Effects of amlodipine on transient myocardial ischaemia in patients with a severe coronary condition treated with a beta-blocker

The purpose of this trial was to study the additional anti-ischaemiceffects of amlodipine in coronary patients with ambulant ischaemiadespite beta-blocker therapy. Beta-blockers are the most effectivedrug therapy for reducing the frequency and duration of ambulatoryischaemic episodes. However, the therapeutic advantage of combinedcalcium antagonist-beta-blocker treatment remains questionable. Three hundred and thirteen patients with documented coronaryartery disease, a positive exercise test within 6 months beforeentry and background beta-blocker therapy, were screened. Inclusioncriteria (4 episodes of transient ST segment depression of 1.0 mm and/or 20 min of ischaemia) were demonstrated in a 48h ECG during the placebo run-in period in 84 (25%) of the patients.Eighty-nine percent of the ischaemic episodes were silent. Theeligible patients were then randomized in a 2-week, double-blind,parallel group study comparing placebo to amlodipune 10 mg dailyadded to the beta-blocker. The anti-ischaemic efficacy of thecombination therapy was assessed by 48 h ECG monitoring andexercise tests. Compared to placebo, amlodipine did not significantly reduceeither the frequency (3.7±4.3 vs 4±4.8 episodesin the amlodipune group) or the duration of ambulatory ischaemia(mean duration: 43.9±57.1 vs 39.6±65.7 min, totalduration 3.1±6.7 vs 2.8±6.1 h). Exercise-inducedST segment depression tended to decrease with amlodipine (58%vs 73% in the placebo group) and the ischaemia-free workloadcapacity was increased (+1.7 stage vs 0.7 stage in the placebogroup, P=0.08). These results suggest that 2 weeks treatment with amlodipinemay not provide any additional anti-ischaemic benefit in patientswith ambulant ischaemia resistant to a beta-blocker therapy.     

氨氯地平和培哚普利联合治疗对高血压病患者肾功能的影响

探讨氨氯地平，培哚普利单独治疗和联合治疗对高血压病患者肾功能的影响。方法 ６６例高血压病患者随机分为三组：氨氯地平组；培哚普利组；氨氯地平和培哚普利联合治疗组。疗程２４周，治疗前后观察肾功能指标变化。结果 １．氨氯地平，培哚普利及联合治疗组高血压病患者治疗后均能显著降低血压及尿蛋白排泄量「２４小时尿白蛋白：１０２±３６．４．１０４．７±４２．７和１０１．４±０．０６５，０．２４±０．６２及０．２３     

Amlodipine once a day in stable angina: Double-blind crossover comparison with placebo

Although calcium antagonists form a mainstay of therapy in patients with angina pectoris, the currently available agents have significant limitations. Nifedipine, diltiazem, and verapamil are all high-clearance agents with significant hepatic extraction and rapid clearance, leading to limited and shortlived bioavailability necessitating frequent daily administration. In contrast, amlodipine, a dihydropyridine calcium antagonist, has a long half-life of 35–50 h (compared with 3 to 4 h elimination half-life of diltiazem, verapamil, and nifedipine).¹ After oral doses, the relative bioavailability of amlodipine is high (64%) and absorption is smooth, with peak plasma levels being achieved 6–12 h postdose.¹ Bioavailability is not affected by the consumption of food.² In common with other dihydropyridine calcium antagonists, amlodipine is eliminated mainly by metabolism.³ None of the metabolites of amlodipine has significant calcium antagonist effects in humans.³ In contrast to verapamil or diltiazem, amlodipine has no effect on sinus or atrioventricular node⁴ and little or no effect on the resting heart rate.⁵ Amlodipine does not have any appreciable negative inotropic effect with the relevant clinical dose.⁶ Other clinical studies have shown amlodipine to be effective when used once-daily in chronic stable angina and vasospastic angina.⁷ Comparative studies indicate that the antianginal efficacy of amlodipine is comparable to the beta blocker nadolol⁸ and the benzothiazepine calcium antagonist diltiazem.⁹ Amlodipine has also been found to provide improved antianginal effects when combined to treatment with beta blockers and/or long-acting nitrates.^{10, 11} Treatment with amlodipine either as monotherapy or combined with other antianginal therapy for up to 26 weeks shows that efficacy is maintained, with no evidence of tolerance.¹¹ We evaluated the antianginal efficacy and safety of amlodipine in a placebo-controlled multicenter randomized crossover study in patients with chronic stable angina.     

