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A randomized controlled trial on the blood pressure-lowering effect of amlodipine and nifedipine-GITS in sustained hypertension.
Huang, QF, Sheng, CS, Li, Y, Dou, Y, Zheng, MS, Zhu, ZM, Wang, JG, ,
Journal of clinical hypertension (Greenwich, Conn.). 2019;(5):648-657
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Abstract
In a multicenter, randomized trial, we investigated whether the long half-time dihydropyridine calcium channel blocker amlodipine was more efficacious than the gastrointestinal therapeutic system (GITS) formulation of nifedipine in lowering ambulatory blood pressure (BP) in sustained hypertension (clinic systolic/diastolic BP 140-179/90-109 mm Hg and 24-hour systolic/diastolic BP ≥ 130/80 mm Hg). Eligible patients were randomly assigned to amlodipine 5-10 mg/day or nifedipine-GITS 30-60 mg/day. Ambulatory BP monitoring was performed for 24 hours at baseline and 4-week treatment and for 48 hours at 8-week treatment with a dose of medication missed on the second day. After 8-week treatment, BP was similarly reduced in the amlodipine (n = 257) and nifedipine-GITS groups (n = 248) for both clinic and ambulatory (24-hour systolic/diastolic BP 10.3/6.5 vs 10.9/6.3 mm Hg, P ≥ 0.24) measurements. However, after missing a dose of medication, ambulatory BP reductions were greater in the amlodipine than nifedipine-GITS group, with a significant (P ≤ 0.04) between-group difference in 24-hour (-1.2 mm Hg) and daytime diastolic BP (-1.5 mm Hg). In conclusion, amlodipine and nifedipine-GITS were efficacious in reducing 24-hour BP. When a dose of medication was missed, amlodipine became more efficacious than nifedipine-GITS.
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Endothelin Receptor Antagonism Improves Lipid Profiles and Lowers PCSK9 (Proprotein Convertase Subtilisin/Kexin Type 9) in Patients With Chronic Kidney Disease.
Farrah, TE, Anand, A, Gallacher, PJ, Kimmitt, R, Carter, E, Dear, JW, Mills, NL, Webb, DJ, Dhaun, N
Hypertension (Dallas, Tex. : 1979). 2019;(2):323-330
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Abstract
Dyslipidemia is common in chronic kidney disease (CKD). Despite statins, many patients fail to adequately lower lipids and remain at increased risk of cardiovascular disease. Selective ETA (endothelin-A) receptor antagonists reduce cardiovascular disease risk factors. Preclinical data suggest that ETA antagonism has beneficial effects on circulating lipids. We assessed the effects of selective ETA antagonism on circulating lipids and PCSK9 (proprotein convertase subtilisin/kexin type 9) in CKD. This was a secondary analysis of a fully randomized, double-blind, 3-phase crossover study. Twenty-seven subjects with predialysis CKD on optimal cardio- and renoprotective treatment were randomly assigned to receive 6 weeks dosing with placebo, the selective ETA receptor antagonist, sitaxentan, or long-acting nifedipine. We measured circulating lipids and PCSK9 at baseline and then after 3 and 6 weeks. Baseline lipids and PCSK9 did not differ before each study phase. Whereas placebo and nifedipine had no effect on lipids, 6 weeks of ETA antagonism significantly reduced total (-11±1%) and low-density lipoprotein-associated (-20±3%) cholesterol, lipoprotein (a) (-16±2%) and triglycerides (-20±4%); high-density lipoprotein-associated cholesterol increased (+14±2%), P<0.05 versus baseline for all. Additionally, ETA receptor antagonism, but neither placebo nor nifedipine, reduced circulating PCSK9 (-19±2%; P<0.001 versus baseline; P<0.05 versus nifedipine and placebo). These effects were independent of statin use and changes in blood pressure or proteinuria. Selective ETA antagonism improves lipid profiles in optimally-managed patients with CKD, effects that may occur through a reduction in circulating PCSK9. ETA receptor antagonism offers a potentially novel strategy to reduce cardiovascular disease risk in CKD. Clinical Trial Registration- URL: http://www.clinicaltrials.gov . Unique identifier: NCT00810732.
