Is Monotherapy With Low-Dose HCTZ Effective for Treatment of Hypertension?

Study Questions:

In patients with stage 1 essential hypertension, what is the antihypertensive efficacy of hydrochlorothiazide (HCTZ) 12.5 mg once daily, as assessed by 24-hour ambulatory blood pressure monitoring (ABPM), compared to low-dose (6.25 mg) chlorthalidone?


This was a double-blind, double-dummy, randomized, parallel group, comparative, multicenter trial conducted in Indian patients. Patients were randomized in a 1:1:1 ratio to receive chlorthalidone 6.25 mg tablets, or HCTZ-controlled release (CR) 12.5 mg tablets, or conventional HCTZ 12.5 mg tablets. The primary efficacy parameter was the change in mean 24-hour ambulatory systolic blood pressure (SBP) and diastolic blood pressure (DBP) from baseline to week 4 and week 12. Comparative efficacy evaluations were performed at baseline, week 4, and week 12 for 24-hour ABPM and at baseline, week 2, week 4, week 8, and week 12 for office BP measurements.


Fifty-four patients were randomized to receive either chlorthalidone 6.25 mg (n = 16), HCTZ-CR 12.5 mg (n = 20), or HCTZ 12.5 mg (n = 18). Patients treated with chlorthalidone and HCTZ-CR showed a significant reduction in 24-hour ambulatory SBP and DBP from baseline (p < 0.01). At weeks 4 and 12, this reduction was not statistically significant for patients treated with conventional HCTZ. At weeks 4 and 12, all three treatments showed a significant reduction in mean office SBP. At week 12, patients from the chlorthalidone and HCTZ-CR groups showed a significant reduction from baseline in ambulatory nighttime SBP and DBP; this change was not significant in patients treated with conventional HCTZ.


Although low-dose chlorthalidone 6.25 mg once daily significantly reduced mean 24-hour ABP, daytime BP, and nighttime BP, no significant reductions were seen with low-dose HCTZ.


This is a valuable study that corroborates findings from others and challenges contemporary and widespread practice about the efficacy of low-dose HCTZ as monotherapy for hypertension. The results of this small study (n = 54) need to be confirmed.

Clinical Topics: Prevention, Statins, Hypertension

Keywords: Antihypertensive Agents, Blood Pressure, Blood Pressure Monitoring, Ambulatory, Chlorthalidone, Hydrochlorothiazide, Hypertension, Primary Prevention, Vascular Diseases

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