Knowledge
- Hypertensive older adults have a similar risk of serious adverse cardiovascular events, regardless of whether they are treated with doses of chlortalidone or hydrochlorothiazide commonly used in clinical practice.
Why this matters
- Early studies suggested that chlortalidone is superior, and the guidelines favorably recommend this drug.
Study design
- US randomized controlled phase III study with 13,523 hypertensive veterans 65  and older; years receiving hydrochlorothiazide (25 or 50 mg/day, study Diuretic Comparison Project).
- Randomization: continuation of hydrochlorothiazide vs.Switching to chlortalidone (12,5 or 25 mg/day)
- Primary endpoint: serious adverse cardiovascular events (consisting of nonfatal myocardial infarction, stroke, hospitalization due to heart failure, urgent coronary revascularization due to unstable angina and non-cancer death)
- Funding: Veterans Affairs Cooperative Studies Program
Key results
- In both the chlortalidone and hydrochlorothiazide groups, mean systolic blood pressure at baseline was 139 mmHg and remained stable during follow-up.
- During a median follow-up of 2,4 years serious adverse cardiovascular events occurred in 10,4 % in the chlortalidone group and 10,0 % in the hydrochlorothiazide group (HR: 1.04; p = 0.45).
- The groups were also statistically similar in terms of frequency of occurrence of each component of the primary outcome.
- Subgroup analyses indicated a possible superiority of chlortalidone over hydrochlorothiazide in patients with myocardial infarction or stroke (HR: 0.73).
- In the chlortalidone group, hypokalemia developed more frequently (6,0 % vs.4,4 %; p <0.001).
Expert comment
- In a Editorial, Julie R. Ingelfinger, MD, Harvard Medical School and Massachusetts General Hospital writes: «These results are not surprising and may not change clinical practice. … Currently, doctors generally prefer the use of hydrochlorothiazide in their patients; these head-to-head results suggest similar benefits with both agents with respect to the primary outcome, but without likely impetus for change.»
Restrictions
- The rate of treatment change was higher in the chlortalidone group.
- The incidence of the primary outcome was lower than expected.
- The study was conducted prior to the planned median follow-up of 3 years.
- Results may differ when using different doses.
- The generalizability to younger and female patients is uncertain.
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