There were no significant differences in cardiovascular outcomes, including death, between the use of hydrochlorothiazide or chlorthalidone among older adults with hypertension, according to new research presented at the American Heart Association (AHA) 2022 Scientific Sessions.
Presented by Areef Ishani, MD, results from The Diuretic Comparison Project, which enrolled more than 13,000 participants with hypertension, suggest that there was no difference in cardiovascular outcomes or non-cancer deaths with the use of chlorthalidone over hydrochlorothiazide, but the researchers noted that subgroup analyzes suggested that chlorthalidone might provide benefits in people with a history of cardiovascular disease or stroke.
“We were surprised by these results,” Ishani, the director of the Integrated Care Community of Primary Care and Specialty Care in Minneapolis and the director of the VA Midwest Healthcare Network in Minneapolis, said in a communicated “We expected chlorthalidone to be more effective overall, but knowing these differences in patients with a history of cardiovascular disease can affect patient care. It’s best for people to talk to their doctors about which of these drugs is best.” for their individual needs.”
There is a paradox in the management of hypertension in the US. Although recent guidelines recommend chlorthalidone over other diuretics for the treatment of hypertension, real-world data suggest that hydrochlorothiazide remains the preferred choice for most physicians prescribing diuretics for the treatment of hypertension. Launched in 2016, the Diuretic Comparison Project was created to enroll 13,500 veterans with hypertension identified through national Veterans Affairs (VA) and non-VA databases with 3-year follow-up to better understand how diuretic choice could influence clinical outcomes. .
In an open-label study, patients were randomized to maintain the current dose of hydrochlorothiazide or to be converted to an equipotent dose of chlorthalidone. To be included in the study, patients had to be at least 65 years old, be receiving AV hydrochlorothiazide, and have a most recent systolic blood pressure reading of 120 mmHg or higher. The primary outcome of interest for the study was a composite of major adverse cardiovascular events including stroke, myocardial infarction, heart failure hospitalization, urgent coronary revascularization, and non-cancer death.
A total of 16,595 people from 500 medical centers in the United States underwent participation control. Of these, 13,523 were randomized, with 6,756 randomized to chlorthalidone and 6,767 randomized to hydrochlorothiazide. The general study population had a mean systolic blood pressure of 139 mmHg, was 97% male, 77% white, 93% non-Hispanic, and 55% reported living in urban areas. The mean duration of study follow-up was 2.4 years.
After analysis, the results indicated that a primary outcome event occurred in 10.4% of those receiving chlorthalidone and 10.0% of those receiving hydrochlorothiazide (HR, 1.04). [95% CI, 0.94-1.16]; P=.04). Further analysis indicated that the rate of cardiovascular disease or death was 9.4% with chlorthalidone and 9.3% with hydrochlorothiazide. The researchers noted that no significant differences were observed for the incidence of myocardial infarction, stroke, heart failure, or other cardiovascular outcomes observed in their analyses.
However, the researchers noted that notable differences were observed in subgroup analyses. Specifically, those with a history of myocardial infarction or stroke who received chlorthalidone experienced a 27% relative risk reduction of all-cause mortality and cardiovascular disease compared with hydrochlorothiazide, but chlorthalidone appeared to worsen these same outcomes in those no history of myocardial infarction or stroke. Additional analyzes revealed that there were increased rates of hospitalization for hypokalemia among those randomized to chlorthalidone (1.5%) compared with those randomized to hydrochlorothiazide (1.1%).
“We were surprised by these results,” Ishani said. “We expected chlorthalidone to be more effective overall, but knowing these differences in patients with a history of cardiovascular disease can affect patient care. It’s best for people to talk to their doctors about which of these drugs is best.” for your individual needs.
This study, “Chlorthalidone versus hydrochlorothiazide for the prevention of cardiovascular events in patients with hypertension: the Diuretic Comparison Project (DCP),” was presented at AHA 22.