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

Abstract

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 (o130/85 mm Hg for patients o65 years old and o140/90 mm Hg for those X65 years) when treated with the ARB olmesartan at 20 mg day À1 , were additionally given 8-16 mg day À1 of the CCB azelnidipine or 1-2 mg day À1 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 (À12/À10 mm Hg) or trichlormethiazide (À14/À9 mm Hg). The heart rate was decreased with the CCB by 4 b.p.m. (Po0.05), 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 (Po0.01) 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 (Po0.01). 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.

The Effects of Antihypertensive Agents in Metabolic Syndrome – Benefits Beyond Blood Pressure Control

“…Similar data were shown in a 4-month crossover study comparing olmesartan medoxomil plus azelnidipine or trichlormethiazide [111] [112]. When combined with atorvastatin, amlodipine therapy reduces plasma hsCRP significantly [104].…”

Association of renal function with the ambulatory arterial stiffness index and pulse pressure in hypertensive patients

“…Some studies have shown that the CKD-EPI formula is more accurate than the MDRD equation and it can replace it for routine clinical use. 28,30,31 Our results showed that the value of eGFR measured by the MDRD formula was lower than that estimated with the CKD-EPI formula. In a study by Ratto et al 21 the risk of a mild reduction in eGFR increased almost twofold for each s.d.…”

“…Numerous studies have shown a decrease in arterial stiffness with various pharmacological classes of antihypertensive agents. 24,[31][32][33] Moreover protecting the kidneys by reducing BP, antihypertensive drugs can also have direct effects on intrarenal mechanisms of damage, such as increased glomerular pressure and proteinuria. 26,34,35 Additionally, the use of hypertensive agents might affect the degree of nocturnal BP fall, which is considered as an important factor for Abbreviations: ACR, urinary albumin-to-urinary creatinine ratio; BMI, body mass index; DBP, diastolic blood pressure; eGFR, estimated glomerular filtration rate; HDL, high-density lipoprotein; MBP, mean blood pressure; MDRD, modification of diet in renal disease; PP, pulse pressure; RAAS, renin-angiotensin-aldosterone system; SBP, systolic blood pressure.…”

Cardio-Ankle Vascular Index (CAVI) as a Novel Indicator of Arterial Stiffness: Theory, Evidence and Perspectives

“…Ishimitsu et al 49) reported that the combination of olmesartan and azelnidipine has advantages over the combination of olmesartan and a thiazide with respect to avoiding increased arterial stiffness in patients with moderate hypertension. A tablet combining losartan and hydrochlorothiazide has been found to decrease CAVI 50) .…”