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Blood pressure-lowering effects of nifedipine/candesartan combinations in high-risk individuals: subgroup analysis of the DISTINCT randomised trial.
Mancia, G, Cha, G, Gil-Extremera, B, Harvey, P, Lewin, AJ, Villa, G, Kjeldsen, SE
Journal of human hypertension. 2017;(3):178-188
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Abstract
The DISTINCT study (reDefining Intervention with Studies Testing Innovative Nifedipine GITS-Candesartan Therapy) investigated the efficacy and safety of nifedipine GITS/candesartan cilexetil combinations vs respective monotherapies and placebo in patients with hypertension. This descriptive sub-analysis examined blood pressure (BP)-lowering effects in high-risk participants, including those with renal impairment (estimated glomerular filtration rate<90 ml min-1, n=422), type 2 diabetes mellitus (n=202), hypercholesterolaemia (n=206) and cardiovascular (CV) risk factors (n=971), as well as the impact of gender, age and body mass index (BMI). Participants with grade I/II hypertension were randomised to treatment with nifedipine GITS (N) 20, 30, 60 mg and/or candesartan cilexetil (C) 4, 8, 16, 32 mg or placebo for 8 weeks. Mean systolic BP and diastolic BP reductions after treatment in high-risk participants were greater, overall, with N/C combinations vs respective monotherapies or placebo, with indicators of a dose-response effect. Highest rates of BP control (ESH/ESC 2013 guideline criteria) were also achieved with highest doses of N/C combinations in each high-risk subgroup. The benefits of combination therapy vs monotherapy were additionally observed in patient subgroups categorised by gender, age or BMI. All high-risk participants reported fewer vasodilatory adverse events in the pooled N/C combination therapy than the N monotherapy group. In conclusion, consistent with the DISTINCT main study outcomes, high-risk participants showed greater reductions in BP and higher control rates with N/C combinations compared with respective monotherapies and lesser vasodilatory side-effects compared with N monotherapy.
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[Management of ureteric colic with ketorolac and nifedipin vs. ketorolac and tamsulosin in the emergency room].
Montiel-Jarquín, ÁJ, Rocha-Rocha, VM, Solís-Mendoza, HA, Romero-Figueroa, MS, Etchegaray-Morales, I, Alvarado-Ortega, I
Revista medica del Instituto Mexicano del Seguro Social. 2017;:S20-S25
Abstract
BACKGROUND Ureteric colic is the most common symptom of lithiasis. It is caused by the presence of stones accumulated in the renal papillae. These stones often migrate down the ureter, causing a ureteric colic, characterized by a severe pain in the lumbar region. The aim of this study was to compare the use of ketorolac and nifedipine vs. ketorolac and tamsulosin for the medical treatment of pain caused by stones in the lower ureter. METHODS Longitudinal study of 150 patients of 21-years or older with stones in the lower third of the ureter. 50% received ketorolac and nifedipine and the other 50%, ketorolac and tamsulosin. The Numeric Pain Rating Scale (NPRS) was used for the assessment of pain at admission and 4 and 12 hours after the treatment was administered. We used descriptive and inferential statistics (Mann-Whitney-Wilcoxon, chi-squared and Poisson regression). RESULTS Mean age was 38.17 years; 54.7% were male and 45.3% female. NPRS mean was 9.69 (initially), 7.42 (at 4 hours) and 2.05 (at 12 hours). There were no significant differences in the initial measurement of pain between groups (p < 0.005); four and 12 hours later the pain decreased more in patients managed with ketorolac and nifedipine, p = 0.0041. There were no complications nor side effects in both treatments. CONCLUSION The use of ketorolac and nifedipine is more effective than the use of ketorolac and tamsulosin for the management of pain caused by lower ureteral colic during the first 12 hours of treatment.
