Hemodynamic and Cardiac Effects of the Selective T-Type and L-Type Calcium Channel Blocking Agent Mibefradil in Patients With Varying Degrees of Left Ventricular Systolic Dysfunction11This work was supported in part by a grant from Hoffmann-La Roche, Basel, Switzerland. It was presented in part at the 67th Scientific Sessions of the American Heart Association, Dallas, Texas, November 1994.

Rousseau, Michel F.; Hayashida, Wataru; Eyll, Christian van; Hess, Otto M.; Benedict, Claude R.; Chapelle, F.; Kobrin, Isaac; Pouleur, H.

doi:10.1016/s0735-1097(96)00261-6

Cited by 40 publications

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“…Pro‐ischaemic effects have been attributed to some calcium antagonists and are most likely related to their reflex tachycardia, sympathetic activation, or the coronary steal phenomenon 31 . Mibefradil is not associated with these effects and lacks any relevant negative inotropic effect 7‐9,32 . Because of these properties, the use of this agent in patients with congestive heart failure (NYHA classes II‐IV) is under investigation in a large mortality trial 33…”

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confidence: 99%

“…In contrast to all other available calcium antagonists which block only the L‐type calcium channels at therapeutic concentrations, mibefradil exerts its pharmacological effects by selectively blocking T‐type voltage‐dependent calcium channels, in addition to L‐type calcium channels 2‐4 . Although the clinical implications of this new mechanism of action have not been fully elucidated, mibefradil was found to have a unique pharmacological profile, characterised by peripheral and coronary vasodilatation; a potentially beneficial decrease in heart rate; and a lack of negative inotropic effect at recommended doses 5‐9 . Clinical pharmacokinetic studies have demonstrated that mibefradil has high bioavailability (approximately 80% at steady state) and a relatively long half‐life (17‐25 hours), with low inter‐ and intra‐patient variability in plasma concentrations 10 .…”

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The Efficacy and Safety of Mibefradil in Subgroups of Patients With Chronic Stable Angina Pectoris

Charlon

Kobrin

1998

Int J Clinical Practice

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SUMMARYThe pool of controlled clinical studies on mibefradil, a new selective T‐type calcium channel blocker, for the treatment of chronic stable angina pectoris was analysed to determine the effects in subgroups of patients defined by age, gender, body weight and common co‐existing conditions. Total exercise tolerance test duration increased similarly in all subgroups, both at 50 mg (range 8.9‐17.3%; n=383) and 100 mg mibefradil (range 23.6‐30.8%; n=235). The increases in time to onset of angina and 1 mm ST‐segment depression were similarly comparable. Safety and tolerability was similar to placebo for subgroups at 50 mg, but the incidence of adverse events was slightly higher in females, older, and lower weight patients at the 100 mg dose, particularly in reported leg oedema (7.9% in females vs 1.0% in males and 5.1% in older vs 0% in younger patients). Mibefradil proved a safe, well tolerated, and effective antianginal agent that can be used regardless of demographic factors or of frequent coexisting clinical conditions.

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The Efficacy and Safety of Mibefradil in Subgroups of Patients With Chronic Stable Angina Pectoris

Charlon

Kobrin

1998

Int J Clinical Practice

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Myocardial Infarction Agents

Altschuld

2003

Burger's Medicinal Chemistry and Drug Discovery

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A myocardial infarction begins with the occlusion of a coronary artery, usually resulting from the rupture of an atherosclerotic plaque. Pharmacologic treatment begins with conventional pain relief and under appropriate circumstances thrombolytic agents are administered. Anticoagulants are used in conjunction with thrombolytic agents to assist thrombolysis and prevent reocclusion of the affected vessel. Lethal arrhythmias such as ventricular fibrillation are a major cause of death following myocardial infarction. β‐Adrenoceptor antagonists are used to reduce the incidence of this sudden cardiac death. Angiotensin converting enzyme inhibitors are used to reduce post‐infarction ventricular remodeling, which is a leading cause of congestive heart failure. Current therapy has significantly reduced in hospital mortality but acute myocardial infarction remains the leading cause of death in the United States. Congestive heart failure secondary to myocardial infarction is becoming an epidemic. Additional therapeutic agents and/or strategies are needed to reduce death and disability following myocardial infarction.

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Antihypertensive effects of mibefradil: A double‐blind comparison with diltiazem CD

Massie

Chrysant

Jain

et al. 1997

Clinical Cardiology

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SummaryBrrckgmund und hypothesis: Mibefradil is the first compound of a new class of calcium antagonists with a unique chemical structure and mechanism of action. This trial compared mibefradil with diltiazem CD, a widely prescribed calcium antagonist for the treatment of hypertension.Methods: In all, 201 patients with uncomplicated, mild-tomoderate essential hypertension with a baseline sitting diastolic blood pressure (SDBP) of 295 and 5 114 mmHg were evenly randomized to receive either mibefradil (1 00 mg) or diltiazem CD (360 mg) daily for 12 weeks. To determine whether antihypertensive effects persisted after 12 weeks, patients then entered a 4-week withdrawal period during which they remained on active treatment or were switched to placebo.Results: Efficacy variables were the changes from baseline in SDBP to the end of the treatment period (Week 12) and during the randomized withdrawal period (Week 16). At Week 12, the reduction from baseline in SDBP at trough was significantly greater (p<0.001) in the mibefradilgroup (-14.0+ 7.8 mmHg) than in the diltiazem CD group (-9.5 + 7.5 mmHg).Significantly more patients (72%) on mibefradil achieved SDBP normalization by Week 12 than did patients on diltiazem ( 5 1%) (p<0.01). Patients maintained on inibefradil or diltiazem CD during the withdrawal period had a significantly larger reduction in trough SDBP at Week 16 than those switched to placebo. The incidence of side effects was similar in both treatment groups.Conclusions: Once-daily mibefradil was equally well tolerated as diltiazem CD, but was more effective in lowering blood pressure at the doses studied than the extended-release formulation of diltiazem.

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Abstract: Intravenous mibefradil was well tolerated and produced an overall favorable cardiovascular response. However, high plasma concentrations might produce myocardial depression in patients with heart failure, and caution should be exerted in this setting.

Cited by 40 publications

References 16 publications

The Efficacy and Safety of Mibefradil in Subgroups of Patients With Chronic Stable Angina Pectoris

The Efficacy and Safety of Mibefradil in Subgroups of Patients With Chronic Stable Angina Pectoris

Myocardial Infarction Agents

Antihypertensive effects of mibefradil: A double‐blind comparison with diltiazem CD

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