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.
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?
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.
p-value: p=<0.01
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).
“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.”
Pareek et al. (Mon,) conducted a 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.