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1.
Comparison of efficacy and safety between benidipine and hydrochlorothiazide in fosinopril-treated hypertensive patients with chronic kidney disease: protocol for a randomised controlled trial.
Xue, C, Zhou, C, Yang, B, Lv, J, Dai, B, Yu, S, Wang, Y, Zhao, G, Mei, C
BMJ open. 2017;(2):e013672
Abstract
INTRODUCTION Co-administration of a diuretic or calcium channel blocker with an ACE inhibitor are both preferred combinations in patients with hypertensive chronic kidney disease (CKD). According to the available evidence, it is still unknown which combination plays a more active role in renal protection. We hypothesised that a combination of fosinopril and benidipine may delay the progression of CKD more effectively than a combination of fosinopril and hydrochlorothiazide (HCTZ). METHODS AND ANALYSIS This study will be a multicentred, prospective, double-blind, randomised parallel controlled trial for hypertensive CKD patients in China. Patients will be randomised to one of two treatment groups: a combination of benidipine 4-8 mg/day and fosinopril 20 mg/day; or a combination of HCTZ 12.5-25 mg/day and fosinopril 20 mg/day. Patients will be followed up for 24 months after a month's fosinopril run-in. There will be dose-titration after 1 and 2 months. The primary endpoint is changes in estimated glomerular filtration rate (eGFR) from baseline to month 24. Secondary endpoints include changes in home blood pressure (BP), ambulatory BP, proteinuria, urinary albumin/creatinine ratio, and composite renal events in 24 months. Inclusion criteria are: age 18-80 years, non-dialysis CKD patients with eGFR >30 mL/min/1.73 m2, home BP >130 mm Hg systolic or BP >80 mm Hg diastolic at the screening and randomisation, and 24 hour proteinuria <3.5 g. Principal exclusions are hypertensive crisis, transplantation, cancer, severe diabetes complications, hyperkalaemia and severe allergy. The required sample size was 511 patients for detecting a difference in the change of eGFR (one sided α=0.025, power 1-β=0.90). ETHICS AND DISSEMINATION BEAHIT (Benidipine and Hydrochlorothiazide in Fosinopril Treated Chronic Kidney Disease Patients with Hypertension) was approved by Changzheng Hospital Ethics Committee (CZ-20160504-16). The outcomes will be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER NCT02646397.
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Efficacy and safety of lercanidipine/enalapril fixed combination in Lebanon: a prospective observational study.
Arnaout, S, ,
Current medical research and opinion. 2015;(1):187-90
Abstract
OBJECTIVE The DUAL study evaluated the effectiveness and safety of the fixed-dose combination of lercanidipine and enalapril in a real-practice scenario; the effects of this combination on a number of markers of cardiovascular risk have been also investigated. RESEARCH DESIGN AND METHODS This was a 2 month, phase IV, open-label, single-group, prospective observational study. Adult patients with untreated or uncontrolled hypertension (blood pressure [BP] >140/90 mmHg) were eligible for this study. All patients received lercanidipine/enalapril, in a once-daily fixed combination (10 mg/10 mg). MAIN OUTCOME MEASURES The patients were evaluated at baseline, at 1 month and at 2 months. The following parameters were evaluated at all time points: systolic BP (SBP) and diastolic BP (DBP); heart rate (HR). A number of laboratory parameters were measured at baseline and at 2 months. Safety considerations were performed. RESULTS In total, 188 patients were enrolled (104 males; mean age 58 ± 12 years). At baseline, mean SBP was 159 ± 10 mmHg and mean DBP was 94 ± 7 mmHg. Treatment with lercanidipine/enalapril in fixed combination was associated with a reduction in both SBP and DBP already at 1 month; this reduction was sustained until month 2 (SBP: 131 ± 7 mmHg; DBP: 79 ± 5 mmHg; p < 0.05 vs baseline). At baseline HR was 78 ± 10 bpm; a significant reduction in this parameter was observed at month 2 (75 ± 7 bpm; p < 0.05 vs baseline). A significant decrease in total cholesterol, low-density lipoprotein cholesterol, triglycerides, and fasting glucose, and a significant increase in K(+), and Ca(2+) was observed at month 2 compared with baseline values. In total, two patients (1%) experienced dry cough. No other adverse effects were reported. CONCLUSIONS Even with all the limitations of any observational study, these data show that a 2 month treatment with a fixed dose of lercanidipine/enalapril is associated with significant reductions in SBP and DBP, HR, and improvement in a number of laboratory parameters.
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3.
Antiplatelet effect of clopidogrel can be reduced by calcium-channel blockers.
