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

Abstract

Summary: 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).' 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.' 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? 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: Amlodipine does not have any appreciable negative inotropic effect with the relevant clinical dose? Other clinical studies have shown amlodipine to be effective when used once-daily in chronic stable angina and vasospastic angina? Comparative studies indicate that the antianginal efficacy of amlodipine is comparable to the beta blocker nadolo18 and the benzothiazepine calcium antagonist diltia~ern.~ Amlo- dipine has also been found to provide improved antianginal effects when combined to treatment with beta blockers and/or long-acting nitrates.1o. 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."We evaluated the antianginal efficacy and safety of amlodipine in a placebocontrolled multicenter randomized crossover study in patients with chronic stable angina. Key words angina pectoris, exercise tolerance, amlodiphe MethodsIn this short-term randomized double-blind crossover study (Fig. l), the effects of amlodipine (2.55, and 10 mg) oncedaily were compared with placebo in patients with chronic stable angina. After giving signed, informed consent, patients had all antianginal medications except sublingual nitroglycerin (NTG) withdrawn and entered an initial single-blind placebo period lasting up to 1 week. Patients were then randomized to 1-week double-blind therapy (amlodipine 2.5,5, or 10 mg or placebo) once daily, followed by 1-week therapy with the alternative regimen (amlodipine if placebo was given in the first double-blind period and vice versa). Patients were examined and evaluated on at least one occasion during the initial placebo period, at the end of each double-blind period, and 1 week after completion of the second double-blind period.At each visit, patients attended the clinic 1 h after a light carbohydrate breakfast taken 4 h after the dose. No tobacco or tea, coffee...

A Double-Blind, Parallel-Group Study of Amlodipine versus Long-Acting Nitrate in the Management of Elderly Patients with Stable Angina

“…There have been numerous studies supporting the use of amlodipine in treating stable angina [5, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17]. However, even with such positive data, the decisions regarding the use of calcium channel blockers in the elderly are difficult, given the relatively few elderly patients enrolled in such clinical trials.…”

“…Amlodipine is a third-generation dihydropyridine calcium channel blocker with a distinct pharmacologic profile, possessing a slow onset of action, high bioavailability and prolonged plasma elimination [4]. It has a low hepatic clearance with high (64%) oral availability [5]. …”

North of England evidence based guidelines development project: summary version of evidence based guideline for the primary care management of stable angina

“…Calcium channel blockers when used alone are more effective than placebo (I)70 86 87 88 89 90 91 92 and are all equally effective (I) 93 94 95…”

Sensitive HPLC Method With Fluorescence Detection and on-Line Wavelength Switching for Simultaneous Determination of Valsartan and Amlodipine in Human Plasma

“…[1][2][3][4] Amlodipine besylate (AML); (4 R,S)-3-ethyl-5-methyl-2-(2-aminoethoxymethyl)-4-(2-chlorophenyl)-1,4-dihydro-6-methylpyridine-3,5-dicarboxylate monobenzene sulphonate (Figure 1), is a potent long-acting calcium channel blocking agent of the dihydropyridine class. [1,[5][6][7] The combination of VAL and AML (Exforge) was recently approved by the FDA as initial or first-line therapy in patients likely to need multiple drugs to achieve their blood pressure goals. Exforge (Novartis) is a fixed-dose combination of AML and VAL, in the form of film-coated tablets.…”