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White coat effect in hypertensive patients: the role of hospital environment or physician presence.
Wang, XX, Shuai, W, Peng, Q, Li, JX, Li, P, Cheng, XS, Su, H
Journal of the American Society of Hypertension : JASH. 2017;(8):498-502
Abstract
This study was to evaluate the role of hospital environment or physician presence for white coat effect (WCE) in hypertensive patients. At first, 54 hypertensive outpatients diagnosed on office blood pressure (OBP) were included for 2-week placebo run in. During the second week of the run in period, home BP was measured using electronic BP monitors for 5-7 days. Finally, 26 sustained hypertensive patients with home systolic BP/diastolic BP over 135/85 (but <180/110) mm Hg were enrolled for 8-week treatment of nifedipine controlled-release tablet. In the visit day, BP was measured by patient-self (OBP-p) or by doctor (OBP-d) according to order determined with randomization method. The self-BP measurement was performed in a reception room of hospital. The differences between home BP and OBP-d or OBP-p were calculated as WCE calculated on doctor-measurement (WCE-d) or WCE calculated on patient-measurement (WCE-p), respectively. The home and OBP were measured with the same BP device for each patient during the study period. In the total 54 outpatients received placebo, the WCE-d was similar to the WCE-p (for systolic BP 6.6 ± 14.4 vs. 6.8 ± 15.8 mm Hg, NS; for diastolic BP 3.3 ± 8.8 vs. 2.9 ± 9.2 mm Hg, NS). Meanwhile, the 26 sustained hypertensive patients had similar systolic WCE-d and WCE-p (4.8 ± 10.3 vs. 5.0 ± 12.2 mm Hg, NS) at placebo stage. Similarly, these values were comparable (3.0 ± 14.0 vs. 2.2 ± 14.4 mm Hg, NS) in treatment stage. Hospital environment plays a main role for the WCE in hypertensive patients.
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Nifedipine GITS/Candesartan Combination Therapy Lowers Blood Pressure Across Different Baseline Systolic and Diastolic Blood Pressure Categories: DISTINCT Study Subanalyses.
Kjeldsen, SE, Cha, G, Villa, G, Mancia, G, ,
Journal of clinical pharmacology. 2016;(9):1120-9
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DISTINCT was an 8-week, double-blind, randomized study to investigate the antihypertensive efficacy and safety of various nifedipine gastrointestinal treatment system (GITS)/candesartan cilexetil (N/C) dose combinations, vs respective monotherapies or placebo, in patients with diastolic blood pressure (DBP) ≥95 to <110 mm Hg. The current prespecified analysis compared BP reduction in participants with mild vs moderate baseline hypertension (ie, systolic [S]BP <160 mm Hg vs ≥160 mm Hg and DBP <100 mm Hg vs ≥100 mm Hg). A total of 1362 patients were analyzed by descriptive statistics. In all patient subgroups investigated, the NC combinations (ie, N: 20, 30, or 60 mg; C: 4, 8, 16, or 32 mg daily) provided greater SBP and DBP lowering and higher rates of BP control (defined as BP <140/90 mm Hg) than respective monotherapies or placebo, with greatest absolute BP reductions observed in the moderately elevated SBP or DBP subgroups. A trend to dose-response relationship was observed in each subgroup. In each SBP and DBP subgroup, treatment-related vasodilatory events (flushing, headache, or edema) were less frequent for patients receiving NC combination therapy than N monotherapy. These analyses support the use of calcium antagonist and angiotensin receptor blocker combination therapy in patients with both mild and moderate hypertension, for whom effective BP normalization and good drug tolerance would greatly reduce the risk of cardiovascular events.
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RETRACTED: Nicorandil vs nifedipine for the treatment of preterm labour: a randomized clinical trial.
