Low-dose chlorthalidone is significantly better at reducing blood pressure over a 24-hour period than is the most commonly prescribed formulation of hydrochlorothiazide for essential hypertension, findings from a randomized, controlled trial published Jan. 25 suggest.
Standard HCTZ at 12.5 mg was seen reducing blood pressure during daytime or office hours, resulting in undetected or masked hypertension during nighttime and early-morning hours, investigators found.
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However, both 6.25 mg chlorthalidone and an extended-release preparation of 12.5 mg HCTZ were shown to be effective at sustaining a smooth, 24-hour control as measured by ambulatory blood pressure monitoring.
For their research, Dr. Anil K. Pareek of Ipca Laboratories in Mumbai, India, and his colleagues randomized 54 patients aged 65 years and younger with stage 1 hypertension and no comorbidities to chlorthalidone, 6.25 mg (16 patients); HCTZ 12.5 mg (18); or HCTZ-controlled release 12.5 mg (20) for 12 weeks.
For the cohort as a whole, patients’ mean in-office blood pressure was 149/93 mm Hg. At both 4 and 12 weeks, all three study arms saw significant reductions in office BP (P less than .01).
However, only patients treated with chlorthalidone or HCTZ-CR saw statistically significant reductions in ambulatory diastolic and systolic blood pressure at both time points, while the standard HCTZ group did not see statistically significant changes. At 12 weeks, patients treated with chlorthalidone or HCTZ-CR achieved reductions of 11.1/7.8 mm Hg, and 10.3/8.2 mm Hg, respectively, while those in the standard HCTZ arm saw drops of 6.0/4.2 mm Hg (J Am Coll Cardiol. 2016 Jan 25;67:379-89).
Also at 12 weeks, the chlorthalidone and HCTZ-CR groups had mean nocturnal systolic pressure decreases of 10.2 and 12.7 mm/Hg, respectively, while those receiving standard HCTZ saw nighttime SBP reduced by mean 4.9 mm Hg.
Low potassium was seen in 10% (n = 2) of patients taking HCTZ-CR, 5.6% of patients on standard HCTZ, and 6.3% (n = 1) of patients on chlorthalidone.
Dr. Pareek and his colleagues noted that chlorthalidone possesses a distinct pharmacokinetic profile from HCTZ, with a higher potency that allows it to be used as monotherapy in smaller doses and has “a wider volume of distribution, with partitioning into red blood cells” that may be responsible for its longer duration of action.
Dr. Pareek and his colleagues wrote that previous studies have shown an overestimation of the response to standard HCTZ, based on office blood pressure measurements alone.
“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,” the researchers wrote. “With HCTZ therapy, sustained hypertension merely will be converted into masked hypertension.”
Low-dose chlorthalidone can be used as monotherapy in treating essential hypertension, Dr. Pareek and his colleagues concluded, whereas standard low-dose HCTZ should no longer be considered an acceptable option.
The investigators noted as a limitation of their study its small size.
Ipca Laboratories, a manufacturer of chlorthalidone, sponsored the study, whose lead author and two coauthors are also employees of Ipca.