CHICAGO — Despite its superior efficacy, the diuretic chlorthalidone is being underutilized in patients with hypertension, according to Dr. William J. Elliot.
The reason may be as simple as the lack of a convenient abbreviation.
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 is hydrochlorothiazide.
Dr. Elliott, a preventive medicine professor at Chicago's Rush University Medical Center, suggests chlorthalidone has fallen out of favor because hydrochlorothiazide can be abbreviated as HCTZ, while there is no standard abbreviation for chlorthalidone.
“In my opinion, the reason that people are not using chlorthalidone—a better diuretic—is because it unfortunately has to be written out, all 14 letters of it, whereas doctors can get by using only four letters of hydrochlorothiazide,” Dr. Elliot said at a press briefing at the annual meeting of the America Society of Hypertension.
He 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, P = .054).
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 vs. 6.4 mm Hg for HCTZ.
In the Multiple Risk Factor Intervention Trial, patients given HCTZ by investigators 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 (Circulation 1990;82:1616–28). 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, while 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 in women.
“I submit that 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, as both drugs are generically available and can be found on the Wal-Mart $4 per month drug list, said Dr. Elliott, who disclosed possible conflicts of interest with Pfizer Inc., Novartis Pharmaceuticals Corp., AstraZeneca, Kos Pharmaceuticals Co., Abbott Laboratories, and KV Pharmaceutical.
Dr. Elliott recommends low-dose chlorthalidone 12.5 mg because of better efficacy and longer duration of action. He uses diuretics in hypertensive patients with chronic kidney disease, diabetes, or 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, Detroit, agreed with Dr. Elliott's recommendation to use chlorthalidone over HCTZ. “One of the things that would really help is if a pharmaceutical company would have the courage to break the trend of simply putting HCTZ with everything,” Dr. Flack said.
While HCTZ is part of several fixed-dose combination drugs, chlorthalidone is available in only three combination products: clonidine (Clorpres), reserpine (Regroton), and atenolol (Tenoretic), Dr. Elliott said.