NEJM: The new "burden-free" study method found that both antihypertensive drugs were equally effective

Researchers at the University of Minnesota School of Medicine, in collaboration with Veterans Affairs, published a large clinical trial in the New England Journal of Medicine and found that the antihypertensive drug chlorthalidone (CTD) is no better
than hydrochlorothiazide (HCTZ) at preventing cardiovascular disease or non-cancer death.

Current clinical guidelines suggest that CTD may be more effective than HCTZ in lowering blood pressure, but this suggestion is not directly supported by evidence
.
Both drugs have been used for more than 50 years and are considered first-line treatments for high blood pressure and fall under the category of thiazide diuretics — often referred to as water pills
.
They are used to help the body flush out excess fluid, which lowers blood pressure
.

"We were able to compare two commonly used prescription generics using a low-cost method," said lead investigator, Dr.
Areef Ishani, M.
D.
, vice president and professor at the University of Michigan School of Medicine and director of
the Minneapolis Veterans Affairs Health Care System's Primary Care and Specialty Care Integrated Care Community.
"This trial shows that large-scale embedded trials are operationally feasible
.
By leveraging electronic health records and other existing infrastructure, they can be incorporated into providers' clinical workflows
.
”

The Diuretic Comparison Program (CSP 597) is a large practical clinical trial conducted at
537 Veterans Affairs (VA) medical centers and community clinics in the United States.
The trial enrolled more than 4,000 providers and 13,500 veterans with hypertension who took HCTZ at baseline
.

Study participants were randomly divided into:

• Keep the current dose of HCTZ

• Or take the same amount of CTD

95% of the study participants took a lower dose of HCTZ, so the main study comparison was 12.
5 mg CTD versus 25 mg HCTZ.

The team found that ways to prevent cardiovascular disease or non-cancer deaths, including heart attacks, strokes, heart failure, or inadequate blood flow that require medical intervention, include:

• There was no difference between the two drugs at low doses

• The risk of hypokalemia increased slightly in the CTD group, but this was quickly resolved by potassium supplementation
  .
  

"In 2020, Medicare reported that about 1.
5 million people were prescribed CTDs and 11.
5 million people were prescribed HCTZ
despite guideline recommendations.
The discrepancy between clinical guidelines and actual use may be related to a greater risk of adverse effects for CTD, but there is no clear evidence of a difference in cardiovascular outcomes," said Dr.
Ishani
.

The study was funded
by the Department of Veterans Affairs Collaborative Research Program.