Seo, KD, Kim, YD, Yoon, YW, Kim, JY, Lee, KY
Yonsei medical journal. 2014;(3):683-8
Abstract
PURPOSE Clopidogrel is metabolized by the hepatic cytochrome P450 (CYP) system into its active thiol metabolite. CYP3A4 is involved in the metabolism of both clopidogrel and dihydropyridine calcium channel blockers (CCBs). A few reports have suggested an inhibitory interaction between CCBs and clopidogrel. Accordingly, the aim of this study was to determine the effect of CCBs on the antiplatelet activity of clopidogrel by serial P2Y12 reaction unit (PRU) measurements. MATERIALS AND METHODS We assessed changes in antiplatelet activity in patients receiving both clopidogrel and CCBs for at least 2 months prior to enrollment in the study. The antiplatelet activity of clopidogrel was measured by VerifyNow P2Y12 assay in the same patient while medicated with CCBs and at 8 weeks after discontinuation of CCBs. After discontinuation of the CCBs, angiotensin receptor blockers were newly administered to the patients or dosed up for control of blood pressure. RESULTS Thirty patients finished this study. PRU significantly decreased after discontinuation of CCBs (238.1±74.1 vs. 215.0±69.3; p=0.001). Of the 11 patients with high post-treatment platelet reactivity to clopidogrel (PRU≥275), PRU decreased in nine patients, decreasing below the cut-off value in seven of these nine patients after 8 weeks. Decrease in PRU was not related to CYP2C19 genotype. CONCLUSION CCBs inhibit the antiplatelet activity of clopidogrel.
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4.
Changes in left ventricular relaxation after azelnidipine treatment in hypertensive patients with diabetes: subanalysis of a prospective single-arm multicentre study.
Iwakura, K, Ito, H, Ishii, K, Date, M, Nakamura, F, Nagano, T, Takiuchi, S, ,
BMJ open. 2014;(9):e006136
Abstract
OBJECTIVES We previously demonstrated that a calcium channel blocker, azelnidipine, improves left ventricular relaxation in patients with hypertension and diastolic dysfunction in a multicentre, Clinical impact of Azelnidipine on Left VentricuLar diastolic function and OutComes in patients with hypertension (CALVLOC) trial. The objectives of the present subanalysis were to investigate the differences in diastolic function in hypertensive patients with and without diabetes, and the efficacy of azelnidipine on diastolic function among them. DESIGN Subanalysis of a prospective single-arm multicentre study. PARTICIPANTS 228 hypertensive patients with normal ejection fraction and impaired left ventricular relaxation (septal e' velocity<8 cm/s on echocardiography) enrolled for CALVLOC trial. They were divided into two groups based on presence or absence of diabetes. INTERVENTIONS Administration of 16 mg of azelnidipine for 8 months (range 6-10 months). MAIN OUTCOME MEASURES Septal e' velocity before and at the end of the study. RESULTS Whereas patients with diabetes (n=53, 23.2%) had lower systolic blood pressure (BP) than patients without diabetes (155±17 vs 161±16 mm Hg, p=0.03), they had lower e' velocity (5.7±1.5 vs 6.1±1.4 cm/s, p=0.04) at baseline. Azelnidipine decreased BP and heart rate, and increased e' velocity similarly in patients with diabetes (5.7±1.5 to 6.3±1.5 cm/s, p=0.0003) and without diabetes (6.1±1.4 to 6.9±1.4 cm/s, p<0.0001). Increase in e' velocity was not influenced by presence of diabetes, and patients with diabetes still had lower e' velocity after treatment (p=0.006). There was a significant correlation between increase in e' velocity and decrease in systolic BP (R=0.25, p=0.0001), which was not influenced by diabetes. CONCLUSIONS Comorbid diabetes could impair left ventricular relaxation independently in patients with hypertension, which might not be improved solely by BP lowering.
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5.
Effects of azelnidipine on uric acid metabolism in patients with essential hypertension.
