nine millimeters,” Whelton told HCPLive. “That’s not enough. That is very rarely enough. Most people are going to need triple therapy, and if you could give that in a single pill, at a reasonable price, it’s a fantastic way to quickly control your blood pressure.”

After a 4-week, double-blind, placebo-controlled, randomized, multi-country phase, the open-label extension was conducted at 2 sites in Nigeria and 9 in Sri Lanka. Participants who had completed the randomized double-blind phase with no contraindications to the GMRx2-based treatment and who were willing to continue on GMRx2-based treatment until 52 weeks were eligible to participate.2

A total of 53 patients were enrolled in the extension and were immediately started on GMRx2 ¼. Investigators initially conducted clinic visits after 2 and 4 weeks of treatment, and at 3 month intervals thereafter. If participants had a recent home mean systolic or diastolic blood pressure ≥130 and/or ≥80 mmHg, they were up-titrated to GMRx2 ½ and, if necessary, up to GMRx2 standard.2

Patients measured their blood pressure at home based on AHA guidance; readings were encrypted and automatically sent to the trial database. Measurements were taken over 4 consecutive days before a trial visit, weekly afterwards, and thrice every morning and evening. Investigators also investigated blood pressure in the clinic at all visits. Lab tests for serum electrolytes and creatinine were performed at week 4, 8, 16, and 52.2

The primary efficacy outcome was the percent of participants with home blood pressure control to <130/80 mmHg at week 52, and the primary safety outcome was the percent of participants who discontinued treatment due to an adverse event. Secondary outcomes included the percentage of patients with home blood pressure control to <130/80 mmHg and <135/85 mmHg, clinic blood pressure control to <140/90 mmHg at week 52, and serious adverse events, among others.2

A total of 48 patients completed the open-label extension; of these, baseline mean home and clinic blood pressure levels were 129/79 mmHg and 131/83 mmHg, respectively. At week 4, mean home and clinic blood pressure were reduced to 121/78 mmHg and 126/79 mmHg, respectively. By week 52, mean home blood pressure was reduced to 120/78 mmHg, while mean clinic blood pressure was 122/77 mmHg.1

Additionally, at week 52, the proportion of participants receiving GMRx2 ¼, GMRx2 ½, and GMRx2 standard doses were 53%, 27%, and 22%, respectively. Only 3 patients needed add-on therapy, and tolerability was good; no patients discontinued treatment due to an adverse event.1

“We got control very quickly and it lasted throughout the year. There were no truly serious adverse events,” Whelton said. “In that sense, it was a nice demonstration that you can get good blood pressure control quickly with triple therapy, you can maintain it for a long period of time, and it’s a very safe approach.”

References

1. Rodgers A. Long-Term Efficacy and Safety of a Novel Low-Dose Triple Single-Pill Combination for the Treatment of Hypertension. Presented at the American Heart Association’s Scientific Sessions 2025. New Orleans, Louisiana. November 8-10, 2025.

2. Salam A, de Silva HA, Ojji D, et al. Long-Term Efficacy and Safety of a Novel Low-Dose Triple Single-Pill Combination for the Treatment of Hypertension. Glob Heart. 2025;20(1):102. Published 2025 Oct 31. doi:10.5334/gh.1481