Presented by Areef Ishani, MD, the results of The Diuretic Comparison Project, which included more than 13,000 participants with hypertension, suggested that there was no difference in cardiovascular outcomes or noncancer deaths with the use of chlorthalidone versus hydrochlorothiazide, but the researchers pointed out that subgroup analyzes suggested benefit in people with a history of cardiovascular disease or stroke. “We were surprised by these results,” Ishani, the director of Minneapolis’ comprehensive primary care and specialty care community and director of the VA Midwest Health Care Network in Minneapolis, said in a statement. “We expected chlorthalidone to be more effective overall, however, learning these differences in patients who have a history of CVD may impact patient care. It’s best for people to talk to their health care 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 clinicians prescribing diuretics for the management of hypertension. The Diuretic Comparison Project, which began in 2016, was designed to enroll 13,500 veterans with hypertension identified using national Veterans Affairs (VA) and non-VA databases with 3-year follow-up to better understand how diuretic choice may affect the clinical results. . In an open-label study, patients were randomized to remain on their current dose of hydrochlorothiazide or switched to an equivalent dose of chlorthalidone. To be included in the study, patients had to be at least 65 years old, receive hydrochlorothiazide from the VA, 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, hospitalization for heart failure, emergency coronary revascularization, and noncancer death. A total of 16,595 people from 500 US medical centers were screened for participation. Of these, 13,523 were randomized, with 6756 randomized to chlorthalidone and 6767 randomized to hydrochlorothiazide. The overall study population had a mean baseline systolic blood pressure of 139 mmHg, was 97% male, 77% White, 93% non-Hispanic, and 55% reported living in urban areas. The median follow-up for the study was 2.4 years. After analysis, the results showed that a primary outcome event occurred among 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 showed that the rate of cardiovascular disease or death was 9.4% with chlorthalidone and 9.3% with hydrochlorothiazide. The researchers noted that there were no significant differences in the incidence of myocardial infarction, stroke, heart failure, or other cardiovascular outcomes seen in their analyses. However, the researchers noted that significant differences were observed in subgroup analyses. Specifically, those with a history of myocardial infarction or stroke who received chlorthalidone had a 27% relative reduction in the risk of all-cause mortality and cardiovascular disease compared with hydrochlorothiazide, but chlorthalidone appeared to exacerbate these same effects in those without a history of myocardial infarction. myocardial or Cerebral. 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, however, learning these differences in patients who have a history of CVD may impact patient care. It is best for people to talk to their health care doctors about which of these drugs is best for their individual needs. This study, “Chlorothalidone compared with hydrochlorothiazide for the prevention of cardiovascular events in hypertensive patients: The Diuretic Comparison Project (DCP),” was presented at AHA 22.
