Consider Chlorthalidone as Diuretic of Choice for Hypertension

Internal Medicine World ReportJuly 2007
Volume 0
Issue 0

Our Expert Proposes Not Prescribing HCTZ

By Wayne Kuznar

CHICAGO—Although diuretics are recommended in national guidelines as a first-line pharmacologic option for the treatment of hypertension, their appropriate use in practice is less clear. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) recommends thiazide-type diuretics as an initial drug choice, but it does not advocate one over another.

At the American Society of Hypertension annual meeting, William J. Elliott, MD, PhD, made a case for using kidney function to guide the choice of diuretic. He presented evidence that chlorthalidone (Thalitone, Hygroton) should be considered over hydrochlorothiazide (HCTZ) as the thiazide diuretic of choice.

Data strongly support diuretics, not only for lowering blood pressure but also for improving clinical outcomes in patients with hypertension, said Dr Elliott, professor of preventive medicine, internal medicine and pharmacology, Rush Medical College, Chicago.

"Diuretics are particularly useful for hypertensives with chronic kidney disease (usually loop diuretics); diabetes, because their blood pressure target is lower, and you'll seldom get there without a diuretic; and a high risk of heart failure, because diuretics are the best medicines at preventing heart failure," he said.

In meta-analyses of clinical trials conducted in patients with hypertension, diuretics were associated with a 14% relative reduction in the risk of stroke and a 16% relative reduction in the risk of incident heart failure compared with angiotensin-converting-enzyme inhibitors. When compared with calcium antagonists, diuretics reduced the risk of incident heart failure by 41%.

The question then becomes: Which diuretic for which patient?

"If the estimated glomerular filtration rate [eGFR] is less than 40 mL/min/1.73 m2, we typically use a loop diuretic," said Dr Elliott. If using furosemide, it should be dosed according to the patient's age and blood urea nitrogen (BUN) as follows: (age + BUN)/2 = dose in mg (given twice daily). Bumetanide (Bumex) should be dosed twice daily and torsemide (Demadex) once in the morning.

If eGFR is >40 mL/min/1.73 m2, he prefers chlorthalidone, 12.5 or 25.0 mg once daily in the morning. Other options are HCTZ as part of a combination or ethacrynic acid if patients are allergic or hypersensitive to "sulfas" or other loop diuretics.

Chlorthalidone has an edge over HCTZ, although the 2 agents have been compared directly in only 1 morbidity and mortality study, the Multiple Risk Factor Intervention Trial (MRFIT).


Chlorthalidone is the more potent antihypertensive. In a recent study, 8 weeks of treatment with chlorthalidone, started at 12.5 mg/day and titrated to 25 mg/day, was associated with significant reductions in ambulatory systolic blood pressure (SBP), nighttime SBP, and office SBP compared with HCTZ started at 25 mg/day and titrated to 50 mg/day (. 2006; 47:352-358).

"We have taken people on hydrochlorothiazide on the very same dose, given them chlorthalidone, and have seen about a 12-mm Hg drop in systolic pressure, with no particular troubles with potassium," said Dr Elliott.

In his clinic, 94% of cases of so-called resistant hypertension are related to suboptimal medication regimens. "In 70% of these cases, a change in diuretic worked. We typically changed the ineffective hydrochlorothiazide for the same dose of chlorthalidone and saw substantial reductions in blood pressure," he said.


In MRFIT, which included 12,866 high-risk men aged 35 to 57 years, a favorable mortality trend was evident at 10.5 years of follow-up in the group receiving special intervention versus usual care (. 1990;82:1616-1628). One of the contributing factors, noted the investigators, was a change in the diuretic treatment protocol from HCTZ to chlorthalidone at 5 years after randomization.


  • Current data strongly support diuretics as first-line therapy for hypertension.
  • HCTZ is the predominant diuretic prescribed initially.
  • Chlorthalidone is the most potent thiazide-type diuretic. One expert suggests using it as the initial drug of choice instead of HCTZ.

In the 6 clinics that participated in MRFIT in which chlorthalidone was used predominantly, coronary heart disease (CHD) mortality and all-cause mortality were 58% and 41% lower, respectively, in the intervention group versus the usual-care group. In contrast, CHD mortality and all-cause mortality were higher in the intervention group in the 9 clinics in which HCTZ was the predominant diuretic prescribed initially.

"I have proposed, at least in our medical center, adding HCTZ to the 'do not use' abbreviation list, because I believe that if we made doctors write out hydrochlorothiazide, they would soon thereafter learn how to spell c-h-l-o-r-th-a-l-i-d-o-n-e, which is the right way to treat most patients' blood pressure," said Dr Elliott.

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