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      Potential Cardioprotective Effect of Mibefradil in the Long-Term Treatment of Hypertension


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          During the last 2 decades, remarkable progress has been made in the treatment of hypertension with the discovery of new drugs lowering blood pressure by various mechanisms, e.g. calcium channel blockers, angiotensin-converting enzyme inhibitors and angiotensin II antagonists. These antihypertensive agents are now widely used as first-line therapy although there is still no definite proof that they have a cardioprotective effect and reduce the mortality rate in patients with coronary heart disease. Mibefradil is a new calcium antagonist with a novel mechanism of action since it is the only drug available so far able to block T channels. This compound might be particularly effective in preventing cardiac morbidity and mortality. It reduces heart rate when lowering blood pressure, has no negative inotropic effect, allows regression of cardiac hypertrophy and is effective in the treatment of angina. Mibefradil produces a sustained blood pressure reduction with a close to optimal trough:peak ratio. A major advantage of this novel compound is its excellent tolerability over the dose range recommended (50–100 mg/day). In particular, leg edema is seen clearly less often during mibefradil treatment than during therapy with dihydropyridines. Mibefradil has therefore an attractive profile in terms of both efficacy and safety and represents a promising first-line option to treat hypertensive patients.

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          Most cited references 9

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          Single-drug therapy for hypertension in men. A comparison of six antihypertensive agents with placebo. The Department of Veterans Affairs Cooperative Study Group on Antihypertensive Agents.

          Characteristics such as age and race are often cited as determinants of the response of blood pressure to specific antihypertensive agents, but this clinically important issue has not been examined in sufficiently large trials, involving all standard treatments, to determine the effect of such factors. In a randomized, double-blind study at 15 clinics, we assigned 1292 men with diastolic blood pressures of 95 to 109 mm Hg, after a placebo washout period, to receive placebo or one of six drugs: hydrochlorothiazide (12.5 to 50 mg per day), atenolol (25 to 100 mg per day), captopril (25 to 100 mg per day), clonidine (0.2 to 0.6 mg per day), a sustained-release preparation of diltiazem (120 to 360 mg per day), or prazosin (4 to 20 mg per day). The drug doses were titrated to a goal of less than 90 mm Hg for maximal diastolic pressure, and the patients continued to receive therapy for at least one year. The mean (+/- SD) age of the randomized patients was 59 +/- 10 years, and 48 percent were black. The average blood pressure at base line was 152 +/- 14/99 +/- 3 mm Hg. Diltiazem therapy had the highest rate of success: 59 percent of the treated patients had reached the blood-pressure goal at the end of the titration phase and had a diastolic blood pressure of less than 95 mm Hg at one year. Atenolol was successful by this definition in 51 percent of the patients, clonidine in 50 percent, hydrochlorothiazide in 46 percent, captopril in 42 percent, and prazosin in 42 percent; all these agents were superior to placebo (success rate, 25 percent). Diltiazem ranked first for younger blacks ( or = 60 years), among whom the success rate was 64 percent, captopril for younger whites (success rate, 55 percent), and atenolol for older whites (68 percent). Drug intolerance was more frequent with clonidine (14 percent) and prazosin (12 percent) than with the other drugs. Among men, race and age have an important effect on the response to single-drug therapy for hypertension. In addition to cost and quality of life, these factors should be considered in the initial choice of a drug.
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                Author and article information

                S. Karger AG
                February 1998
                03 March 1998
                : 89
                : Suppl 1
                : 16-22
                Division of Hypertension, CHUV, Lausanne, Switzerland
                47275 Cardiology 1998;89(suppl 1):16–22
                © 1998 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                Page count
                Figures: 5, Tables: 1, References: 34, Pages: 7


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