Chicago—In unexpected results of a new study, two common diuretics used to control BP—chlorthalidone and hydrochlorothiazide—showed no differences in outcomes for cardiovascular events, including death.
Conventional wisdom for many prescribers is that chlorthalidone is more effective. Guidelines usually recommend chlorthalidone to treat hypertension, although many providers opt for hydrochlorothiazide.
The Diuretic Comparison Project was presented at the American Heart Association’s Scientific Session 2022 in Chicago and published in The New England Journal of Medicine. Using a cohort of U.S. veterans with hypertension, the study compared how the two commonly prescribed BP-lowering medications prevent cardiovascular events. The pragmatic trial allowed participants and healthcare professionals to know which medication was being prescribed and to administer the medication in a real-world setting.
The results are especially significant since nearly half of U.S. adults have high BP, a leading cause of heart disease, according to the American Heart Association’s Heart Disease and Stroke Statistics 2022 Update. Thiazide diuretics, such as chlorthalidone and hydrochlorothiazide, have been prescribed for more than 50 years as first-line treatments for high BP.
The researchers sought to evaluate the safety and efficacy of hydrochlorothiazide and chlorthalidone in improving cardiovascular outcomes among patients with hypertension, noting a dearth of information from previous studies on their comparison.
The study included 13,523 patients recruited from 72 Veteran’s Affairs (VA) medical centers, which involved 537 clinics in all 50 states. Among the patients, 45% of individuals resided in rural areas and approximately 15% were black or African American. Because this was the VA population, there were few women (3%) in the study.
The participants were aged older than 65 years, prescribed 25 mg or 50 mg of hydrochlorothiazide by the VA, and had a mean baseline systolic blood pressure of 139 mmHg. The researchers divided patients into one of two groups, either hydrochlorothiazide at 25 mg/day or 50 mg/day, or an equivalent dose of 12.5 mg/day or 25 mg/day of chlorthalidone. The study examined rates of heart attack, stroke, heart failure, and noncancer death after a follow up of 2.4 years.
No differences were found in blood pressure over time or in the primary outcome of cardiovascular events or noncancer death. The authors noted a slight increase in the number of patients found to have low potassium in the chlorthalidone group—6.0% versus 4.4%.
This study found no additional cardiovascular benefit for treatment with chlorthalidone. Patients who received chlorthalidone did not have a lower occurrence of major cardiovascular outcome events or noncancer-related deaths than patients who received hydrochlorothiazide.
Subgroup analysis suggests a difference in the primary outcome by the presence or absence of prior stroke or heart attack. Among the small group of patients who had a history of heart attack or stroke, those taking chlorthalidone reduced the risks of heart disease and death by an average of 27%. The researchers called for further studies to understand the findings.
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