Angiotensin-II receptor antagonist combined with calcium channel blocker or diuretic for essential hypertension

Hypertens Res. 2009 Nov;32(11):962-8. doi: 10.1038/hr.2009.133. Epub 2009 Aug 21.


To achieve the target blood pressure recommended by the latest guidelines, multiple antihypertensive drugs are needed in most patients. In this study, the efficacy of treatment using an angiotensin II receptor antagonist (ARB) combined with a calcium channel blocker (CCB) or a diuretic was compared from multiple perspectives in patients with hypertension. Twenty-nine patients with essential hypertension, who had failed to achieve their target blood pressure (<130/85 mm Hg for patients <65 years old and <140/90 mm Hg for those >/=65 years) when treated with the ARB olmesartan at 20 mg day(-1), were additionally given 8-16 mg day(-1) of the CCB azelnidipine or 1-2 mg day(-1) of trichlormethiazide (a thiazide diuretic) in a randomized crossover manner for 4 months each. At the end of each combination therapy period, blood and urine samples were collected and arterial stiffness was evaluated by measuring the cardio-ankle pulse wave velocity. Compared with monotherapy, the blood pressure was reduced similarly by adding azelnidipine (-12/-10 mm Hg) or trichlormethiazide (-14/-9 mm Hg). The heart rate was decreased with the CCB by 4 b.p.m. (P<0.05), whereas it was unchanged with the thiazide. Serum K, lipids and blood glucose were not significantly changed with either combination, whereas serum uric acid was increased with the thiazide (P<0.01) but was unchanged with azelnidipine. Plasma levels of renin, angiotensin II and aldosterone were also increased with the thiazide period, whereas high-sensitivity C-reactive protein and oxidized low-density lipoprotein were decreased with azelnidipine. In addition, the cardio-ankle vascular index, a parameter of arterial stiffness, was decreased with the azelnidipine period but was unchanged with the thiazide period (P<0.01). It is suggested that the combination of olmesartan and azelnidipine has advantages over the combination of olmesartan and a thiazide with respect to avoiding hyperuricemia, sympathetic activation, renin-angiotensin-aldosterone system stimulation, inflammation, oxidative stress, and increased arterial stiffness in patients with moderate hypertension. These properties may provide cardiovascular protection in addition to the hypotensive effect.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Albuminuria / drug therapy
  • Albuminuria / urine
  • Angiotensin II Type 1 Receptor Blockers / therapeutic use*
  • Ankle Brachial Index
  • Azetidinecarboxylic Acid / analogs & derivatives
  • Azetidinecarboxylic Acid / therapeutic use
  • Blood Pressure / drug effects
  • C-Reactive Protein / metabolism
  • Calcium Channel Blockers / therapeutic use*
  • Cross-Over Studies
  • Dihydropyridines / therapeutic use
  • Diuretics / therapeutic use*
  • Drug Therapy, Combination
  • Female
  • Glomerular Filtration Rate
  • Humans
  • Hypertension / drug therapy*
  • Hypertension / physiopathology
  • Imidazoles / therapeutic use
  • Lipoproteins, LDL / blood
  • Male
  • Middle Aged
  • Sodium Chloride Symporter Inhibitors / therapeutic use
  • Tetrazoles / therapeutic use
  • Trichlormethiazide / therapeutic use


  • Angiotensin II Type 1 Receptor Blockers
  • Calcium Channel Blockers
  • Dihydropyridines
  • Diuretics
  • Imidazoles
  • Lipoproteins, LDL
  • Sodium Chloride Symporter Inhibitors
  • Tetrazoles
  • Azetidinecarboxylic Acid
  • olmesartan
  • C-Reactive Protein
  • azelnidipine
  • Trichlormethiazide