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Treatment effect of lacidipine and amlodipine on clinic and ambulatory blood pressure and arteria stiffness in a randomised double-blind trial.
Wang, Y, Li, Y, Huo, Y, Wang, JG
Blood pressure. 2021;(2):108-117
Abstract
PURPOSE In a randomised, double-blind trial, we investigated effects of lacidipine on clinic and ambulatory blood pressure (BP) and arterial stiffness in patients with mild-to-moderate hypertension, as compared with amlodipine. MATERIALS AND METHODS Previously untreated and treated patients (n = 269, 50-80 years of age) with clinic hypertension (a clinic systolic/diastolic BP 140-180/<110 mmHg and <160/100 mmHg, respectively) were randomly assigned to double-dummy treatment with lacidipine (4-6 mg/day) or amlodipine (5-7.5 mg/day) for 20 weeks. The primary efficacy variable was the change in 24-h ambulatory systolic BP at 20 weeks of treatment. Arterial stiffness was measured as brachial-ankle pulse wave velocity (PWV). RESULTS After 20 weeks of treatment, 24-h systolic BP decreased from 141.3 ± 14.0 and 138.3 ± 12.8 mmHg at baseline, respectively, in the lacidipine (n = 134) and amlodipine groups (n = 135), by a least square mean (±SE) change of 15.2 ± 1.3 and 15.5 ± 1.3 mmHg, respectively, with a between-group difference (95% confidence interval [CI]) of 0.3 mmHg (-3.4 to 4.1, p = 0.86). Similar results were observed for other ambulatory BP components and clinic BP. Clinic and ambulatory pulse rate did not significantly change in either group (p ≥ 0.21). PWV decreased significantly (p < 0.001) from baseline in both groups, with a non-significant between-group difference of 0.24 m/s (p = 0.45). The incidence rate of adverse events was 30.3% (n = 40) and 27.5% (n = 36) in the lacidipine and amlodipine groups, respectively (p = 0.61). No serious adverse event occurred in the trial. CONCLUSIONS Lacidipine effectively lowers clinic and ambulatory BP in patients with mild-to-moderate hypertension and significantly improves arterial stiffness, similarly as amlodipine.
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The effect of an L/N-type calcium channel blocker on intradialytic blood pressure in intradialytic hypertensive patients.
Ito, T, Fujimoto, N, Ishikawa, E, Dohi, K, Fujimoto, M, Murata, T, Kiyohara, M, Takeuchi, H, Koyabu, S, Nishimura, H, et al
Clinical and experimental hypertension (New York, N.Y. : 1993). 2019;(1):92-99
Abstract
BACKGROUND Intradialytic hypertension (HTN), which is one of the poor prognostic markers in patients undergoing hemodialysis, may be associated with sympathetic overactivity. The L/N-type calcium channel blocker, cilnidipine, has been reported to suppress sympathetic nerves activity in vivo. Therefore, we hypothesized that cilnidipine could attenuate intradialytic systolic blood pressure (SBP) elevation. METHODS Fifty-one patients on chronic hemodialysis who had intradialytic-HTN (SBP elevation ≥10 mmHg during hemodialysis) and no fluid overload were prospectively randomized into two groups: control and cilnidipine groups. Cilnidipine group patients took cilnidipine (10 mg/day) for 12 weeks. The primary endpoint was the change in the intradialytic SBP elevation before and after the 12-week intervention. RESULTS Before the intervention, no differences were observed in age, sex or pre-dialytic SBP (148.5 ± 12.9 vs. 148.3 ± 19.3 mmHg) between the two groups. Intradialytic SBP elevation was unchanged in the control group. Cilnidipine significantly lowered the post-dialytic SBP with an attenuation of the intradialytic SBP elevation from 12.0 ± 15.4 mmHg to 4.8 ± 10.1 mmHg. However, the observed difference in the intradialytic SBP elevation by cilnidipine did not reach statistical significance (group×time interaction effect p = 0.25). Cathecolamine levels were unaffected by the intervention in both groups. CONCLUSION Cilnidipine lowers both the pre- and post-dialytic SBP and might attenuate intradialytic SBP elevation. Therefore, cilnidipine may be effective in lowering SBP during HD in patients with intradialytic-HTN.
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Reduction in microalbuminuria by calcium channel blockers in patients with type 2 diabetes mellitus and hypertension-A randomized, open-label, active-controlled, superiority, parallel-group clinical trial.
