+1 Recommend
1 collections
      • Record: found
      • Abstract: found
      • Article: found

      Clinical Trials of Antiarrhythmic Therapy -An Improper Answer to a Proper Question?


      S. Karger AG

      Antiarrhythmic therapy, Clinical trials, Secondary prevention of coronary heart disease, Sudden cardiac death

      Read this article at

          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.


          Pharmacologic prevention of ventricular fibrillation (VF) and sudden cardiac death (SCD) is based on the assumption that the abnormal impulse that causes premature ventricular complexes (PVCs) may trigger VF and that antiarrhythmic drug therapy will thus inactivate the trigger. However, results available from secondary preventive trials of antiarrhythmic agents, including the Ghent-Rotterdam Aprindine (GRAP) study, have not established conclusively the value of antiarrhythmic therapy. A number of factors could explain this failure, e.g., PVCs and VF might not be causally related, thus, antiarrhythmic drugs might not prevent VF; the number of patients enrolled in investigations might have been too small to accommodate statistical proof of benefit; or the subjects might have been poorly selected. A serious design defect that could interfere with demonstrating a benefit for treatment might arise from the fact that all patients in the GRAP and similarly designed studies had to show complex ventricular arrhythmias at randomization and that antiarrhythmic treatment was usually continued regardless of its effect on the underlying arrhythmias. Given the variability of arrhythmias, it would be expected that arrhythmias would persist in only a fraction of patients randomized to placebo. However, arrhythmias also persisted, although to a lesser extent, in treated patients. If one considers that SCD risk may be reduced in the face of arrhythmia suppression but that it may be increased if the arrhythmia persists due to a toxic or proarrhythmic drug effect, any advantageous effects of successful antiarrhythmic drug therapy would be offset by the negative effects of unsuccessful arrhythmia suppression, which would distort the comparison with placebo. The design of the GRAP and similar studies precludes stratification of data to obviate this effect. To discern whether a beneficial effect exists for arrhythmia suppression, the trial design must allow for initial treatment with the subject antiarrhythmic agent to establish its antiarrhythmic effect in the patient population, after which patients should be randomized to placebo or continuation of active drug therapy. A suitable design for such a study is discussed.

          Related collections

          Author and article information

          S. Karger AG
          11 November 2008
          : 74
          : Suppl 2
          : 32-39
          Clinical Epidemiological Unit, Department of Cardiology, Erasmus University, Rotterdam, The Netherlands
          174285 Cardiology 1987;74:32–39
          © 1987 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
          Pages: 8


          Comment on this article