Miyazaki, S, Hamada, T, Hirata, S, Ohtahara, A, Mizuta, E, Yamamoto, Y, Kuwabara, M, Nosaka, Y, Igawa, O, Ogino, K, et al
Clinical and experimental hypertension (New York, N.Y. : 1993). 2014;(7):447-53
Abstract
PURPOSE To examine effects of a long-acting calcium channel blocker (CCB) azelnidipine on uric acid metabolism in hypertensive patients. METHODS Azelnidipine was administered to 72 patients at a daily dose of 8 mg or 16 mg. In 22 cases out of the 72 patients, a different CCB was switched to azelnidipine. Blood pressure was measured and biochemical parameters of blood and urine were evaluated before and 2-3 months after the administration. RESULTS Azelnidipine significantly decreased both systolic and diastolic blood pressure and the heart rate. It decreased both serum urate levels and the urinary uric acid to creatinine ratio (Uur/Ucr), but did not affect the uric acid clearance to creatinine clearance ratio (Cur/Ccr). Azelnidipine decreased both Uur/Ucr and Cur/Ccr in patients with Uur/Ucr ≥ 0.5 or ≥ 0.34, although it did not change these clearance parameters in patients with Uur/Ucr <0.5 or <0.34. Azelnidipine decreased the serum urate levels and Uur/Ucr in hyperuricemic patients with uric acid levels ≥ 7.0 mg/dL in males and ≥ 6.0 mg/dL in females. It did not change these parameters in normouricemic patients with serum urate levels <7.0 mg/dL in males and <6.0 mg/dL in females. Azelnidipine decreased Uur/Ucr and Cur/Ccr in hyperuricemic patients with normal or over excretion of uric acid, although it did not change these clearance parameters in hyperuricemic patients with uric acid hypoexcretion. CONCLUSIONS Azelnidipine decreased the serum urate acid levels and Uur/Ucr, and this response was most prominent in hyperuricemic patients or patients with normal and over excretion of uric acid.
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Blood pressure and metabolic effect of a combination of lercanidipine with different antihypertensive drugs in clinical practice.
Cicero, AF, Gerocarni, B, Rosticci, M, Borghi, C
Clinical and experimental hypertension (New York, N.Y. : 1993). 2012;(2):113-7
Abstract
The aim of this study is to assess the blood pressure (BP) and metabolic effects of lercanidipine when combined with other classes of first-line antihypertensive drugs in day-to-day clinical practice. For this study, we consecutively enrolled 162 patients with uncomplicated primary hypertension, who are partial responders to the treatment with lercanidipine over a period of 24 months. Patients were then allocated to the combination of lercanidipine (10-20 mg/day) with β-blockers, diuretics, angiotensin-converting enzyme inhibitors, and angiotensin-II receptor blockers according to compelling indications (if any) and/or suggestions of European Society of Hypertension-European Society of Cardiology (ESH-ESC) guidelines. All the enrolled patients completed the study and no adverse drug reaction was registered during the research period. The association of a second drug with lercanidipine determined an additional BP decrease of either systolic BP or diastolic BP independently from the type of drug added (P always <.05). The additional effect of lercanidipine appears widely distributed with no significant differences in the size of BP decrease. From the metabolic point of view, the addition of a second drug did not determine a significant variation in the serum levels of total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol (P always >.05). Conversely, a significant decrease in fasting plasma glucose and serum levels of triglycerides has been observed in patients where lercanidipine has been combined with an angiotensin-converting enzyme inhibitor or an angiotensin-II receptor blocker. In conclusion, in our study we observed that lercanidipine-based protocols are well tolerated and efficacious in reducing BP. Moreover, the association of lercanidipine with renin-angiotensin system blockers is also associated with significant improvements in triglycerides and fasting plasma glucose.
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7.
[Azelnidipine and amlodipine anti-coronary atherosclerosis trial in hypertensive patients undergoing coronary intervention by serial volumetric intravascular ultrasound analysis in Juntendo Medical University].
Miyauchi, K, Daida, H
Nihon Naika Gakkai zasshi. The Journal of the Japanese Society of Internal Medicine. 2012;(10):3002-11
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8.
Azelnidipine, a long-acting calcium channel blocker, could control hypertension without decreasing cerebral blood flow in post-ischemic stroke patients. A 123I-IMP SPECT follow-up study.
Watanabe, M, Hirano, T, Okamoto, S, Shiraishi, S, Tomiguchi, S, Uchino, M
Hypertension research : official journal of the Japanese Society of Hypertension. 2010;(1):43-8
Abstract
Azelnidipine, a long-acting calcium channel blocker, is highly lipid soluble and selective for the vascular wall, and is expected to have an increasing effect on cerebral blood flow (CBF). The aim of this study is to investigate its safety and efficacy in stroke patients in the chronic stage as far as CBF is concerned using N-isopropyl-p-(123)I-iodo amphetamine ((123)I-IMP) single-photon emission computed tomography (SPECT). The patients were orally administered 8 or 16 mg of azelnidipine. Regional CBF was evaluated by (123)I-IMP SPECT using three-dimensional stereotactic region-of-interest (ROI) template (3D-SRT), a technique using anatomical standardization and ROI template consisting of 636 ROIs for the whole brain. Mean hemispheric CBF was defined as the mean value of the corpus callosum, and the precentral, central, parietal, angular and temporal gyri. Mean hemispheric and regional CBF after 1, 3 and 6 months were analyzed using a one-way repeated-measures analysis of variance. Ten post-ischemic stroke patients with hypertension were enrolled between October 2005 and October 2007, and all of them were well controlled with normal blood pressure (before: 172.3+/-16.6/88.4+/-14.0 mm Hg; 6 months: 128.7+/-15.9/70.9+/-10.1 mm Hg). No vascular events were observed during the study period. The mean hemispheric CBF was maintained during the study period (before: 46.0+/-9.7 ml per 100 g per min; 6 months: 49.3+/-11.1 ml per 100 g per min). The regional CBF was also maintained. In the chronic stage of ischemic stroke, azelnidipine could safely decrease systemic blood pressure without decreasing CBF.
