BACKGROUNDCombination of angiotensin-converting enzyme inhibitors and calcium channel blockers has been successfully used in the antihypertensive therapy for many years. Fixed dose combinations of ramipril/amlodipine have a benefit effect for patients to achieve target blood pressure (BP). This study aimed to assess the efficacy and safety of fixed dose combinations of ramipril and amlodipine (Egiramlon®) in hypertensive diabetic patients.

METHODSHypertensive diabetic patients who were enrolled into the RAMONA trial were included in this open, prospective, Phase IV observational clinical study. Patients had mild-to-moderate hypertension and failed to reach target BP levels through their previous therapy. During the four months of observation, patients took part in three visits (1st day = visit 1, 1st month = visit 2, and 4th month = visit 3) where they received a fixed dose combination of 5/5, 5/10, 10/5, or 10/10 mg ramipril/amlodipine, respectively, with the possibly required dose titrations, based on the decision of their attending physician. Target BP for diabetic patients was <140/85 mmHg. BP levels were measured in all visits, by taking two readings at 2-min interval. Laboratory tests including full blood count, renal function test, electrolytes, blood glucose, serum cholesterol, uric acid, triglycerides, liver function test, creatinine kinase, and midstream urinalysis were performed at visit 1 and visit 3.

RESULTSThe 6423 patients completed the study. Among these patients, 1276 (19.9%) patients suffered from type 2 diabetes mellitus. The mean age of these diabetic patients was 64.2 ± 10.0 years; 707 (55.4%) patients were males. Target BP was achieved by 891 (69.8%) of diabetic patients at visit 3 (primary endpoint). BP decreased from 157.5/91.3 ± 9.6/7.6 mmHg (visit 1) to 130.9/79.6 ± 7.4/5.8 mmHg (visit 3). As for the secondary endpoint of the study, total cholesterol decreased from 5.50 ± 1.13 mmol/L (visit 1) to 5.20 ± 0.95 mmol/L (P = 0.000), low-density lipoprotein cholesterol decreased from 3.20 ± 0.93 mmol/L to 3.00 ± 0.77 mmol/L (P = 0.000), triglyceride decreased from 2.20 ± 1.14 mmol/L to 2.00 ± 1.97 mmol/L (P = 0.000), while high-density lipoprotein cholesterol increased from 1.30 ± 0.42 to 1.35 ± 0.30 mmol/L (P = 0.001) until the end of the 4th month (visit 3). Fasting blood glucose of the hypertensive diabetic patients decreased from 7.20 ± 1.88 mmol/L to 6.70 ± 1.38 mmol/L (P = 0.000), while HbA1c decreased from 7.90 ± 1.78% to 7.60 ± 1.83% (P = 0.000). Various fixed dose combinations of ramipril/amlodipine were well tolerated and no adverse event related to the use of the medicine has appeared.

CONCLUSIONSThe fixed dose combination of ramipril/amlodipine was effective in hypertensive diabetic patients who failed to reach target BP previously.

Aged ; Amlodipine ; administration & dosage ; therapeutic use ; Angiotensin-Converting Enzyme Inhibitors ; administration & dosage ; therapeutic use ; Antihypertensive Agents ; administration & dosage ; therapeutic use ; Blood Pressure ; drug effects ; Diabetes Mellitus, Type 2 ; drug therapy ; Female ; Humans ; Hypertension ; drug therapy ; Male ; Middle Aged ; Ramipril ; administration & dosage ; therapeutic use

BACKGROUNDG-protein β-polypeptide 3 (GNB3) is a β subunit isoform of G-protein that plays important role in signal transduction of membrane G-protein coupled receptors (GPCRs). The GNB3 splice variant C825T (rs5443) is associated with risk for essential hypertension (EH) and efficacy of therapeutic drugs targeting GPCRs. It is unknown whether the polymorphism is associated with blood pressure (BP) response to telmisartan or amlodipine, two widely prescribed antihypertensive drugs.

METHODSA total of 93 subjects initially diagnosed as EH were recruited and underwent a 4-week treatment with telmisartan (42 patients) or amlodipine (51 patients) monotherapy. Both baseline and after-treatment BP were measured. GNB3 C825T polymorphism was genotyped by polymerase chain reaction-restriction fragment length polymorphism.

RESULTSBaseline systolic BP (SBP) and diastolic BP (DBP) were comparable among C825T genotypes in both telmisartan and amlodipine treatment groups. Patients with the CT or TT genotypes showed significantly lower body mass index (BMI) as compared with CC homozygotes in both groups (P < 0.05, respectively). GNB3 825TT homozygotes showed significantly higher after-treatment DBP and mean arterial pressure (MAP) than those carrying at least one 825C allele (P < 0.01) in the telmisartan treatment group. No difference in after-treatment SBP, DBP, and MAP levels among C825T genotypes was observed in the amlodipine treatment group. No significant difference in absolute changes in BP levels was observed among the genotypes in either treatment group.