Effects of Amlodipine and Isosorbide Dinitrate on Exercise-Induced and Ambulatory Ischemia in Patients with Chronic Stable Angina Pectoris

This study was designed to compare once-daily administration of 5–10 mg amlodipine with two daily doses of 40 mg sustained-release isosorbide dinitrate in 59 patients with stable angina using a randomized, double-blind, crossover study design. Anginal episodes, nitroglycerin consumption, and possible adverse events were recorded in a diary. A maximal symptom-limited bicycle exercise test and 48-hour ambulatory ECG monitoring were performed at baseline and at the end of each 5-week period of therapy. Exercise time, time to angina, time to ST depression, and maximal ST depression were measured during exercise. During ambulatory monitoring, the number of ischemic episodes and the duration per hour of ST depression were assessed. Amlodipine significantly reduced anginal episodes (P < 0.001) when compared with isosorbide dinitrate. Furthermore, amlodipine prolonged time to ST depression (P < 0.001) and time to angina (P < 0.05) when compared with isosorbide dinitrate. The number and duration of ischemic episodes during ambulatory monitoring were significantly reduced with amlodipine when compared with baseline values (P < 0.05), whereas no differences were found between isosorbide dinitrate and baseline. Adverse events were reported more frequently with isosorbide dinitrate than with amlodipine (P < 0.02). Amlodipine appears to be more effective and tolerable than sustained-release isosorbide dinitrate as monotherapy for chronic stable angina. This revised version was published online in July 2006 with corrections to the Cover Date.     

Acute Hemodynamic Effects of Amlodipine 15 Days After a Myocardial Infarction in Normotensive Patients Treated with Atenolol

The acute hemodynamic effects of 20 mg iv amlodipine were evaluated in a placebo-controlled study in 16 normotensive patients 15 ± 1 days after an acute myocardial infarction by covariance analysis. Atenolol was given orally for at least 1 week before the study to maintain the heart rate between 50 and 60 beats/min. All patients were given two doses of 10 mg of amlodipine, or 10 ml of a placebo twice, in iv infusion lasting 2 minutes each. Hemodynamic data were collected during the control period and 15 minutes after each of the two amlodipine or placebo infusions. At the time of the last measurements, 15 minutes after the second amlodipine or placebo infusion, the plasma amlodipine level was 31 ± 16 g/l and the plasma atenolol level was 773 ± 564 /l in the amlodipine group versus 795 ± 916 g/l in the placebo group. There were no chronotropic, dromotropic, or inotropic effects. The main hemodynamic effect was a fall in systemic vascular resistance (1548 ± 591 dynes.sec.cm^-5to 1176 ± 526 dynes.sec.cm^-5, p = 0.045) with decreases in aortic pressure and in the left ventricular stroke work index. The left ventricular ejection fraction was 51 ± 12% in the placebo group and 56 ± 15% in the amlodipine group (ns) during the control period, and did not change after infusion of placebo or amlodipine. Left ventricular compliance seemed to be enhanced by amlodipine, because the end-diastolic left ventricular volume index rose from 82 ± 11 ml/m² to 87 ± 11 ml/m² (p = 0.026) 15 minutes after the beginning of the second infusion of 10 mg of amlodipine, without any change in end-diastolic left ventricular pressure. Intravenous infusion of 20 mg of amlodipine is well tolerated 15 days after acute myocardial infarction in normotensive patients without deeply depressed left ventricular systolic function and chronically treated with atenolol. The main hemodynamic effects observed are potentially useful for such patients.     

苯磺酸氨氯地平和缬沙坦治疗清晨高血压的疗效观察

目的：比较苯磺酸氨氯地平和缬沙坦控制清晨高血压的效果差异。方法：从社区高血压健康自我管理小组患者中选择原发性高血压患者200例,筛选出清晨高血压患者88例,入选患者停用抗高血压药物14 d,将入选患者分为2组,其中服用苯磺酸氨氯地平41例患者为观察组,服用缬沙坦47例患者为对照组,观察4周清晨血压（家庭自测血压）,比较2组患者清晨血压控制情况。结果：苯磺酸氨氯地平和缬沙坦2种药物均能明显降低收缩压（P〈0.01）,但观察组清晨血压控制更好,收缩压低于对照组（P〈0.01）。结论：苯磺酸氨氯地平和缬沙坦均为比较安全和有效的长效抗高血压药物,但在清晨高血压的控制方面,苯磺酸氨氯地平控制收缩压明显优于缬沙坦,而对舒张压无明显影响。     

Comparison of the Effects of Amlodipine and Losartan on Blood Pressure and Diurnal Variation in Hypertensive Stroke Patients: A Prospective,Randomized, Double-Blind,Comparative Parallel Study

Background

Lowering blood pressure (BP) and reducing diurnal variation are important for the prevention of stroke in patients with hypertension.