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Stress-induced blood pressure elevation in subjects with mild cognitive impairment: effects of the dual-type calcium channel blocker, cilnidipine.
Kawashima, Y, Akishita, M, Hasegawa, H, Kozaki, K, Toba, K
Geriatrics & gerontology international. 2008;(4):278-83
Abstract
AIM: We investigated whether mental stress-induced blood pressure elevation was related to cognitive function in the elderly, and further examined the effects of the dual-type calcium channel blocker, cilnidipine, on stress induced hypertension in subjects with mild cognitive impairment. METHODS In study I, 39 consecutive outpatients (mean age +/- standard deviation, 77 +/- 8 years), who were referred to our memory clinic and were not taking any medications, were studied. They were divided into three groups according to cognitive function on the Hasegawa Dementia Scale-Revised (HDSR): group 1 (n = 8), 28 points or more; group 2 (n = 18), 21-27 points; and group 3 (n = 13), 20 points or less. In study II, 14 outpatients with hypertension and mild cognitive impairment (aged 79 +/- 8 years; HDSR score, 24 +/- 4) were assigned to receive cilnidipine (10-20 mg/day). The control group (n = 10) matched for age, HDSR and blood pressure was followed without cilnidipine. RESULTS In study I, although age and basal blood pressure were similar among the three groups, the blood pressure response to a mental arithmetic test was twice as large in group 2 (26 +/- 12 mmHg in systolic pressure and 11 +/- 8 mmHg in diastolic pressure) as those in groups 1 and 3. In study II, after 4 weeks, cilnidipine treatment significantly decreased the blood pressure responses to the mental arithmetic test compared to the baseline as well as to those of the control group. CONCLUSIONS Stress-induced blood pressure elevations are exaggerated in subjects with mild cognitive impairment. Cilnidipine may have inhibitory effects on stress-induced hypertension.
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10.
Effects of azelnidipine on the autonomic functions and its influence on arterial stiffness and endothelial functions.
Yamada, J, Tomiyama, H, Matsumoto, C, Yoshida, M, Shiina, K, Yamashina, A
Journal of cardiology. 2008;(2):114-20
Abstract
BACKGROUND The present study was conducted to clarify whether azelnidipine might have beneficial effects on autonomic functions, and whether such beneficial effects might affect the vascular functions (i.e., arterial stiffness and endothelial function). METHODS AND RESULTS This study with a cross-over design was conducted in 21 hypertensive patients (65 +/- 9 years old) being treated with calcium channel blockers (CCBs) other than azelnidipine or benidipine (i.e., during the study period, the CCB was switched to either azelnidipine 16 mg/day or benidipine 4 mg/day, administered alternately for 8 weeks each). Blood examinations were conducted and the heart rate variability, baro-receptor sensitivity (BRS), brachial-ankle pulse wave velocity (baPWV) and flow-mediated vasodilatation (FMD) in the brachial artery were measured after treatment with each of the two drugs. While the blood pressure levels decreased to a similar degree after both treatments, the BRS (8.8 +/- 5.5 ms/mmHg vs. 6.4 +/- 2.9 ms/mmHg, p < 0.01) and high-frequency power component (HF: 139 +/- 152 ms2/Hz vs. 88 +/- 97 ms2/Hz) were higher after treatment with azelnidipine than after treatment with benidipine (p < 0.05). However, the baPWV, FMD and plasma levels of malonyldialdehyde low-density lipoprotein cholesterol and nitric oxides were similar after treatment with both drugs. CONCLUSION Azelnidipine has greater beneficial effects on the autonomic functions than benidipine although the degree of reduction of blood pressure induced by the two drugs was similar. However, this greater beneficial effect of azelnidipine on the autonomic functions did not produce any distinguishable differences in effects of azelnidipine and benidipine on the arterial stiffness and endothelial functions.