CONCLUSIONThe GNB3 C825T splice variant is associated with the DBP-lowering effect of telmisartan but not amlodipine in Chinese EH patients.

Adult ; Aged ; Amlodipine ; therapeutic use ; Antihypertensive Agents ; therapeutic use ; Benzimidazoles ; therapeutic use ; Benzoates ; therapeutic use ; Blood Pressure ; drug effects ; Essential Hypertension ; Female ; Genotype ; Heterotrimeric GTP-Binding Proteins ; genetics ; Humans ; Hypertension ; drug therapy ; genetics ; Male ; Middle Aged ; Polymorphism, Genetic ; genetics ; Polymorphism, Restriction Fragment Length ; genetics

Adult ; Aged ; Amlodipine ; adverse effects ; Drug Overdose ; diagnostic imaging ; drug therapy ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Male ; Middle Aged ; Radiography, Thoracic ; Treatment Outcome

BACKGROUND/AIMS: This meta-analysis compared the effects of amlodipine besylate, a charged dihydropyridine-type calcium channel blocker (CCB), with other non-CCB antihypertensive therapies regarding the cardiovascular outcome. METHODS: Data from seven long-term outcome trials comparing the cardiovascular outcomes of an amlodipine-based regimen with other active regimens were pooled and analyzed. RESULTS: The risk of myocardial infarction was significantly decreased with an amlodipine-based regimen compared with a non-CCB-based regimen (odds ratio [OR], 0.91; 95% confidence interval [CI], 0.84 to 0.99; p = 0.03). The risk of stroke was also significantly decreased (OR, 0.84; 95% CI, 0.79 to 0.90; p < 0.00001). The risk of heart failure increased slightly with marginal significance for an amlodipine-based regimen compared with a non-CCB-based regimen (OR, 1.14; 95% CI, 0.98 to 1.31; p = 0.08). However, when compared overall with beta-blockers and diuretics, amlodipine showed a comparable risk. Amlodipine-based regimens demonstrated a 10% risk reduction in overall cardiovascular events (OR, 0.90; 95% CI, 0.82 to 0.99; p = 0.02) and total mortality (OR, 0.95; 95% CI, 0.91 to 0.99; p = 0.01). CONCLUSIONS: Amlodipine reduced the risk of total cardiovascular events as well as all-cause mortality compared with non-CCB-based regimens, indicating its benefit for high-risk cardiac patients.
Amlodipine/*therapeutic use ; Antihypertensive Agents/*therapeutic use ; Blood Pressure/*drug effects ; Calcium Channel Blockers/*therapeutic use ; Chi-Square Distribution ; Clinical Trials as Topic ; Heart Failure/etiology/mortality/*prevention & control ; Humans ; Hypertension/complications/diagnosis/*drug therapy/mortality/physiopathology ; Myocardial Infarction/etiology/mortality/*prevention & control ; Odds Ratio ; Risk Factors ; Stroke/etiology/mortality/*prevention & control ; Treatment Outcome

No abstract available.
Amlodipine/*therapeutic use ; Antihypertensive Agents/*therapeutic use ; Blood Pressure/*drug effects ; Calcium Channel Blockers/*therapeutic use ; Heart Failure/*prevention & control ; Humans ; Hypertension/*drug therapy ; Myocardial Infarction/*prevention & control ; Stroke/*prevention & control

OBJECTIVETo evaluate the protective effect of amlodipine against contrast agent-induced renal injury in elderly patients with coronary heart disease.

METHODSA total of 189 elderly patients (>60 years) with coronary heart disease undergoing coronary artery angiography were randomly assigned into amlodipine group and control group to receive amlodipine or placebo, respectively, before and after administration of the contrast agent. At 24 h, 48 h and 5 days after contrast agent administration, the parameters of renal function were measured including serum cystatin C, urea nitrogen, creatinine, creatinine clearance rate, urine β2-microglobulin, and urine N-acetyl-β-glucosaminidase.

RESULTSIn both groups, the contrast agents obviously affected the renal functions of the patients (P<0.05). At 24 h after contrast administration, the levels of serum cystatin C, urine β2-microglobulin and urine NAG were significantly lower in amlodipine group than in the control group, but the other functional parameters showed no significant difference. At 48 h after contrast administration, the glomerular and tubular functional parameters were all superior in amlodipine group (P<0.05). At 5 days, the two groups showed significant differences in such glomerular and tubular functional parameters as urea nitrogen, creatinine, creatinine clearance rate, urine β2-microglobulin, and urine NAG (P<0.05), but not in serum cystatin C level. The incidence of contrast agent-induced nephropathy was significantly lower in amlodipine group than in the control group (5/95 vs 10/94, P<0.05).

