Are Chlorthalidone and Hydrochlorothiazide Equivalent Blood‐Pressure‐Lowering Medications?

Abstract

W hile the majority of participants in clinical trials demonstrate the benefits of the thiazide-like diuretic, chlorthalidone (CTD), 1 hydrochlorothiazide (HCTZ) is prescribed more frequently in the United States. 2 Only one large outcome trial, the Multiple Risk Factor Intervention Trial (MRFIT), used both HCTZ and CTD, but no head-to-head comparisons were performed. In MRFIT, after about 5 years patients who received each diuretic as initial therapy were compared against the common "referred care" group. For patients who used CTD as initial therapy, there was a trend indicating lower mortality compared with those using HCTZ. Use of CTD declined after research studies using high doses suggested an increased risk of cardiovascular deaths and a high incidence of hypokalemia. 3 A recent review suggests that few differences exist between HCTZ and CTD-thus, they should be considered interchangeable. 4 These authors state, however, that there are differences in duration of action and pharmacology between the two agents. Based on these differences, we propose that the same dose of CTD when substituted for HCTZ may result in an additional systolic blood pressure (SBP) reduction and help achieve blood pressure (BP) goals in patients already receiving three or more medications. OBSERVATIONSA consecutive chart review from the Rush University Hypertension Center sought patients with the following inclusion criteria: age over 40 years, not at target BP for medical condition (<140/90 mm Hg and <130/80 mm Hg for those with kidney disease or diabetes), and on a stable antihypertensive regimen that included the same dose of HCTZ for at least 6 months. All patients underwent recording of two sitting BP readings. Nineteen of the 2000 charts (≈1%) screened met the inclusion criteria. The average of two seated BP readings from the initial visit and the follow-up (after the switch) were analyzed. Following the initial visit, patients were switched from HCTZ to CTD at the same daily dose without any further changes in their antihypertensive regimen. No patients received K + supplementation before or after the change. Laboratory data for serum K + and kidney function, as well as clinical data for BP and pulse rates, were recorded at follow-up visits. Patients were also asked about symptoms related to gout at each visit.Seventeen of the 19 patients were taking 25 mg of HCTZ at the index visit; two were taking a dose of 12.5 mg/d (Table). SBP values before and after the diuretic switch are shown for individual patients in the Figure. If two patients are eliminated, i.e., those with baseline SBPs of 220 mm Hg that decreased to 156 mm Hg and 194 mm Hg that decreased to 148 mm Hg, an overall median difference of 4 mm Hg instead of 7 mm Hg in SBP was noted (p=0.052). Six of the 19 who originally had uncontrolled hypertension achieved their individual BP targets after the change in medication. Serum K + levels from eight of the 19 patients were not significantly different (3.9±0.3 mEq/L on HCTZ vs. 4.0±0.4 mEq/L on CTD). Only one of these pat...

Comparative Antihypertensive Effects of Hydrochlorothiazide and Chlorthalidone on Ambulatory and Office Blood Pressure

“…In a small study of 19 patients with uncontrolled BP on stable doses of HCTZ for 6 months, substitution of chlorthalidone for HCTZ was found to reduce SBP an additional 4 to 7 mm Hg, which led to achieving goal BP in 6 of the 19 patients. 24 The trend observed with the 24-hour mean SBP in our study appeared to result from differences in the nighttime mean SBP, a finding which may have a pharmacokinetic basis. Chlorthalidone has a much longer elimination half-life (24 to 55 hours) than HCTZ (2.5 hours), 10 a property suggested to result in more sustained BP reduction over 24 hours.…”

Hydrochlorothiazide Versus Chlorthalidone in the Management of Hypertension

“…8 -10 Some experts still support its use in current practice, 11,12 yet HCTZ is much more commonly prescribed today. 13 This article will address the debate surrounding the relative efficacies of chlorthalidone and HCTZ in the treatment of hypertension.…”

Resistant Hypertension

“…A recent trial comparing hydrochlorothiazide 50 mg and chlorthalidone 25 mg daily demonstrated that the latter provided greater ambulatory BP reduction, with the largest difference occurring overnight (59). Additionally, a small study of patients with resistant hypertension demonstrated that switching from the same dose of hydrochlorothiazide to chlorthalidone resulted in an additional 8 mm Hg drop in systolic BP and increased the number of subjects at goal (60). Unfortunately, chlorthalidone is not commonly available in fixed-dose combinations; therefore, its use will require separate prescriptions.…”