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(L/H group), and 15 patients received candesartan (8 mg/day)/amlodipine (5 mg/day) (C/A group) after 5 patients were withdrawn. After 4 months, L/H 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. L/H significantly reduced serum potassium, but within the normal range, and did not increase serum uric acid or serum triglyceride. With L/H, the percentage of patients who attained the BP goal in SBP was higher in elderly patients than in younger patients. As L/H 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.
Shimosawa
Tatsuo
T
Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Tokyo, Japan.
Gohchi
Kengo
K
Yatomi
Yutaka
Y
Fujita
Toshiro
T
D000368:Aged; D017311:Amlodipine / Q000009:adverse effects / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D044466:Asian People; D001562:Benzimidazoles / Q000009:adverse effects / Q000627:therapeutic use; D001713:Biphenyl Compounds; D004232:Diuretics / Q000008:administration & dosage* / Q000009:adverse effects; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D006852:Hydrochlorothiazide / Q000009:adverse effects / Q000627:therapeutic use; D006973:Hypertension / Q000188:drug therapy*; D007564:Japan; D019808:Losartan / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D013777:Tetrazoles / Q000009:adverse effects / Q000627:therapeutic use; D016896:Treatment Outcome
D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D004232:Diuretics; D013777:Tetrazoles; D006852:Hydrochlorothiazide; D017311:Amlodipine; D019808:Losartan; C081643:candesartan