CONCLUSIONSAmlodipine offers protection against radiographic contrast agent-induced renal injury in elderly patients with coronary heart disease.

Aged ; Amlodipine ; pharmacology ; therapeutic use ; Contrast Media ; adverse effects ; pharmacology ; Coronary Angiography ; Coronary Disease ; diagnostic imaging ; Female ; Humans ; Kidney Diseases ; chemically induced ; drug therapy ; Kidney Function Tests ; Male ; Middle Aged

OBJECTIVETo investigate the effects and safety of Western medicine combined with Chinese medicine (CM) based on syndrome differentiation in the treatment of elderly polarized hypertension (PHPT), or isolated systolic hypertension with low diastolic blood pressure (DBP).

METHODSA total of 125 elderly patients with PHPT were randomly assigned to two groups: 59 in the control group treated by Western medicine and 66 in the intervention group treated by Western medicine combined with CM treatment. Based on syndrome differentiation, the patients in the intervention group were further divided into subgroups of yang-qi deficiency and yin-qi deficiency. All subjects were treated with Western medicine of Amlodipine Besylate Tablets and Irbesartan Tablets (or Irbesartan and Hydrochlorothiazide Tablets), to decrease their systolic blood pressure (SBP) slowly to 125-135 mm Hg in 2-6 weeks. In the intervention group, Shiyiwei Shenqi Capsule was given additionally to the subgroup of yang-qi deficiency at the dosage of 3-5 capsules, thrice a day, while Dengzhan Shengmai Capsule was given additionally to the subgroup of yin-qi deficiency at the dosage of 2 capsules, 2-3 times per day. For all subjects, SBP, pulse pressure (PP), and DBP were measured before treatment and at the terminal of a 6-week treatment. For subjects in the intervention group, left ventricular ejection fraction (LVEF) was also recorded.

RESULTSAfter a 6-week treatment, the SBP in the two groups and the PP in the intervention group decreased significantly compared to those before treatment (P<0.05), while the PP in the control group showed no significant difference between prior and post-treatment (P>0.05). After treatment, the DBP in the control group decreased (P>0.05), while the DBP and LVEF in the intervention group showed an increase tendency although it had no statistical significance (P>0.05). When subjects in the intervention group were classified further by the course of disease, the DBP and LVEF of subjects whose course of disease were less than 2 years, increased significantly after treatment (P<0.05).

CONCLUSIONWestern medicine combined with CM treatment based on syndrome differentiation was safer and more effective than Western medicine alone in the treatment of elderly PHPT, because it not only reduced SBP but also improved DBP, which might lower the incidence of the cardiovascular and cerebrovascular events.

Aged ; Amlodipine ; adverse effects ; pharmacology ; therapeutic use ; Antihypertensive Agents ; adverse effects ; pharmacology ; therapeutic use ; Biphenyl Compounds ; adverse effects ; pharmacology ; therapeutic use ; Blood Pressure ; drug effects ; Diastole ; drug effects ; Drugs, Chinese Herbal ; adverse effects ; pharmacology ; therapeutic use ; Female ; Humans ; Hypertension ; drug therapy ; physiopathology ; Male ; Stroke Volume ; drug effects ; Syndrome ; Tetrazoles ; adverse effects ; pharmacology ; therapeutic use

OBJECTIVETo observe the therapeutic effect of calming the liver and restraining the Yang formula in treating patients with mild or moderate degree of essential hypertension (syndrome of hyperactivity of liver-Yang), and to explore its mechanism in lowering blood pressure.

METHODThe 348 patients with EH of stage I , II were randomly divided into two groups, the 174 patients in the treated group were treated with the calming the liver and restraining the Yang formula, and the 174 patients in the control group were treated with amlodipine. The treatment course for them all was 12 weeks. The related clincial symptoms score and quality of life score estimated before and after treatment at 4th week, 8th week and 12th week were observed. Before and after treatment, the ambulatory blood pressure (AMBP), heart rate, blood lipid, serum livels of high-sensitivity C-reactive protein (Hs-CRP), Angiotensin-II (Ang II) and calcitonin gene-related peptide (CGRP) were measured respectively in 40 patients of the treared group and 40 patients of the control group.

RESULTAfter treatment, the treatment in the treated group showed an effect better than that in the control group in terms of nigh-time blood pressure reducing rate (P < 0.05). The reducing blood pressure variability and total effective rate in the treated group were no significant than that in the control group. In respect of reducing symptomatic scores on dizzy, soreness and weakness of the waist and knees, disturbed and dry and bitter of mouth, ameliorating quality of life score, decreasing the levels of heart rate, total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol(HDL-C) in the treated group were showing marked improvement as compared with that in the control group (P < 0.05 or P < 0.1). The improvement in the level of Ang II , Hs-CRP and CGRP before treatment in two groups were more significant than that after treatment (P < 0.05). However There were no difference in after treatment between the treated group and the control group.

