Point-of-care clinical trial finds two blood pressure drugs equally effective: the Veterans Affairs-funded Diuretic Comparison Project

A large real-world clinical trial embedded in routine clinical care of US veterans with high blood pressure shows no difference between two first-line thiazide diuretics for the prevention of cardiovascular disease or non-cancer death.

The US Department of Veterans Affairs (VA) Cooperative Studies Program announced at the close of 2022 that their innovative real-world clinical trial, the Diuretic Comparison Project (DCP), demonstrated equal efficacy for cardiovascular outcomes for the common first-line blood pressure drugs chlorthalidone (CTD) and hydrochlorothiazide (HCTZ). Embedded in the usual care of veterans nationwide living with hypertension, the novel point-of-care study methodology elucidated this RWE efficiently at low-cost without additional staff or extra-burden on veteran participants.

“Because of the number of veterans VA cares for and our systemwide electronic medical record, we were able to embed this massive clinical trial within day-to-day care without any additional burden to the thousands of veterans who volunteered for this study,” explained Rachel Ramoni, VA’s Chief R&D Officer. “The result is important evidence of how these widely-used medications work in the real world.”

CTD and HCTZ are both thiazide diuretics that have been in use for over 50‑years and each are considered a first-line treatment for hypertension. They are commonly known as ‘water pills’ as they act to help the body rid itself of excess fluid, which can lower blood pressure. Recent clinical guidelines say CTD may be more effective than HCTZ for treatment of hypertension but, conversely, most clinicians prescribe HCTZ over CTD. Prior to the VA DCP study, no randomized controlled data existed comparing these two diuretics on cardiovascular outcomes.

The VA DCP was a first-of-its-kind real-world pragmatic clinical trial. Its novel approach was its point-of-care methodology, whereby as much of the study procedures as possible were embedded into the routine medical care of veterans. The design allowed participation from across the country with no additional staff and placed no extra-burden on veterans who participated, resulting in a streamlined and efficient, massive trial.

The DCP was conducted at 537 US VA medical centers and community clinics, and enrolled over 4,000 providers. Of 13,500 participant veterans with high blood pressure who were taking HCTZ at baseline, individuals were randomized to stay on their current dose of HCTZ or take an equivalent dose of CTD. The main study compared CTD 12.5mg to HCTZ 25mg. The team found no difference between the two drugs at these lower doses for the prevention of cardiovascular disease or non-cancer death, which included heart attack, stroke, heart failure, or lack of blood flow requiring medical intervention.

“We were able to compare two commonly prescribed generic drugs using a low-cost methodology,” said principal investigator Dr. Areef Ishani, Director of the Minneapolis Primary Care and Specialty Care Integrated Care Community at Minneapolis VA. “This trial has shown that large, embedded trials are operationally feasible. They can be incorporated into the clinical workflow of providers by leveraging the electronic health record and other existing infrastructure.”

The results of the study were published in the New England Journal of Medicine and can be read here.