Effectiveness of add-on low-dose diuretics in combination therapy for hypertension: Losartan/hydrochlorothiazide vs. candesartan/amlodipine

In guidelines, a combination therapy of two or more antihypertensives is recommended for treatment of hypertension where monotherapy is ineffective. Although diuretics or calcium channel blockers are commonly used as add-ons to angiotensin receptor blocker (ARB), the most effective and safe combination has not been established. In this randomized 4-month study, the efficacy and safety were compared between an ARB/diuretics (losartan/hydrochlorothiazide [HCTZ]) combination and the most prescribed combination, ARB/calcium channel blocker (candesartan/amlodipine) in hypertensive patients for whom 8 mg/day of candesartan proved ineffective. After 36 patients were recruited and allocated into two groups, changes in blood pressure (BP) and laboratory values were analyzed in 31 patients: 16 patients received losartan (50 mg/day)/HCTZ (12.5 mg/day) (L/H group), and 15 patients received candesartan (8 mg/day)/amiodipine (5 mg/day) (C/A group) after 5 patients were withdrawn. After 4 months, UH significantly (p<0.001) reduced mean systolic BP (SBP)/diastolic BP (DBP) from baseline 160/89 +/- 13/11 mmHg to 140/80 +/- 9/8 mmHg, and C/A reduced BP from 161/90 +/- 10/11 mmHg to 141/79 +/- 10/7 mmHg. The efficacy in reducing BP was similar between the two combination therapies. UH significantly reduced serum potassium, but within the normal range, and did not increase serum uric acid or serum triglyceride. With UH, the percentage of patients who attained the BID goal in SBP was higher in elderly patients than in younger patients. As UH is more cost-effective than candesartan/amlodipine and has fewer adverse effects on uric acid and other metabolic parameters than diuretic monotherapy, it is concluded to be useful for the management of hypertension.