Fixed-dose Combination Of Losartan Research Articles

Fixed-dose combination of losartan and hydrochlorothiazide significantly improves endothelial function in uncontrolled hypertension by low-dose amlodipine: a randomized study.

Flow-mediated dilation (FMD) and nitroglycerin-mediated dilation (NMD) in the brachial artery are well-known indices for evaluating endothelial function (ECF). The blood pressure-lowering effects of the combination of losartan (ARB) and low-dose hydrochlorothiazide (H: ARB-H; ARB, 50 mg and H, 12.5 mg) are useful. The aim of the present study was to examine whether the combination of losartan and low-dose hydrochlorothiazide could improve ECF. To investigate the effect of ARB-H on ECF in patients with uncontrolled hypertension despite the use of amlodipine (2.5 mg daily), we performed a randomized controlled open-labeled study by using the envelope method and assigned 42 patients to either a control (CTRL) group or an ARB-H combination group, both of which received amlodipine 2.5 mg daily during the treatment period. In addition, both the CTRL (n=21, 69±7 years old) and ARB-H groups (n=21, 69±7 years old) received additional behavioral modification. Before and after 8 weeks of therapy, FMD and NMD were measured in both groups using novel FMD equipment (UNEXEF18G). Although baseline FMD was not different between the two groups, post-therapy FMD increased in the ARB-H group (2.97±1.56 to 3.95±1.86%, p<0.05) but did not change significantly in the CTRL group (2.95±1.43 to 3.11±1.27%, NS). No significant change was seen in NMD when comparing baseline and post-therapy values in either group. No treatment complications were observed. A fixed-dose combination of losartan and hydrochlorothiazide enhances ECF, suggesting that this combination might have both anti-hypertensive and anti-atherosclerotic effects in patients with hypertension.

Long-term Antihypertensive Efficacy of Losartan/Hydrochlorothiazide Combination Therapy on Home Blood Pressure Control

Angiotensin receptor blocker (ARB)/hydrochlorothiazide (HCTZ) combination therapy has been shown to produce a prompt reduction in clinic blood pressure (BP) without serious adverse effects; however, long-term antihypertensive efficacy on home BP has not been fully investigated. In this open-label multicenter observational study, a total of 151 hypertensive patients uncontrolled with antihypertensive regimens including standard dose of ARBs were switched to the fixed-dose combination of losartan (50 mg)/HCTZ (12.5 mg) (mean age 66.9 ± 9.5 years, 51% male, 19% with diabetes mellitus, and 57% with dyslipidemia). After 3 months, losartan/HCTZ treatment significantly reduced mean home systolic BP/diastolic BP from a baseline level of 153 ± 11/85 ± 9 mm Hg to 136 ± 12/77 ± 10 mm Hg (P < .001) and mean clinic BP from 158 ± 9/87 ± 9 to 136 ± 12/77 ± 10 (P < .001), which were maintained through the study period of 12 months (132 ± 11/75 ± 9 and 136 ± 12/77 ± 10; home and clinic BP at 12 months, respectively, P < .001). Furthermore, younger patients (<65 years) receiving ARB monotherapy at the start of the study showed a significantly greater reduction in home BP, but not in clinic BP, compared with elderly patients (≥65 years). In conclusion, losartan/HCTZ combination therapy exerted a 1-year long-term efficacy on home BP as well as clinic BP. In patients uncontrolled with ARB monotherapy, the antihypertensive efficacy on home BP is more pronounced in younger patients compared with that in elderly patients.

Combination of Angiotensin II Receptor Antagonist with Calcium Channel Blocker or Diuretic as Antihypertensive Therapy for Patients with Chronic Kidney Disease

We compared treatment with an angiotensin II receptor antagonist (ARB) and a calcium channel blocker (CCB) combination and a fixed-dose ARB and thiazide diuretic in 18 chronic kidney disease (CKD) patients. A randomized crossover study was performed using a fixed-dose combination of losartan-hydrochlorothiazide or losartan combined with controlled-release nifedipine. Both systolic blood pressure (SBP) and diastolic blood pressures (DBPs) were lower during the nifedipine period than during the diuretic period. No significant difference was observed in urinary albumin excretion, but the estimated glomerular filtration rate was higher in the nifedipine than in the diuretic period. Serum uric acid and low-density lipoprotein cholesterol were higher in the diuretic than in the nifedipine period. A significantly low cardio-ankle vascular index, an index of arterial wall stiffness, was observed in the nifedipine period. A combination of ARB and a controlled-release nifedipine at 20–40 mg used showed a superior antihypertensive effect in CKD patients compared to a fixed-dose combination of losartan 50 mg-hydrochlorothiazide 12.5 mg in terms of blood control. The former combination is considered advantageous for maintaining renal function and artery wall elasticity without influencing uric acid or lipid metabolism.