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

Anadolu Kardiyol Derg. 2014 Dec;14(8):685-91. doi: 10.5152/akd.2014.5049. Epub 2014 Oct 23.


Objective: 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.

Methods: 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).

Results: 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.

Conclusion: 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.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Amlodipine / administration & dosage
  • Amlodipine / therapeutic use*
  • Antihypertensive Agents / administration & dosage
  • Antihypertensive Agents / therapeutic use*
  • Brachial Artery / physiopathology*
  • Drug Therapy, Combination
  • Endothelium, Vascular / physiopathology*
  • Female
  • Humans
  • Hydrochlorothiazide / administration & dosage
  • Hydrochlorothiazide / therapeutic use
  • Hypertension / drug therapy*
  • Losartan / administration & dosage
  • Losartan / therapeutic use
  • Male
  • Pulsatile Flow
  • Treatment Outcome


  • Antihypertensive Agents
  • Hydrochlorothiazide
  • Amlodipine
  • Losartan