Rezk, M, Sayyed, T, Masood, A, Dawood, R
European journal of obstetrics, gynecology, and reproductive biology. 2015;:27-30
Abstract
This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the Editor-in-Chief. The editors were alerted to the following concerning features of this trial: The submission date is impossible. Patients were recruited at 24 to 34 weeks (mean 31 w). 18% of participants delivered after 37 weeks. Average recruitment 26 per month. Recruitment ended September 2014 but the paper was received by journal on 23 October 2014. The second author, Sayyed T, is co-author of related retracted papers in BJOG. In view of these concerns we wrote to Dr Rezk who had no satisfactory explanation and declined to share the data. We have therefore decided to retract.
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Medical expulsive therapy in adults with ureteric colic: a multicentre, randomised, placebo-controlled trial.
Pickard, R, Starr, K, MacLennan, G, Lam, T, Thomas, R, Burr, J, McPherson, G, McDonald, A, Anson, K, N'Dow, J, et al
Lancet (London, England). 2015;(9991):341-9
Abstract
BACKGROUND Meta-analyses of previous randomised controlled trials concluded that the smooth muscle relaxant drugs tamsulosin and nifedipine assisted stone passage for people managed expectantly for ureteric colic, but emphasised the need for high-quality trials with wide inclusion criteria. We aimed to fulfil this need by testing effectiveness of these drugs in a standard clinical care setting. METHODS For this multicentre, randomised, placebo-controlled trial, we recruited adults (aged 18-65 years) undergoing expectant management for a single ureteric stone identified by CT at 24 UK hospitals. Participants were randomly assigned by a remote randomisation system to tamsulosin 400 μg, nifedipine 30 mg, or placebo taken daily for up to 4 weeks, using an algorithm with centre, stone size (≤5 mm or >5 mm), and stone location (upper, mid, or lower ureter) as minimisation covariates. Participants, clinicians, and trial personnel were masked to treatment assignment. The primary outcome was the proportion of participants who did not need further intervention for stone clearance within 4 weeks of randomisation, analysed in a modified intention-to-treat population defined as all eligible patients for whom we had primary outcome data. This trial is registered with the European Clinical Trials Database, EudraCT number 2010-019469-26, and as an International Standard Randomised Controlled Trial, number 69423238. FINDINGS Between Jan 11, 2011, and Dec 20, 2013, we randomly assigned 1167 participants, 1136 (97%) of whom were included in the primary analysis (17 were excluded because of ineligibility and 14 participants were lost to follow-up). 303 (80%) of 379 participants in the placebo group did not need further intervention by 4 weeks, compared with 307 (81%) of 378 in the tamsulosin group (adjusted risk difference 1·3% [95% CI -5·7 to 8·3]; p=0·73) and 304 (80%) of 379 in the nifedipine group (0·5% [-5·6 to 6·5]; p=0·88). No difference was noted between active treatment and placebo (p=0·78), or between tamsulosin and nifedipine (p=0·77). Serious adverse events were reported in three participants in the nifedipine group (one had right loin pain, diarrhoea, and vomiting; one had malaise, headache, and chest pain; and one had severe chest pain, difficulty breathing, and left arm pain) and in one participant in the placebo group (headache, dizziness, lightheadedness, and chronic abdominal pain). INTERPRETATION Tamsulosin 400 μg and nifedipine 30 mg are not effective at decreasing the need for further treatment to achieve stone clearance in 4 weeks for patients with expectantly managed ureteric colic. FUNDING UK National Institute for Health Research Health Technology Assessment Programme.
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Human lymphatic vessel contractile activity is inhibited in vitro but not in vivo by the calcium channel blocker nifedipine.
