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.