A novel low-dose triple combination therapy, known as GMRx2, has demonstrated significant effectiveness in lowering blood pressure compared to both placebo and dual drug combinations. This finding emerged from an open-label extension of a clinical trial, presented at the American Heart Association’s (AHA) Scientific Sessions 2025, held in New Orleans, Louisiana. The study was led by Anthony Rodgers, MBChB, who chairs clinical epidemiology at Imperial College London and is a professor of global health at the University of South Wales Sydney.
Dr. Paul Whelton, who serves as the Show Chwan Health System Endowed Chair in Public Health at Tulane University, participated as an investigator in the study. He highlighted the ongoing challenges in managing hypertension and the importance of effective treatment strategies. In a discussion with the editorial team at HCPLive, Whelton emphasized the superiority of triple therapy over single-agent treatments. “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 explained. “That’s not 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.”
The open-label extension followed an initial four-week, double-blind, placebo-controlled phase, conducted across two sites in Nigeria and nine in Sri Lanka. Participants who completed the randomized phase without any contraindications to the GMRx2 treatment were eligible to enroll in the extension. A total of 53 patients began treatment with GMRx2 1⁄4, and follow-up visits occurred at two and four weeks, and then at three-month intervals.
During the study, participants monitored their blood pressure at home in accordance with AHA guidelines. Readings were securely transmitted to a trial database, with measurements taken over four consecutive days prior to trial visits. Participants were subsequently monitored weekly and three times each morning and evening. Blood pressure was also assessed during clinic visits, with lab tests for serum electrolytes and creatinine conducted at weeks four, eight, sixteen, and fifty-two.
The primary efficacy outcome aimed to determine the percentage of participants achieving home blood pressure control below 130/80 mmHg at week 52. Primary safety outcomes assessed the percentage of participants who discontinued treatment due to adverse events. Secondary outcomes included various blood pressure control targets and the incidence of serious adverse events.
Of the 53 enrolled patients, 48 completed the open-label extension. Their baseline mean home blood pressure was recorded at 129/79 mmHg, while clinic measurements were 131/83 mmHg. After just four weeks on the treatment, mean home and clinic blood pressure levels decreased to 121/78 mmHg and 126/79 mmHg, respectively. By week 52, these numbers improved further, with mean home blood pressure reaching 120/78 mmHg and clinic blood pressure at 122/77 mmHg.
At the conclusion of the study, the distribution of participants receiving different dosages of GMRx2 was 53% on GMRx2 1⁄4, 27% on GMRx2 1⁄2, and 22% on the standard dose. Remarkably, only three patients required additional therapy, and tolerability was reported as excellent, with no patients discontinuing treatment due to adverse events.
Whelton noted the rapid and sustained blood pressure control achieved through GMRx2. “We got control very quickly and it lasted throughout the year. There were no truly serious adverse events,” he stated. “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.”
These promising results suggest that GMRx2 could play a significant role in the future of hypertension management, offering a practical solution for those struggling to control their blood pressure effectively.
