Key result
Fixed-dose losartan plus HCTZ lowers clinic and 24-hour ambulatory BP more than HCTZ monotherapy.
Why the study?
The comparative antihypertensive effects of two fixed-dose combinations of losartan/hydrochlorothiazide versus hydrochlorothiazide monotherapy in ambulatory systolic hypertension were not fully characterized.
Does a fixed-dose combination of losartan and hydrochlorothiazide reduce clinic and ambulatory blood pressure in patients with systolic hypertension compared to hydrochlorothiazide monotherapy?
RCT (n=120)
randomized
Does a fixed-dose combination of losartan and hydrochlorothiazide reduce clinic and ambulatory blood pressure in patients with systolic hypertension compared to hydrochlorothiazide monotherapy?
Fixed-dose combinations of losartan and hydrochlorothiazide provide significantly greater ambulatory and clinic blood pressure reductions compared to hydrochlorothiazide monotherapy in patients with systolic hypertension.
Answers are grounded in this paper and cite their sources.
Supports fixed-dose losartan-hydrochlorothiazide over hydrochlorothiazide monotherapy for systolic hypertension; confirms ARB-diuretic combination superiority in RCTs.
The objective of the present study was to assess the BP-lowering effects of two fixed-dose combinations of losartan/hydrochlorothiazide (L/HCTZ) compared with hydrochlorothiazide (HCTZ) monotherapy. For this purpose, 120 patients with clinic systolic BP between 160 and 220 mm Hg and mean ambulatory daytime sytolic BP ≥ 135 mm Hg were randomized to receive L 50 mg (n=60) or HCTZ 12.5 mg (n=60) for 6 weeks. Both groups were respectively force-titrated to L 50/HCTZ 12.5 mg or sham-titrated to HCTZ 12.5 mg for 6 weeks. Patients were then force-titrated to L100/ HCTZ 25 mg and HCTZ 25 mg for the remaining 6 weeks of the study. Clinic and 24-hour ambulatory BP were measured at baseline and after each 6-week treatment period. After 6 weeks, L 50 mg and HCTZ 12.5 mg induced significant and similar decreases in clinic BP and during each period of the 24-hour ambulatory BP monitoring (ABPM). At weeks 12 and 18, the combinations of L 50/HCTZ 12.5 mg and L 100/HCTZ 25 mg provided significant respective additional decreases in ambulatory systolic and diastolic BP suggesting a clear dose-response relationship. In contrast, the L 100/HCTZ 25 mg combination did not provide additional decreases vs L 50/HCTZ 12.5 mg in clinic BP. For the HCTZ-treated group, ambulatory and clinic BP decrements were statistically significant with the use of HCTZ 12.5 mg and HCTZ 25 mg. However, increasing the dosage of HCTZ 12,5 mg to 25 mg induced marginal and non-significant additional BP decrements. Between-treatment group comparisons demonstrated that both combinations of L/HCTZ provided significantly greater BP decreases than monotherapies with HCTZ during each period of the 24-hour interval and in clinic BP. In conclusion, the results of the present study demonstrated the efficacy of a combination therapy with L and HCTZ in decreasing ambulatory blood pressures with a clear dose response relationship in patients with systolic hypertension. In addition, the results provided further evidence for the use of ABPM when assessing the efficacy of antihypertensive agents given alone or in combination.
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Y LACOURCIERE (2003) conducted an RCT in ambulatory systolic hypertension (n=120). Losartan and hydrochlorothiazide fixed-dose combination vs. Hydrochlorothiazide monotherapy (12.5 mg titrated to 25 mg) was evaluated on Clinic and 24-hour ambulatory blood pressure. Fixed-dose combinations of losartan and hydrochlorothiazide provided significantly greater decreases in clinic and 24-hour ambulatory blood pressure than hydrochlorothiazide monotherapy.
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