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      A Comparison of the Effects of Mibefradil and Atenolol on Regression of Left Ventricular Hypertrophy in Hypertensive Patients

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          Objective: This study was designed to compare the effect of mibefradil, a selective T-type calcium channel antagonist, with the β-blocker atenolol on regression of left ventricular (LV) hypertrophy in hypertensive patients. Methods: In this multicenter, double-blind, active-controlled, randomized, parallel-group comparison, 66 patients with mild-to-moderate hypertension (sitting diastolic blood pressure, SDBP, 95–114 mm Hg) and LV mass index >102 g/m<sup>2</sup> for males and >88 g/m<sup>2</sup> for females were randomized to an initial treatment with 50 mg of either mibefradil or atenolol for 4 weeks. Doses were increased to 100 mg/day if blood pressure was not normalized to ≤90 mm Hg, and, if needed, 25 mg of hydrochlorothiazide was added. Treatment continued for a total of 24 weeks. LV hypertrophy was assessed by echocardiography, and trough SDBP and adverse events were recorded. Results: Treatment with mibefradil or atenolol resulted in decreases from baseline in LV mass index of 11.1% (p < 0.001) and 9.1% (p < 0.001), respectively. The treatment difference (mibefradil vs. atenolol) was not statistically significant. Reductions in SDBP with mibefradil and atenolol were 14.3 and 10.7 mm Hg, respectively, again not statistically significant. Both drugs were well tolerated; however, overall there were more potentially drug-related adverse events reported with atenolol (48.5%) than with mibefradil (24.2%). Conclusions: The reductions in LV hypertrophy and blood pressure achieved with mibefradil were larger but statistically equivalent to those with atenolol, but a lower overall incidence of treatment-related adverse events was seen in the mibefradil-treated patients.

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          Reversal of left ventricular hypertrophy in essential hypertension. A meta-analysis of randomized double-blind studies.

          To determine the ability of various antihypertensive agents to reduce left ventricular hypertrophy, a strong, blood pressure-independent cardiovascular risk factor, in persons with essential hypertension. MEDLINE, DIMDI, RINGDOC, ADES, EMBASE, and review articles through July 1995 (English-language and full articles only). Meta-analysis of all published articles including only double-blind, randomized, controlled clinical studies with parallel-group design. Intensive literature search and data extraction according to a prefixed scheme performed independently by 2 investigators. Reduction of left ventricular mass index after antihypertensive therapy with placebos, diuretics, beta-blockers, calcium channel blockers, or angiotensin-converting enzyme (ACE) inhibitors was the principal parameter. Of 471 identified references describing the effects of antihypertensive drugs on left ventricular hypertrophy, only 39 clinical trials fulfilled the inclusion criteria of our study. We found that the decrease in left ventricular mass index was more marked the greater was the decline in blood pressure (systolic r=0.46, P<.001; diastolic r=0.21, P=.08) and the longer was the duration of therapy (r=0.38, P<.01). After adjustment for different durations of treatment (mean duration of treatment, 25 weeks), left ventricular mass decreased 13% with ACE inhibitors, 9% with calcium channel blockers, 6% with beta-blockers, and 7% with diuretics. There was a significant difference between drug classes (P<.01): ACE inhibitors reduced left ventricular mass more than beta-blockers (significant, P<.05) and diuretics (tendency, P=.08). Similar differences between drug classes were found with regard to effect on left ventricular wall thickness (P<.05). The database of articles published through July 1995 is small and incomplete, and most of the articles are of poor scientific quality. In this first meta-analysis including only double-blind, randomized, controlled clinical studies, decline in blood pressure, duration of drug treatment, and drug class determined the reductions in left ventricular mass index. The ACE inhibitors seemed to be more potent than beta-blockers and diuretics in the reduction of left ventricular mass index; calcium channel blockers were somewhat in the intermediate range. The ACE inhibitors and, to a lesser extent, calcium channel blockers emerged as first-line candidates to reduce the risk associated with left ventricular hypertrophy.
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            Dose-Response Characteristics of Mibefradil, a Novel Calcium Antagonist, in the Treatment of Essential Hypertension

             S Oparil (1997)

              Author and article information

              S. Karger AG
              May 1998
              29 October 2008
              : 89
              : 4
              : 263-270
              a Stockholm Heart Center, Stockholm, Sweden; b Institute of Clinical Experimental Medicine, Prague, Czech Republic; c Hôpital Lapeyronie, Montpellier, France; d St. Emeric Teaching Hospital, Budapest, Hungary; e University of Aberdeen Medical School, Aberdeen, and f Hammersmith Hospital, London, UK; g F. Hoffmann-La Roche AG, Basel, Switzerland
              6798 Cardiology 1998;89:263–270
              © 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: 1, Tables: 5, References: 31, Pages: 8
              Clinical Pharmacology


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