Key result
Adding hydrochlorothiazide to losartan lowers systolic blood pressure by ~12 mm Hg and ameliorates proteinuria.
Why the study?
The comparative renoprotective and blood pressure-lowering effects of combination losartan-low-dose hydrochlorothiazide versus losartan alone in hypertensive stage 3 CKD patients were unclear.
Does combination therapy with losartan 100 mg and hydrochlorothiazide 12.5 mg daily reduce blood pressure and proteinuria compared to losartan 100 mg daily in hypertensive patients with stage 3 CKD?
RCT (n=60)
Open-label
randomized
No
Does combination therapy with losartan 100 mg and hydrochlorothiazide 12.5 mg daily reduce blood pressure and proteinuria compared to losartan 100 mg daily in hypertensive patients with stage 3 CKD?
Adding low-dose hydrochlorothiazide to maximum-dose losartan provides superior blood pressure control and antiproteinuric effects compared to losartan alone in patients with stage 3 CKD.
Supports adding low-dose HCTZ to max-dose losartan in stage 3 CKD hypertension; extends RCT evidence for ARB-diuretic combination.
Study Objective. To compare the renoprotective and blood pressure‐lowering effects of combination losartan‐low‐dose hydrochlorothiazide with losartan alone in hypertensive patients with stage 3 chronic kidney disease (CKD). Design. Prospective, open‐label, randomized, controlled study. Setting. Outpatient clinic at a university‐affiliated hospital in Japan. Patients. Sixty adults (mean age 67 yrs) with stage 3 CKD who had been receiving losartan 50 mg/day and had not achieved their target blood pressure of 130/80 mm Hg. Intervention. Patients were randomly assigned to receive combination losartan 50 mg‐hydrochlorothiazide 12.5 mg/day in addition to losartan 50 mg/day (combination therapy group, 30 patients) or to receive losartan 100 mg/day (control group, 30 patients) over a 24‐week period. Measurements and Main Results. Efficacy was determined by monitoring clinical and laboratory parameters. Mean baseline systolic and diastolic blood pressures were 158/90 mm Hg in both groups; at 24 weeks of treatment, these blood pressures significantly decreased to 133/79 mm Hg in the combination therapy group compared with both baseline and the values in the control group (145/83 mm Hg). Although serum creatinine concentration increased and the estimated glomerular filtration rate decreased significantly in both groups, the urinary protein:creatinine ratio was significantly lower in the combination therapy group. With stratification of patients on the basis of whether they had diabetes mellitus, we found that the reduction in the urinary protein:creatinine ratio was more evident in the combination therapy group. No significant increase in the occurrence of adverse metabolic effects was noted in either group. Conclusion. In these hypertensive patients with stage 3 CKD, combination therapy with the maximum recommended daily dose of losartan of 100 mg and a low dose of hydrochlorothiazide of 12.5 mg ameliorated proteinuria and reduced blood pressure more effectively than treatment with losartan 100 mg alone, irrespective of whether the patients had diabetes.
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Abe et al. (2009) conducted an RCT in Hypertension with stage 3 chronic kidney disease (n=60). Losartan and hydrochlorothiazide vs. Losartan 100 mg/day was evaluated on Blood pressure and urinary protein:creatinine ratio. Combination therapy with losartan 100 mg and hydrochlorothiazide 12.5 mg reduced blood pressure more effectively than losartan 100 mg alone (133/79 vs 145/83 mm Hg) and ameliorated proteinuria.
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