Is very low dose hydrochlorothiazide combined with candesartan effective in uncontrolled hypertensive patients?

BACKGROUND: It is controversial whether the combination of very low dose hydrochlorothiazide (HCTZ) and an angiotensin receptor blocker (ARB) is effective in lowering blood pressure (BP). OBJECTIVES: The aim of this study was to evaluate the antihypertensive effect and the safety of an ARB and a very low dose of HCTZ in hypertensive patients. METHODS: This is an observational study. We examined 41 hypertensive patients who were treated with candesartan or another ARB at a standard dose but whose home BP was still greater than or equal to 135/85 mmHg. No patients were taking diuretics at baseline. Clinic and ambulatory BP (ABP) measurement and blood/urine analyses were performed at baseline and in the 2nd to 3rd month after treatment. All patients were either maintained at or switched to 8 mg candesartan, and then 6.25 mg HCTZ was added. Other concomitant drugs were not changed throughout the study period. RESULTS: A total of 41 individuals (age 62.7±12.7 years, 61% male) completed the protocol. The add-on treatment of HCTZ significantly lowered clinic and ABPs for both systolic and diastolic BP. The BP reduction was particularly pronounced in sleep BP. In addition, the rate of nondippers decreased from 48.8 to 36.6%, but the rates of dippers (39.0-43.9%) and extreme-dippers (12.2-19.5%) increased. Serum uric acid increased significantly, but the other metabolic measures were not changed by the combination therapy. CONCLUSION: Adding a very low dose of HCTZ (6.25 mg) to an ARB was very effective in lowering clinic and ABP, particularly for night-time BP.