Hwang, YC, Yoon, KH, Cha, BS, Lee, KW, Jang, HC, Min, KW, Chung, CH, Lee, MK
International journal of clinical practice. 2017;(9)
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Abstract
BACKGROUND It has been suggested that renoprotection with calcium channel blockers (CCBs) may differ. This study aimed to compare the anti-proteinuric effect of different CCBs in patients with type 2 diabetes (T2D). METHODS A multicentre, randomized, open-label, active-controlled study was performed in seven centres in Korea. A total of 74 patients with T2D and microalbuminuria treated with renin-angiotensin system (RAS) blockers were randomized to a cilnidipine 10 mg treatment (n=38) or amlodipine 5 mg treatment (n=36). RESULTS Urine albumin to creatinine ratio (ACR) reduction was similar between the two groups at 12 weeks (-53.0±123.2 mg/g in cilnidipine group and -35.7±83.6 mg/g in amlodipine group, P=.29) or 24 weeks (-57.3±106.9 mg/g in cilnidipine group and -20.0±110.4 mg/g in amlodipine group, P=.24). In a subgroup analysis, cilnidipine treatment showed a larger ACR reduction than amlodipine treatment at 12 weeks (-84.7±106.8 mg/g in cilnidipine group and -9.5±79.2 mg/g in amlodipine group, P=.01) and 24 weeks (-84.0±111.7 mg/g in cilnidipine group and 14.6±119.4 mg/g in amlodipine group, P=.008), particularly in patients with a longer duration of diabetes more than 10 years. CONCLUSIONS Cilnidipine did not show any additional anti-albuminuric effect compared with amlodipine in patients with T2D and microalbuminuria treated with an RAS blocker. However, the anti-albuminuric effect of cilnidipine might differ according to the duration of diabetes.
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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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Calcium channel blockade blunts the renal effects of acute nitric oxide synthase inhibition in healthy humans.
Montanari, A, Lazzeroni, D, Pelà, G, Crocamo, A, Lytvyn, Y, Musiari, L, Cabassi, A, Cherney, DZI
American journal of physiology. Renal physiology. 2017;(5):F870-F878
Abstract
Our aim was to investigate whether blockade of calcium channels (CCs) or angiotensin II type 1 receptors (AT1R) modulates renal responses to nitric oxide synthesis inhibition (NOSI) in humans. Fourteen sodium-replete, healthy volunteers underwent 90-min infusions of 3.0 μg·kg-1·min-1 NG-nitro-l-arginine methyl ester (l-NAME) on 3 occasions, preceded by 3 days of either placebo (PL), 10 mg of manidipine (MANI), or 50 mg of losartan (LOS). At each phase, mean arterial pressure (MAP), glomerular filtration rate (GFR; inulin), renal blood flow (RBF; p-aminohippurate), urinary sodium (UNaV), and 8-isoprostane (U8-iso-PGF2αV; an oxidative stress marker) were measured. With PL + l -NAME, the following changes were observed: +6% MAP (P < 0.005 vs. baseline), -10% GFR, -20% RBF, -49% UNaV (P < 0.001), and +120% U8-iso-PGF2αV (P < 0.01). In contrast, MAP did not increase during LOS + l-NAME or MANI + l-NAME (P > 0.05 vs. baseline), whereas renal changes were the same during LOS + l-NAME vs. PL + l-NAME (ANOVA, P > 0.05). However, during MANI + l-NAME, changes vs. baseline in GFR (-6%), RBF (-12%), and UNaV (-34%) were blunted vs. PL + l-NAME and LOS + l-NAME (P < 0.005), and the rise in U8-iso-PGF2αV was almost abolished (+37%, P > 0.05 vs. baseline; P < 0.01 vs. PL + l-NAME or LOS + l-NAME). We conclude that, since MANI blunted l-NAME-induced renal hemodynamic changes, CCs participate in the renal responses to NOSI in healthy, sodium-replete humans independent of changes in MAP and without the apparent contribution of the AT1R. Because the rise in U8-iso-PGF2αV was essentially prevented during MANI + l-NAME, CC blockade may oppose the renal effects of NOSI in part by counteracting oxidative stress responses to acutely impaired renal NO bioavailability.
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Long-term effects of L- and N-type calcium channel blocker on uric acid levels and left atrial volume in hypertensive patients.