Objective

This study was conducted to compare the BP-lowering and diurnal BP variation effects of amlodipine and losartan on acute stroke patients.

Methods

Seventy-seven hypertensive patients with acute stroke were enrolled in this randomized, double-blind, single-center clinical trial. They were randomly assigned to receive either amlodipine or losartan daily. To evaluate whether amlodipine was noninferior to losartan, ambulatory BP monitoring was performed before the drugs were first administered and at the end of week 8. BP variables analyzed included the mean awake, sleep, morning, evening, and prewake BP values; the nocturnal dipping status; and the morning surge.

Results

Thirty-nine patients in the amlodipine group and 38 patients in the losartan group completed the follow-up. In the baseline characteristics, mean age was 63.6 years, and 68.8% were male. In the intention-to-treat analysis, the mean (SD) systolic BP decreased 14.82 (11.71) mm Hg in the amlodipine group and 13.11 (12.69) mm Hg in the losartan group, and amlodipine proved noninferior to losartan (mean difference, 1.71 mm Hg [95% CI, –3.83 to 7.26]). However, in the per-protocol analysis, noninferiority was not proven (BP reduction, 16.06 [11.33] vs 17.17 [11.85] mm Hg; mean difference, –1.11 mm Hg [95% CI, –6.88 to 4.65]). Amlodipine had a greater tendency than losartan to produce a blunt morning surge.

Conclusions

The noninferiority of amlodipine was not confirmed by the per-protocol analysis. However, amlodipine showed a favorable effect on the morning surge. ClinicalTrials.gov identifier: NCT01830517.     

MULTICENTER PARALLEL STUDY OF AMLODIPINE VERSUS NITRENDIPINE IN THE TREATMENT OF ESSENTIAL HYPERTENSION

ＭＵＬＴＩＣＥＮＴＥＲＰＡＲＡＬＬＥＬＳＴＵＤＹＯＦＡＭＬＯＤＩＰＩＮＥＶＥＲＳＵＳＮＩＴＲＥＮＤＩＰＩＮＥＩＮＴＨＥＴＲＥＡＴＭＥＮＴＯＦＥＳＳＥＮＴＩＡＬＨＹＰＥＲＴＥＮＳＩＯＮＷａｎｇＸｉａｎｙａｎ（王宪衍）；ＧｏｎｇＬａｎｓｈｅｎｇ（龚兰生）...     

EFFECT OF CHRONIC TREATMENT WITH AMLODIPINE IN NON-INSULIN-DEPENDENT DIABETIC RATS

We have investigated the effects of amlodipine on streptozotocin- (STZ) induced neonatal non-insulin-dependent diabetes mellitus (NIDDM) rats. NIDDM was induced by intraperitoneal injection of STZ (70 mg kg⁻¹) to 5-day-old rat pups. The animals were weaned at 30 days and maintained with food and waterad libitumfor 3 months. Amlodipine (5 mg kg⁻¹p.o.) was administered for 6 weeks after the animals were confirmed diabetic (3 months after the STZ injection). A group of control animals were also maintained and this group received citrate buffer 5 days after birth. Fasting- and fed-glucose levels in NIDDM rats were significantly higher than control rats. Treatment with amlodipine reduced the elevated fasting- and fed-glucose levels significantly. Results of the oral glucose tolerance test (OGTT) revealed that glucose tolerance is impaired in the NIDDM rats. There was a marked increase in glucose levels after oral administration of glucose in the control NIDDM rats. Increased glucose levels were found to be associated with increased insulin levels. Treatment with amlodipine in the NIDDM rats caused a decrease in insulin release, however, glucose levels were found to be lowered significantly indicating that amlodipine causes an increase in insulin sensitivity. In conclusion, our data indicated that amlodipine increases insulin sensitivity in neonatal-STZ NIDDM rats.