Key result
Low-dose chlorthalidone 6.25 mg lowers 24-hour ambulatory blood pressure whereas HCTZ 12.5 mg does not.
Why the study?
Thiazide and thiazide-like diuretics are increasingly used at lower doses, but the comparative efficacy of low-dose chlorthalidone versus commonly prescribed low-dose HCTZ and extended-release HCTZ by ambulatory blood pressure monitoring was unknown.
Does chlorthalidone 6.25 mg daily improve 24-h ambulatory blood pressure compared to hydrochlorothiazide 12.5 mg daily in patients with stage 1 hypertension?
RCT (n=54)
Double-blind
randomized
Does chlorthalidone 6.25 mg daily improve 24-h ambulatory blood pressure compared to hydrochlorothiazide 12.5 mg daily in patients with stage 1 hypertension?
p-value: p=<0.01
Low-dose chlorthalidone (6.25 mg daily) provides sustained 24-hour blood pressure reduction, whereas low-dose hydrochlorothiazide (12.5 mg daily) fails to reduce 24-hour ambulatory BP and may cause masked hypertension.
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“Assessing the antihypertensive efficacy of HCTZ by [office] BP measurements only is deceptive and prone to lull physicians and patients into a false sense of security. With HCTZ therapy, sustained hypertension merely will be converted into masked hypertension.”
“The clear message is that a low dose of a long-acting diuretic therapy can have a meaningful impact on the management of hypertension and on CV outcomes.”
“The findings of this new study add very little of value to most practitioners in the United States, and I suspect many other countries as well. These investigators have studied very low doses of the diuretics hydrochlorothiazide and chlorthalidone that are not available for prescription in the United States.”
Supports preferring low-dose chlorthalidone over HCTZ for 24-h BP control in stage 1 hypertension; extends office BP data to ambulatory monitoring.
BACKGROUND: Thiazide and thiazide-like diuretic agents are being increasingly used at lower doses. Hydrochlorothiazide (HCTZ) in the 12.5-mg dose remains the most commonly prescribed antihypertensive agent in the United States. OBJECTIVES: This study compared chlorthalidone, 6.25 mg daily, with HCTZ, 12.5 mg daily, by 24-h ambulatory blood pressure (ABP) monitoring and evaluated efficacy. Because HCTZ has been perceived as a short-acting drug, a third comparison with an extended-release formulation (HCTZ-controlled release [CR]) was added. METHODS: This 12-week comparative, double-blind, outpatient study randomized 54 patients with stage 1 hypertension to receive either chlorthalidone, 6.25 mg, (n = 16); HCTZ 12.5 mg (n = 18); or HCTZ-CR 12.5 mg (n = 20). ABP monitoring was performed at baseline and after 4 and 12 weeks of therapy. RESULTS: All 3 treatments significantly (p < 0.01) lowered office BP at weeks 4 and 12 from baseline. At weeks 4 and 12, significant reductions in systolic and diastolic 24-h ambulatory and nighttime BP (p < 0.01) were observed with chlorthalidone but not with HCTZ. At weeks 4 (p = 0.015) and 12 (p = 0.020), nighttime systolic ABP was significantly lower in the chlorthalidone group than in the the HCTZ group. With HCTZ therapy, sustained hypertension was converted into masked hypertension. In contrast to the HCTZ group, the HCTZ-CR group also showed a significant (p < 0.01) reduction in 24-h ABP. All 3 treatments were generally safe and well tolerated. CONCLUSIONS: Treatment with low-dose chlorthalidone, 6.25 mg daily, significantly reduced mean 24-h ABP as well as daytime and nighttime BP. Due to its short duration of action, no significant 24-h ABP reduction was seen with HCTZ, 12.5 mg daily, which merely converted sustained hypertension into masked hypertension. Thus, low-dose chlorthalidone, 6.25 mg, could be used as monotherapy for treatment of essential hypertension, whereas low-dose HCTZ monotherapy is not an appropriate antihypertensive drug. (Comparative Evaluation of Safety and Efficacy of Hydrochlorothiazide CR with Hydrochlorothiazide and Chlorthalidone in Patients With Stage I Essential Hypertension; CTRI/2013/07/003793).
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Pareek et al. (2016) conducted an RCT in stage 1 hypertension (n=54). Chlorthalidone vs. Hydrochlorothiazide (HCTZ) 12.5 mg daily and HCTZ-controlled release (CR) 12.5 mg daily was evaluated on 24-h ambulatory blood pressure (ABP) (p=<0.01). Low-dose chlorthalidone (6.25 mg daily) significantly reduced 24-h ambulatory blood pressure (p<0.01), whereas HCTZ (12.5 mg daily) did not.
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