Masaki, M, Mano, T, Eguchi, A, Fujiwara, S, Sugahara, M, Hirotani, S, Tsujino, T, Komamura, K, Koshiba, M, Masuyama, T
Heart and vessels. 2016;(11):1826-1833
Abstract
Left ventricular (LV) diastolic dysfunction is associated with hypertension and hyperuricemia. However, it is not clear whether the L- and N-type calcium channel blocker will improve LV diastolic dysfunction through the reduction of uric acid. The aim of this study was to investigate the effects of anti-hypertensive therapy, the L- and N-type calcium channel blocker, cilnidipine or the L-type calcium channel blocker, amlodipine, on left atrial reverse remodeling and uric acid in hypertensive patients. We studied 62 patients with untreated hypertension, randomly assigned to cilnidipine or amlodipine for 48 weeks. LV diastolic function was assessed with the left atrial volume index (LAVI), mitral early diastolic wave (E), tissue Doppler early diastolic velocity (E') and the ratio (E/E'). Serum uric acid levels were measured before and after treatment. After treatment, systolic and diastolic blood pressures equally dropped in both groups. LAVI, E/E', heart rate and uric acid levels decreased at 48 weeks in the cilnidipine group but not in the amlodipine group. The % change from baseline to 48 weeks in LAVI, E wave, E/E' and uric acid levels were significantly lower in the cilnidipine group than in the amlodipine group. Larger %-drop in uric acid levels were associated with larger %-reduction of LAVI (p < 0.01). L- and N-type calcium channel blocker but not L-type calcium channel blocker may improve LV diastolic function in hypertensive patients, at least partially through the decrease in uric acid levels.
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Effects of the lercanidipine-enalapril combination vs. the corresponding monotherapies on home blood pressure in hypertension: evidence from a large database.
Mancia, G, Omboni, S, Chazova, I, Coca, A, Girerd, X, Haller, H, Parati, G, Pauletto, P, Pupek-Musialik, D, Svyshchenko, Y, et al
Journal of hypertension. 2016;(1):139-48
Abstract
OBJECTIVE To compare a combination of a dihydropyridine calcium-channel blocker with an angiotensin converting enzyme inhibitor vs. monotherapy with one or the other drug and placebo for their effects on home blood pressure (HBP). METHODS After a 2-week placebo wash-out, patients with an elevated office blood pressure (BP) (diastolic 100-109 and systolic <180 mmHg) and HBP (diastolic ≥85 mmHg) were randomized double-blind to a 10-week treatment with placebo, lercanidipine, 10 or 20 mg daily, enalapril, 10 or 20 mg daily, or the four possible combinations. In addition to office BP, HBP was self-measured via a validated semiautomatic device twice in the morning and twice in the evening during the 7 days before randomization and at the end of treatment. Baseline and treatment HBP values were separately averaged for each day, morning, evening or the whole monitoring period, excluding the first day. Day-by-day HBP variability was defined as the SD or the variation coefficient of the daily BP averages. RESULTS Eight hundred and fifty-four patients with valid HBP recordings at baseline and at the end of treatment were analyzed (intention-to-treat population). From the baseline value (147.0±11.6 mmHg) systolic/diastolic HBP showed a small reduction (average baseline-adjusted change: -1.8/-1.6 mmHg) with placebo, a more marked significant fall with monotherapies (-8.8/-5.9 mmHg, P < 0.001/<0.001 vs. placebo) and even more with combination treatment (11.6/-7.6 mmHg, P < 0.001/ < 0.001 vs. placebo and P < 0.01/ < 0.05 vs. monotherapy). A similar pattern was observed for each of the days of the BP self-monitoring period as well as for either morning or evening values, although the difference between mono and combination treatment appeared to be consistently significant for the morning values only. Day-by-day systolic BP-SD was unaffected by placebo and slightly reduced by drug treatments, with no, however, significant changes in SBP-variation coefficient. Baseline and end of treatment HBP values showed a limited correlation with office BP values, this being particularly the case for treatment-induced changes (correlation coefficients: 0.37 for systolic and 0.45 for diastolic BP). CONCLUSION This large HBP database shows that the lercanidipine-enalapril combination lowers HBP more effectively than the corresponding monotherapies and placebo, and that this greater effect is consistent between days. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT01093807.
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Improvements in Augmentation Index and Urinary Albumin Excretion With Benidipine in Hypertensive Patients With Chronic Kidney Disease.
