Ambulatory blood pressure lowering efficacy of hydrochlorothiazide inferior to other drug classes


Investigators question whether the thiazide diuretic, hydrochlorothiazide, should be used as commonly as it is for treating hypertension, according to a report published in a recent edition of the Journal of the American College of Cardiology.

Key Points

Investigators question whether the thiazide diuretic, hydrochlorothiazide (HCTZ), should be used as commonly as it is for treating hypertension, according to a report published in a recent edition of the Journal of the American College of Cardiology.

In 2008, it was estimated that more than 130 million prescriptions for HCTZ (mainly 12.5- to 25-mg daily doses and including combination antihypertensive products) were written; making it the most commonly prescribed antihypertensive medication in the United States.

"The antihypertensive efficacy of HCTZ in its daily dose of 12.5 to 25 mg as measured in head-to-head studies by ambulatory BP measurement is consistently inferior to that of all other drug classes," remarked the investigators in their recent publication. They further stressed, "Because outcome data at this dose are lacking, HCTZ is an inappropriate first-line drug for the treatment of hypertension."

Upon meta-analysis, decreases in 24-hour systolic ABP with HCTZ 12.5 to 25 mg daily were found to be only 6.53 mmHg (95% CI, 5.32–7.74 mmHg). Twenty-four-hour diastolic ABP control was found to be little better (4.51 mmHg, 95% CI: 3.06–5.96 mmHg). Moreover, while no significant difference in 24-hour systolic or diastolic ABP control was seen between the 12.5- and 25-mg daily doses (P>.15 for systolic and diastolic ABPs), the 50-mg-per-day dose was found to reduce systolic ABP by 12 mmHg more than the 25-mg dose (P=.04).

The investigators further revealed that the 24-hour ABP reductions observed with HCTZ 12.5 to 25 mg daily were consistently less than that of other conventional antihypertensive medications including angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, beta-blockers, and calcium channel blockers (range of mean differences in 24-hour systolic ABP of 4.45 to 6.19 and diastolic ABP of 2.89 to 6.71; P<.02 for all comparisons of HCTZ vs other antihypertensive agents).

Of note, the meta-analysis reported that ABP reductions seen with the 50-mg HCTZ dose appeared comparable to that of other agents. The investigators, however, argued against the preferential use of this higher dose by emphasizing, "...all biochemical adverse effects such as hypokalemia, hyponatremia, hyperuricemia, insulin resistance, and visceral fat accumulation are dose dependent and become clinically more significant with daily doses exceeding 25 mg."

In the paper's discussion, investigators were quick to point out that current evidence supporting the hypothesis that the lower doses of HCTZ positively affect more important terminal outcomes is lacking; reminding readers that available terminal outcome trials were completed using higher doses of HCTZ or with other thiazide diuretics (ie, chlorthalidone or indapamide).

The investigators concluded their paper by recommending, "Because of such paltry antihypertensive efficacy and the lack of outcome data at these doses, physicians should refrain from prescribing HCTZ as initial antihypertensive therapy."


Messerli FH, Makani H, Benjo A, Romero J, Alviar C, Bangalore S. Antihypertensive efficacy of hydrochlorothiazide as evaluated by ambulatory blood pressure monitoring. A meta-analysis of randomized trials. J Am Coll Cardiol. 2011;57(5):590–600.

Drug Topics. 2008 Top 200 Generic Drugs By Total Prescriptions. Available at: Accessed January 30, 2011.

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