Combination Therapy with Renin-Angiotensin System Inhibitors and the Calcium Channel Blocker Azelnidipine Decreases Plasma Inflammatory Markers and Urinary Oxidative Stress Markers in Patients with Diabetic Nephropathy

Ogawa, Susumu; Mori, Takefumi; Nako, Kazuhiro; Ito, Sadayoshi

doi:10.1291/hypres.31.1147

Cited by 46 publications

(49 citation statements)

References 42 publications

(48 reference statements)

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“…3 Similar findings have been observed for other CCBs, including azelnidipine 8 and cilnidipine. 9 Several investigators have attempted to explore the mechanism of the renal microvascular action of CCBs, and now have clarified the role of Ca channel subtypes as distinct target sites for CCBs.…”

supporting

confidence: 75%

L-/T-type Ca channel blockers for kidney protection: ready for sophisticated use of Ca channel blockers

Hayashi

2011

Hypertens Res

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supporting

confidence: 75%

L-/T-type Ca channel blockers for kidney protection: ready for sophisticated use of Ca channel blockers

Hayashi

2011

Hypertens Res

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“…[17][18][19][20] AZL is also reported to have the following effects: antioxidative effect, antiatherosclerotic effect, maintaining cerebral blood flow, prevention of proteinuria and PR reduction which is not observed with amlodipine. [21][22][23][24][25] Furthermore, combined use of ARB and AZL is reported to prevent microalbuminuria in diabetic nephropathy patients. 26 A nonclinical study demonstrated that OLM plus CCB combination showed the various preventive effects on vascular injury depending on which CCB was used; AZL was the most effective CCB tested.…”

Section: Safetymentioning

confidence: 99%

A randomized, double-blind, four-arm parallel-group study of the efficacy and safety of azelnidipine and olmesartan medoxomil combination therapy compared with each monotherapy in Japanese patients with essential hypertension: the REZALT study

et al. 2009

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A 12-week randomized, double-blind, four-arm parallel-group, comparative study was conducted in patients with essential hypertension to evaluate the antihypertensive effect and safety of combination therapy with olmesartan medoxomil (OLM, an angiotensin-receptor blocker) 20 mg plus azelnidipine (AZL, a long-acting dihydropyridine calcium channel blocker (20) and AZL (16) monotherapy groups (À12.1/À6.9 and À12.0/À6.9 mm Hg). The proportion of patients achieving the SeBP goal (o130/85 mm Hg for normal BP or o140/90 mm Hg for high-normal BP) was significantly higher in the O/A (20/16) combination group than in the monotherapy groups. The incidence of adverse events was similar in the O/A combination groups and the monotherapy groups. These results showed that combination therapy with O/A was well tolerated and exerted a stronger antihypertensive effect compared with monotherapy with OLM or AZL in patients with essential hypertension.

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“…30,31 With regard to the changes in HSCRP, the anti-inflammatory effects of CCB seem variable; 32 however, it has been reported that azelnidipine, but not nifedipine, reduced plasma inflammatory markers in patients with diabetic nephropathy. 33 Therefore, azelnidipine seems more effective in alleviating oxidative stress and inflammation than other dihydropyridine CCBs.…”

Section: Combined Antihypertensive Therapy With Olmesartan T Ishimitsmentioning

confidence: 99%

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

et al. 2009

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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.

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Combination Therapy with Renin-Angiotensin System Inhibitors and the Calcium Channel Blocker Azelnidipine Decreases Plasma Inflammatory Markers and Urinary Oxidative Stress Markers in Patients with Diabetic Nephropathy

Cited by 46 publications

References 42 publications

L-/T-type Ca channel blockers for kidney protection: ready for sophisticated use of Ca channel blockers

L-/T-type Ca channel blockers for kidney protection: ready for sophisticated use of Ca channel blockers

A randomized, double-blind, four-arm parallel-group study of the efficacy and safety of azelnidipine and olmesartan medoxomil combination therapy compared with each monotherapy in Japanese patients with essential hypertension: the REZALT study

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

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