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Drug Design, Development and Therapy (submit here)

This international, peer-reviewed Open Access journal by Dove Medical Press focuses on the design and development of drugs, as well as the clinical outcomes, patient safety, and programs targeted at the effective and safe use of medicines. Sign up for email alerts here.

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Azelnidipine plus olmesartan versus amlodipine plus olmesartan on arterial stiffness and cardiac function in hypertensive patients: a randomized trial

Author(s): Takeshi Takami, Yoshihiko Saito

Publication date: 2013-03-22

Journal: Drug Design, Development and Therapy

Publisher: Dove Medical Press

Keywords: arterial stiffness, central blood pressure, left ventricular diastolic function, left ventricular mass index, olmesartan/azelnidipine

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Abstract

Purpose To compare the long-term effects of olmesartan combined with either azelnidipine or amlodipine on central blood pressure (CBP), left ventricular (LV) mass index (LVMI), LV diastolic function (e′ velocity, E/e′ ratio, E/A ratio) and arterial stiffness (brachial-ankle pulse wave velocity [baPWV] and augmentation index normalized for a heart rate of 75 bpm [AIx]). Patients and methods Patients with systolic BP ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg received olmesartan monotherapy (20 mg/day) for 12 weeks. They were then randomly assigned to fixed-dose add-on therapy with azelnidipine (16 mg/day; n = 26) or amlodipine (5 mg/day; n = 26) for a further 2 years. CBP, LVMI, e′ velocity, E/e′ ratio, E/A ratio, baPWV, and AIx were measured at baseline, 6 months, and 2 years. Results Baseline characteristics of both groups were similar. The decrease in brachial BP over 2 years was similar in both groups. CBP, LVMI, E/e′ ratio, baPWV, and AIx decreased significantly, and the E/A ratio and e′ velocity increased significantly in both groups. The decreases in CBP (P < 0.001), AIx (P < 0.001), baPWV (P < 0.001), LVMI (P < 0.001), and E/e′ (P = 0.002) as well as the increase in E/A ratio (P = 0.03) over 2 years were significantly greater in the olmesartan/azelnidipine group than in the olmesartan/amlodipine group. Multivariate linear regression analyses showed that the changes in baPWV (β = 0.41, P < 0.001) and CBP (β = 0.47, P = 0.01) were independently associated with the change in LVMI, the change in baPWV (β = 0.25, P < 0.001) was independently associated with the change in E/e′ ratio, and the changes in baPWV (β = 0.21, P = 0.001) and AIx (β = 0.25, P = 0.03) were independently associated with the change in E/A ratio. Conclusion Treatment with olmesartan/azelnidipine for 2 years resulted in greater improvements in CBP, LVMI, and LV diastolic function, and arterial stiffness compared with olmesartan/amlodipine. Improvements in LV diastolic function were associated with improvements in arterial stiffness.

Most cited references 28

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The Japanese Society of Hypertension Guidelines for the Management of Hypertension (JSH 2009).

Genjiro Kimura, Jitsuo Higaki, Toshio Ogihara … (2008)

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Noninvasive estimation of left ventricular filling pressure by E/e' is a powerful predictor of survival after acute myocardial infarction.

G Hillis, William K. Oh, J Möller … (2004)

The aim of this study was to assess the prognostic value of a noninvasive measure of left ventricular diastolic pressure (LVDP) early after acute myocardial infarction (MI). The early diastolic velocity of the mitral valve annulus (e') reflects the rate of myocardial relaxation. When combined with measurement of the early transmitral flow velocity (E), the resultant ratio (E/e') correlates well with mean LVDP. In particular, an E/e' ratio >15 is an excellent predictor of an elevated mean LVDP. We hypothesized that an E/e' ratio >15 would predict poorer survival after acute MI. Echocardiograms were obtained in 250 unselected patients 1.6 days after admission for MI. Patients were followed for a median of 13 months. The end point was all-cause mortality. Seventy-three patients (29%) had an E/e' >15. This was associated with excess mortality (log-rank statistic 21.3, p 15 improved the prognostic utility of a model containing clinical variables and conventional echocardiographic indexes of left ventricular systolic and diastolic function (p = 0.001). E/e' is a powerful predictor of survival after acute MI. An E/e' ratio >15 is superior, in this respect, to other clinical or echocardiographic features. Furthermore, it provides prognostic information incremental to these parameters.

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Relation of arterial stiffness to diastolic dysfunction in hypertensive heart disease.

P M Mottram, B Haluska, R Leano … (2005)

To examine the relation of arterial compliance to diastolic dysfunction in hypertensive patients with suspected diastolic heart failure (HF). 70 medically treated hypertensive patients with exertional dyspnoea (40 women, mean (SD) age 58 (8) years) and 15 normotensive controls. Mitral annular early diastolic velocity with tissue Doppler imaging and flow propagation velocity were used as linear measures of diastolic function. Arterial compliance was determined by the pulse pressure method. According to conventional Doppler echocardiography of transmitral and pulmonary venous flow, diastolic function was classified as normal in 33 patients and abnormal in 37 patients. Of those with diastolic dysfunction, 28 had mild (impaired relaxation) and nine had advanced (pseudonormal filling) dysfunction. Arterial compliance was highest in controls (mean (SD) 1.32 (0.58) ml/mm Hg) and became progressively lower in patients with hypertension and normal function (1.04 (0.37) ml/mm Hg), impaired relaxation (0.89 (0.42) ml/mm Hg), and pseudonormal filling (0.80 (0.45) ml/mm Hg, p = 0.011). In patients with diastolic dysfunction, arterial compliance was inversely related to age (p = 0.02), blood pressure (p < 0.001), and estimated filling pressures (p < 0.01) and directly related to diastolic function (p < 0.01). After adjustment for age, sex, body size, blood pressure, and ventricular hypertrophy, arterial compliance was independently predictive of diastolic dysfunction. In hypertensive patients with exertional dyspnoea, progressively abnormal diastolic function is associated with reduced arterial compliance. Arterial compliance is an independent predictor of diastolic dysfunction in patients with hypertensive heart disease and should be considered a potential target for intervention in diastolic HF.