CONCLUSIONThe calming the liver and restraining the Yang formula shows favorable efficacy in lowering blood pressure on the patients with mild or moderate degree of essential hypertension. It can reduce the clincial symptoms, improve the quality of life, regulate blood lipid metabolism. Its mechanism may be related to the functional relieving inflammatory reaction and inhibition the activity of renin-angiotensin-aldosterone system (RAAS).

Adult ; Aged ; Amlodipine ; therapeutic use ; Antihypertensive Agents ; therapeutic use ; Anxiety ; chemically induced ; physiopathology ; Blood Pressure ; drug effects ; Cholesterol ; metabolism ; Cholesterol, HDL ; metabolism ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Heart Rate ; drug effects ; Humans ; Hypertension ; drug therapy ; physiopathology ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Phytotherapy ; Triglycerides ; metabolism

INTRODUCTIONThe need for the rational development of newer and adjuvant drugs to treat epilepsy has prompted this study of the potential anticonvulsant effect of amlodipine.

METHODSThe acute effect was studied in mice in single doses of 1 mg/kg, 2 mg/kg and 4 mg/kg of amlodipine and the chronic effect was studied in doses of 1 mg/kg and 4 mg/kg (administered daily for 21 days) using the maximal electroshock seizure and pentylenetetrazole-induced seizure models of epilepsy. Sodium valproate and normal saline were used as the standard and control, respectively.

RESULTSFor the acute study, in the maximal electroshock seizure model, the administration of 1 mg/kg of amlodipine resulted in the complete abolition of seizures in 33 percent of the mice, and this was increased to 67 percent with the administration of 4 mg/kg. In the pentylenetetrazole-induced seizure model, the administration of 1 mg/kg and 2 mg/kg amlodipine protected 33 percent of the animals from mortality, and 67 percent were protected with the administration of 4 mg/kg. For the chronic study, in the maximal electroshock seizure model, the administration of 1 mg/kg amlodipine resulted in the complete abolition of seizures in 40 percent of the mice and in 60 percent, with the administration of 4 mg/kg. In the pentylenetetrazole-induced seizure model, 50 percent of the mice were protected from mortality with 1 mg/kg amlodipine and 60 percent, with 4 mg/kg amlodipine.

CONCLUSIONThese findings indicate that amlodipine may be a good candidate as an add-on therapy for epilepsy.

Amlodipine ; therapeutic use ; Animals ; Anticonvulsants ; therapeutic use ; Calcium Channel Blockers ; therapeutic use ; Convulsants ; toxicity ; Disease Models, Animal ; Electroshock ; adverse effects ; Female ; Male ; Mice ; Mice, Inbred Strains ; Pentylenetetrazole ; toxicity ; Seizures ; drug therapy ; etiology ; prevention & control ; Time Factors ; Valproic Acid ; therapeutic use

OBJECTIVETo compare the effects of amlodipine, benidipine and nifedipine on myocardial hypertrophy and evaluate the underlying mechanism.

METHODSMyocardial hypertrophy model was created by transverse aortic constriction (TAC) in C57 BL/6 mice, and plasma catecholamine concentrations were measured 7 days after surgery to confirm the sympathetic activation. The 3 drugs were administered in TAC mice for 7 days and cardiac hypertrophy was evaluated according to the heart-to-body weight ratio (HW/BW). Effects of those drugs on the protein synthesis stimulated by phenylephrine in cultured neonatal cardiac myocytes were also examined.

RESULTSHW/BW and plasma concentrations of catecholamine were significantly increased in TAC mice one week after surgery in comparison with to sham-operated mice. One week after TAC, the HW/BW ratio was significantly lower in the amolodipine but not nifedipine-treated group than in the TAC group. Administration of nifedipine via minipump infusion for one week did not decrease HW/BW ratio. Treatment with amlodpine or benidipine, but not nifedipine, decreased the neonatal rat myocyte protein synthesis induced by phenylephrine stimulation.

CONCLUSIONAntihypertrophic effect of DHEs on myocardium is dependent on their potential of blocking N-type calcium channel, and the underlying mechanism involves the sympathetic inhibition.

Amlodipine ; pharmacology ; therapeutic use ; Animals ; Calcium Channel Blockers ; pharmacology ; therapeutic use ; Calcium Channels, N-Type ; drug effects ; Cardiomegaly ; drug therapy ; etiology ; Dihydropyridines ; pharmacology ; therapeutic use ; Disease Models, Animal ; Male ; Mice ; Mice, Inbred C57BL ; Nifedipine ; pharmacology ; therapeutic use