Research Highlights:-

• In a study comparing the effectiveness of two antihypertensive medications (both diuretics) among elderly veterans, there were no differences in cardiovascular outcomes or non-cancer mortality.

• There was also no difference in heart attack, stroke, heart failure or other cardiovascular outcomes.

• In a small subgroup (10%) of people with a history of heart attack or stroke, there was a 27% reduction in heart attack, stroke, and death from heart failure when treated with clotalidone. However, people with high blood pressure who have not had a heart attack or stroke have a 12 percent increased risk of cardiovascular disease while taking Clothalidone. It’s not clear how this subgroup result will translate into the overall trial, as it showed no difference between the two drugs, researchers said.

to 9:46 a.m. CT/10:46 a.m. ET, Sat. November 5, 2022

(NewMediaWire– November 05, 2022 – CHICAGO: Two common diuretics used to control high blood pressure had no difference in cardiovascular outcomes, including death, according to a Late Science study presented today at the American Heart Association’s Scientific Sessions 2022. In Chicago and in Practice, November 5-7, 2022, is the premier exchange for the latest scientific advances in cardiovascular science, research and evidence-based clinical practice.

Among more than 13,500 study participants, those treated with the antihypertensive chlorthalidone had no differences in cardiovascular outcomes or non-cancer-related deaths compared with those treated with hydrochlorothiazide. However, in a small group with a history of heart attack or stroke, those taking Clothalidone had an average 27 percent lower risk of heart disease and death.

The results are from a study investigating whether clotalidone is superior to hydrochlorothiazide in preventing cardiovascular disease in people with high blood pressure. As of 2011 American Heart Association Heart Disease and Stroke Statistics 2022 Update, about half of American adults have high blood pressure, which is the leading cause of heart disease. Chlorthalidone and hydrochlorothiazide have been prescribed diuretics for over 50 years and are considered first-line treatment for hypertension. Based on previous studies and other studies, Clothalidone did a better job of controlling blood pressure over 24 hours than Hydrochlorothiazide, and many experts believe that Clothalidone is more effective in reducing the risk of heart disease.

The story continues

Researchers designed the Dietary Comparison Project (DCP) as a point-of-care clinical trial to allow participants and healthcare professionals to know which drug was prescribed and administer the drug in the real world. The point of care offered several unique features to the trial, explained Arf Ishani, co-author of the study, director of the Minneapolis Primary Care and Specialty Care Integrated Care Community and director of the VA Midwest Healthcare Network. Minneapolis

“Because we have integrated this trial into primary care clinics, patients can continue with their usual care by their usual care team,” Ishani said. “We followed the results of the participants using their electronic health records. This study was non-intrusive, cost-effective and inexpensive. We also managed to recruit more rural residents, about half of the participants, which is typical for this type of study. It usually has to rely on large academic medical centers.”

Researchers looked at more than 13,500 US soldiers at least 65 years old who received care from 4,120 primary care professionals at 500 clinics. Participants were predominantly male (97%), white veterans (77%), non-Hispanic veterans (93%), 55% urban. At the start of the study, mean systolic blood pressure (the highest number in a blood pressure reading) was 139 mm Hg. The participants were randomly divided into one of two groups: 1) hydrochlorothiazide at 25 or 50 mg/day, or 2) an equivalent dose of 12.5 or 25 mg/day chlorthalidone. The study examined the rates of heart attack, stroke, heart attack or non-cancer death after about 2.5 years.

Analysis of all study participants found:

• Heart disease and death rates were almost the same in the chlorthalidone group (9.4%) and the hydrochlorothiazide group (9.3%);

• In addition, there was no difference in secondary outcomes (heart attack, stroke, heart failure or other cardiovascular outcomes) between participants taking the two different drugs.

• However, in subgroup analysis, differences were found:

  • Among participants who had a history of heart attack or stroke, those taking Clotalidone had an average 27% lower risk of heart disease and death.

  • Clotalidone worsened these outcomes by an average of 12 percent in participants without a history of heart attack or stroke.

“We were surprised by these results,” Ishani said. “We expected chlorthalidone to be more effective overall, but learning about these differences in patients with a history of cardiovascular disease could impact patient care. It’s good for people to talk to their healthcare professionals about which of these drugs is best for their individual needs.”

“More research is needed to further investigate these effects because we don’t know how they hold in the general population.”

The authors also noted that there was little statistical difference between participants with low potassium levels, for unadjusted heart rate risk, in the clotalidone (6%) group and the hydrochlorothiazide group (4.4%). There was also a tendency for more people with low potassium levels to be hospitalized in the chlorthalidone group (1.5%) compared with the hydrochlorothiazide group (1.1%). Further research is needed to determine whether these results are true differences or due to the way participants were recruited. It is also unclear how this applies to women or other populations.

Co-authors William C. Cushman, MD; Sarah M. Leatherman, Ph.D. Robert A. Lew, Ph.D. Patricia Woods, MSN, RN; Peter A. Glassman, MBBS, M.Sc.; Addison A. Taylor, MD; Cynthia Howe, MPH; Alison Clint, MS; Grant D. Huang, MPH, PhD, Mary T.

The study was funded by the VA’s Cooperative Research Program.

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