Takayama, T, Yoda, S, Yajima, Y, Kasamaki, Y, Kunimoto, S, Kanai, T, Hirayama, A
International heart journal. 2016;(1):53-60
Abstract
Although calcium channel blockers (CCB) are expected to improve the augmentation index (AI) in CKD patients, the potential effect of benidipine on AI has been poorly studied.The present study aimed to compare the effect of benidipine and amlodipine in the treatment of CKD patients as measured through AI and urinary albumin excretion (UAE). Eligible patients with CKD were randomized to either the benidipine group or amlodipine group. Changes in UAE and AI were compared with target blood pressure level set at < 130/80 mmHg. A total of 108 patients were enrolled; 88 patients who were followed up were included in the analysis. Although no significant change in renal function was noted in either group, there was a significant improvement in AI only in the benidipine group (85.7 ± 13.3% to 81.4 ± 15.2%; P = 0.021) A subgroup analysis of 64 patients who achieved SBP < 140 mmHg at the end of follow-up (31 on amlodipine and 33 on benidipine) was carried out. Significant improvement in AI was noted only in the benidipine group (84.5 ± 13.6% to 79.5 ± 15.2%; P = 0.0138). In another subgroup of patients with UAE ≥ 300 mg/g Cr, a significant improvement in UAE in the benidipine group was found compared with the amlodipine group (-25 ± 46, 51 ± 60%, P = 0.031, respectively).These results suggest that benidipine might reduce significantly AI and might have potentially greater improvements in UAE than amlodipine in advanced CKD patients receiving RAS inhibitors.
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Enalapril/lercanidipine combination on markers of cardiovascular risk: a randomized study.
Derosa, G, Bonaventura, A, Romano, D, Bianchi, L, Fogari, E, D'Angelo, A, Maffioli, P
Journal of the American Society of Hypertension : JASH. 2014;(6):422-8
Abstract
The aim of this study was to evaluate enalapril/lercanidipine combination effects on markers of cardiovascular risk stratification in hypertensive patients. A total of 359 patients were randomized to enalapril 20 mg, lercanidipine 10 mg, or enalapril/lercanidipine 20/10 mg fixed combination. We evaluated blood pressure (BP), fasting plasma glucose (FPG), lipid profile, lipoprotein(a) (Lp[a]), soluble receptor for advanced glycation end products (sRAGE), soluble CD40 ligand (sCD40 L), serum myeloperoxidase (MPO), high sensitivity C-reactive protein (Hs-CRP), and tumor necrosis factor-α (TNF-α). We recorded a decrease of BP in all groups, with the enalapril/lercanidipine combination being more effective in reducing BP compared with single monotherapies. Lipid profile or FPG were not affected by various treatments. Lercanidipine, but not enalapril, improved Lp(a) levels compared with baseline, with enalapril/lercanidipine having a greater effect on Lp(a) reduction. All treatments increased sRAGE levels, and decreased sCD40 L and MPO, even if enalapril/lercanidipine combination was more effective than single monotherapies. TNF-α and Hs-CRP were greater reduced by enalapril/lercanidipine combination compared with enalapril (P < .05 for both). The enalapril/lercanidipine fixed combination was more effective than single monotherapies in decreasing BP, but also in improving markers of cardiovascular risk stratification in hypertensive patients.
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Impact of azelnidipine and amlodipine on left ventricular mass and longitudinal function in hypertensive patients with left ventricular hypertrophy.
Motoki, H, Koyama, J, Izawa, A, Tomita, T, Miyashita, Y, Takahashi, M, Ikeda, U
Echocardiography (Mount Kisco, N.Y.). 2014;(10):1230-8
Abstract
BACKGROUND The impact of long-acting calcium channel blocker (CCB) administration on serial changes in left ventricular (LV) function and morphology in hypertensive patients with LV hypertrophy remains unclear. This study attempted to clarify this impact by comparing the effects of administration of azelnidipine with that of amlodipine using conventional and speckle tracking echocardiography. METHODS An equal number (16) of 32 hypertensive patients was prospectively assigned to a group administered 5 mg of amlodipine/day or a group administered 16 mg of azelnidipine/day. LV function and morphology was examined by conventional and speckle tracking echocardiography at baseline and at 1, 3, 6, and 12 months after treatment initiation. RESULTS Both groups were found to have experienced a significant decrease in systolic blood pressure by 1 month after treatment initiation; a significant reduction in septal thickness and LV mass index at 6 and 12 months. Transmitral flow E/A ratio and early diastolic mitral annular velocity at lateral wall significantly improved at 12 months. On the other hand, a significant improvement of global longitudinal strain was observed earlier than the above indexes at 3, 6, and 12 months. Ar-A duration difference was significantly decreased at 3 months. The global circumferential strain improved significantly at 3 months, but there were no significant changes in mid-/apical circumferential and radial strains throughout the study period. CONCLUSION Azelnidipine has beneficial effects on LV mass regression, transmitral flow, tissue Doppler, and LV longitudinal strain that are comparable to those of amlodipine on the same parameters.