CHICAGO — The diuretic chlorthalidone is being underused in patients with hypertension, despite its superior efficacy—and the reason may be as simple as the lack of a convenient abbreviation for it, according to Dr. William J. Elliot.
Studies support the efficacy of chlorthalidone in reducing hypertension, yet the diuretic hydrochlorothiazide remains favored in clinical practice. One theory is that chlorthalidone is associated with more hypokalemia than hydrochlorothiazide.
But Dr. Elliott, a preventive medicine professor at Chicago's Rush University Medical Center, suggests chlorthalidone has fallen out of favor because, unlike hydrochlorothiazide, which is easily abbreviated as HCTZ, there is no standard abbreviation for chlorthalidone. “It has to be written out, all 14 letters of it,” he said at a press briefing at the annual meeting of the America Society of Hypertension.
Dr. Elliott cited several studies favoring chlorthalidone, including a recent blinded randomized head-to-head comparison (Hypertension 2006;47:352–8) that showed a greater reduction in 24-hour mean systolic blood pressure at 8 weeks in patients receiving chlorthalidone 25 mg/day, compared with those receiving HCTZ 50 mg/day (−12.4 mm Hg vs. −7.4 mm Hg, respectively). The greater reduction with chlorthalidone, at half the dose, was thought to be primarily because of its effect on nighttime mean systolic blood pressure, which fell 13.5 mm Hg for chlorthalidone, compared with 6.4 mm Hg for HCTZ.
In the Multiple Risk Factor Intervention Trial (Circulation 1990;82:1616–28), patients who received HCTZ had 44% more coronary heart disease and 16% more deaths after 5 years of follow-up, compared with control patients cared for in the community by primary care physicians. Conversely, there was 58% less coronary heart disease and 41% fewer deaths in patients treated with chlorthalidone, compared with referred-care controls, Dr. Elliott said.
More recently, the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial found fewer cardiovascular events with chlorthalidone than with an angiotensin-converting enzyme inhibitor, and the second Australian National Blood Pressure study found an inhibitor to be superior to HCTZ at reducing combined mortality and morbidity in men, but not women.
“We ought to be putting HCTZ on the list of 'do not use' abbreviations because it is an inferior product and ought to be replaced in general practice by chlorthalidone,” he said.
Cost is not a factor in the argument, because both drugs are generically available, said Dr. Elliott, who disclosed possible conflicts of interest with Pfizer Inc., Novartis Pharmaceuticals Corp., Astra-Zeneca, Kos Pharmaceuticals Co., Abbott Laboratories, and KV Pharmaceutical.
He recommends low-dose chlorthalidone 12.5 mg because of its better efficacy and longer duration of action. He uses diuretics in hypertensive patients with chronic kidney disease, diabetes mellitus, or at high risk of heart failure, but typically switches patients with severe late-stage kidney disease to loop diuretics taken twice daily.
Dr. John Flack, of Wayne State University, in Detroit, told reporters he agreed with Dr. Elliott's recommendation to use chlorthalidone over HCTZ. “It would help if a pharmaceutical company had the courage to break the trend of simply putting HCTZ with everything. They seem reluctant to do it.”
HCTZ is part of several fixed-dose combination drugs, but chlorthalidone is available in only three combination products: clonidine (Clorpres), reserpine (Regroton), and atenolol (Tenoretic), Dr. Elliott explained.