#61 Is Hydrochlorothiazide the Best Thiazide Diuretic for Hypertension?
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- Chlorthalidone reduces systolic BP better than HCTZ at equivalent doses with similar effects on potassium:1,2
- Chlorthalidone 25 mg, compared to HCTZ 50 mg, provided superior BP reduction overall (12 versus 7 mmHg on 24-hr monitor) and at nighttime (13 versus 6 mmHg).3
- Retrospective (and thus not considered definitive) analysis of the MRFIT trial: Chlorthalidone-based regimen reduced mortality versus HCTZ-based regimen (HR: 0.79 [95% CI: 0.68 to 0.92]; P=0.0016).4
- Retrospective cohort study of 29,873 patients from Ontario found no difference in cardiovascular outcomes but increased risk of electrolyte abnormalities with chlorthalidone.5
- Large trials using chlorthalidone (like ALLHAT6 and SHEP7) have demonstrated reductions in cardiovascular endpoints whereas HCTZ evidence is less robust.
- Network meta-analysis of nine randomized controlled trials found chorthalidone associated with fewer cardiovascular events than hydrochlorothiazide (Relative risk~0.8).8 However, these were indirect comparisons.
- Other indirect comparisons with thiazide diuretics (not just hydrochlorothiazide) have found either no difference in cardiovascular outcomes9 or, in more recent studies, reduced cardiovascular events with chlorthalidone/indapamide.10,11
- Thiazide diuretics are first-line for hypertensive patients without compelling indications for an alternate drug.12-14
- Meta-analysis15 (19 trials): found 24-hour BP with 12.5-25 mg doses of HCTZ compared to other antihypertensive drugs:
- Systolic 4.5-6.2 mmHg and diastolic 2.9-6.7mmHg higher.
- Chlorthalidone has a longer half-life than HCTZ (50-60 versus 9-10 hours), which may explain the superior BP control, especially at nightime.16
- HCTZ’s advantage is availability in many combination preparations which may improve adherence.17
- Indapamide is another thiazide-like diuretic with good evidence for reduction in cardiovascular endpoints as first18 or second-line antihypertensive.19