Telinius, N, Mohanakumar, S, Majgaard, J, Kim, S, Pilegaard, H, Pahle, E, Nielsen, J, de Leval, M, Aalkjaer, C, Hjortdal, V, et al
The Journal of physiology. 2014;(21):4697-714
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Calcium channel blockers (CCB) are widely prescribed anti-hypertensive agents. The commonest side-effect, peripheral oedema, is attributed to a larger arterial than venous dilatation causing increased fluid filtration. Whether CCB treatment is detrimental to human lymphatic vessel function and thereby exacerbates oedema formation is unknown. We observed that spontaneous lymphatic contractions in isolated human vessels (thoracic duct and mesenteric lymphatics) maintained under isometric conditions were inhibited by therapeutic concentrations (nanomolar) of the CCB nifedipine while higher than therapeutic concentrations of verapamil (micromolar) were necessary to inhibit activity. Nifedipine also inhibited spontaneous action potentials measured by sharp microelectrodes. Furthermore, noradrenaline did not elicit normal increases in lymphatic vessel tone when maximal constriction was reduced to 29.4 ± 4.9% of control in the presence of 20 nmol l(-1) nifedipine. Transcripts for the L-type calcium channel gene CACNA1C were consistently detected from human thoracic duct samples examined and the CaV1.2 protein was localized by immunoreactivity to lymphatic smooth muscle cells. While human lymphatics ex vivo were highly sensitive to nifedipine, this was not apparent in vivo when nifedipine was compared to placebo in a randomized, double-blinded clinical trial: conversely, lymphatic vessel contraction frequency was increased and refill time was faster despite all subjects achieving target nifedipine plasma concentrations. We conclude that human lymphatic vessels are highly sensitive to nifedipine in vitro but that care must be taken when extrapolating in vitro observations of lymphatic vessel function to the clinical situation, as similar changes in lymphatic function were not evident in our clinical trial comparing nifedipine treatment to placebo.
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Randomized trial comparing the effects of a low-dose combination of nifedipine GITS and valsartan versus high-dose monotherapy on central hemodynamics in patients with inadequately controlled hypertension: FOCUS study.
Park, JB, Ha, JW, Jung, HO, Rhee, MY, ,
Blood pressure monitoring. 2014;(5):294-301
Abstract
OBJECTIVES Measurement of central blood pressure provides prognostic information beyond conventional peripheral blood pressure (BP). However, few studies have directly compared the effects of antihypertensives on central hemodynamics. This study investigated the effects of a low-dose combination of nifedipine Gastrointestinal Therapeutic System (GITS) and valsartan versus high-dose monotherapy with either agent in reducing central BP in essential hypertension inadequately controlled by low-dose monotherapy. MATERIALS AND METHODS In this prospective, open-label, randomized, active-controlled, multicenter 8-week study, patients not meeting the target BP after 4 weeks of treatment with low-dose monotherapy were randomized to receive nifedipine GITS 30 mg plus valsartan 80 mg (N30+V80), nifedipine GITS 60 mg (N60), or valsartan 160 mg (V160) for a further 4 weeks. Central hemodynamics were measured by applanation tonometry. RESULTS A total of 391 patients were enrolled. Reduction in central systolic BP from baseline to week 8, the primary efficacy variable, was significantly greater in the N30+V80 group (-27.2±14.7 mmHg) and the N60 group (-27.1±16.5 mmHg) compared with V160 group (-14.4±16.6 mmHg). Decrease in the augmentation index in the N60 group was significantly greater compared with V160 alone, without differences between combination therapy and either high-dose monotherapy. Decreases in brachial systolic BP were significantly greater in the N30+V80 and N60 groups than in the V160 group. By multiple regression analysis, most differences in drug effects on central hemodynamics disappeared after controlling for changes in peripheral BP. A low rate of adverse events occurred in all treatment groups. CONCLUSION A low-dose combination of nifedipine GITS plus valsartan or high-dose nifedipine was more effective in improving central hemodynamics than high-dose valsartan in patients with hypertension, mostly because of the improvement in peripheral (brachial) hemodynamics.