Cardiac Arrhythmias: New Therapeutic Drugs and Devices: Proceedings of the Symposium on New Drugs and Devices, held at Philadelphia, PA October 4 and 5, 1984

358 Pages·1985·7.86 MB·English

by  E. Neil Moore D.V.M.

CARDIAC ARRHYTHMIAS:
New Therapeutic Drugs
and Devices
DEVELOPMENTS IN CARDIOVASCULAR MEDICINE
Lancee, C.T., ed.: Echocardiology, 1979. ISBN 90-247-2209-8.
Baan, J., Arntzenius, A.C., Yellin, E.L., eds.: Cardiac dynamics. 1980. ISBN 90-247-2212-8.
Thalen, H.J.T., Meere, C.C., eds.: Fundamentals of cardiac pacing. 1970. ISBN 90-247-2245-4.
Kulbertus, H.E., Wellens, H.J.J., eds.: Sudden death. 1980. ISBN 9O-247-2290-X.
Dreifus, L.S., Brest, A.N., eds.: Clinical applications of cardiovascular drugs. 1980. ISBN
90-247-2295-0.
Spencer, M.P., Reid, J.M., eds.: Cerebrovascular evaluation with Doppler ultrasound. 1981. ISBN
90-247-2348-1.
Zipes, D.P., Bailey, J.C. Elharrar, V., eds.: The slow inward current and cardiac arrhythmias. 1980.
ISBN 90-247-2380-9.
Kesteloot, H., Joossens, J.V., eds.: Epidemiology of arterial blood pressure. 1980. ISBN 90-247-2386-8.
Wackers, F.J.T., ed.: Thallium-20l and technetium-99m-pyrophosphate myocardial imaging in the
coronary care unit. 1980. ISBN 90-247-2396-5.
Maseri, A., Marchesi, C., Chierchia, S., Trivella, M.G., eds.: Coronary care units. 1981. ISBN
90-247-2456-2.
Morganroth, J. Moore, E.N., Dreifus, L.S., Michelson, E.L., eds.: The evaluation of new anti-
arrhythmic drugs. 1981. ISBN 90-247-2474-0.
Alboni, P.: Intraventricular conduction disturbances. 1981. ISBN 9O-247-2483-X.
Rijsterborgh, H., ed.: Echocardiology. 1981. ISBN 90-247-2491-0.
Wagner, G.S., ed.: Myocardial infarction. Measurement and intervention. 1982. ISBN 90-247-2513-5.
Meltzer, R.S., Roelandt, J., eds.: Contrast echocardiography. 1982. ISBN 90-247-2531-3.
Amery, A., Fagard, R., Lijnen, R., Staessen, J., eds.: Hypertensive cardiovascular disease;
pathophysiology and treatment. 1982. ISBN 90-247-2534-8.
Bouman, L.N., Jongsma, H.J., eds.: Cardiac rate and rhythm. 1982. ISBN 90-247-2626-3.
Morganroth, J., Moore, E.N., eds.: The evaluation of beta blocker and calcium antagonist drugs. 1982.
ISBN 90-247-2642-5.
Rosenbaum, M.B., ed.: Frontiers of cardiac electrophysiology. 1982. ISBN 90-247-2663-8.
Roelandt, J., Hugenholtz, P.G., eds.: Long-term ambulatory electrocardiography. 1982. ISBN
90-247-2664-8.
Adgey, A.J., ed.: Acute phase of ischemic heart disease and myocardial infarction. 1982. ISBN
90-247-2675-1.
Hanrath, P., Bleifeld, W., Souquet, eds.: Cardiovascular diagnosis by ultrasound. Transesophageal,
computerized, contrast, Doppler echocardiography. 1982. ISBN 90-247-2692-1.
Roelandt, J., ed.: The practice of M-mode and two-dimensional echocardiography. 1983. ISBN
90-247-2745-6.
Meyer, J., Schweizer, P., Erbel, R., eds.: Advances in noninvasive cardiology. 1983. ISBN
0-89838-576-8.
Morganroth, Joel, Moore, E.N., eds.: Sudden cardiac death and congestive heart failure: Diagnosis and
treatment. 1983. ISBN 0-89838-580-6.
Perry, H.M., ed.: Lifelong management of hypertension. ISBN 0-89838-582-2.
Jaffe, E.A., ed.: Biology of endothelial cells. ISBN 0-89838-587-3.
Surawicz, B., Reddy, C.P., Prystowsky, E.N., eds.: Tachycardias. 1984. ISBN 0-89838-588-1.
Spencer, M.P., ed.: Cardiac Doppler diagnosis. ISBN 0-89838-591-1.
Villareal, H.V., Sambhi, M.P., eds.: Topics in pathophysiology of hypertension. ISBN 0-89838-595-4.
Messerli, F.H., ed.: Cardiovascular disease in the elderly. 1984. ISBN 0-89838-596-2.
Simoons, M.L., Reiber, J.H.C., eds.: Nuclear imaging in clinical cardiology. ISBN 0-89838-599-7.
Ter Keurs, H.E.D.J., Schipperheym, J.J., eds.: Cardiac left ventricular hypertrophy. ISBN
0-89838-612-8.
Sperelakis, N., ed.: Physiology and pathophysiology of the heart. ISBN 0-89838-615-2.
Messerli, F.H., ed.: Kidney in essential hypertension. 1983. ISBN 0-89838-616-0.
Sambhi, M.P., ed.: Fundamental fault in hypertension. ISBN 0-89838-638-1.
Marchesi, D., ed.: Ambulatory monitoring: Cardiovascular system and allied applications. ISBN
0-89838-642-X.
Kupper, W., Macalpin, R.N., Bleifeld, W., eds.: Coronary tone in ischemic heart disease. ISBN
0-89838-646-2.
Sperelakis, N., Caulfield, J.B., eds.: Calcium antagonists: Mechanisms of action on cardiac muscle and
vascular smooth muscle. ISBN 0-89838-655-1.
Godfraind, T., Herman, A.S., Wellens, D., eds.: Entry blockers in cardiovascular and cerebral
dysfunctions. ISBN 0-89838-658-6.
Morganroth, J., Moore, E.N., eds.: Interventions in the acute phase of myocardial infarction. ISBN
0-89838-659-4.
Abel, F.L., Newman, W.H., eds.: Functional aspects of the normal, hypertrophied, and failing heart.
ISBN 0-89838-665-9.
Sideman, S., and Beyar, R., eds.: Simulation and imaging of the cardiac system. ISBN 0-89838-687-X.
van de Wall, E., Lie, K.I., eds.: Recent views on hypertrophic cardiomyopathy. ISBN 0-89838-694-2.
Beamish, R.E., Singal, P.K., Dhalla, N.S., eds.: Stress and heart disease. ISBN 089838-709-4.
Beamish, R.E., Panagia, V., Dhalla, N.S., eds.: Pathogenesis of stress-induced heart disease. ISBN
0-89838-710-8.
CARDIAC ARRHYTHMIAS:
New Therapeutic Drugs
and Devices
Proceedings of the Symposium on
New Drugs and Devices, held at Philadelphia, P A
October 4 and 5, 1984
edited by
Joel Morganroth
Likoff Cardiovascular Institute
of Hahnemann Medical College and Hospital
and
E. Neil Moore
School of Veterinary Medicine
University of Pennsylvania
Martinus Nijhoff Publishing
a member of the Kluwer Academic Publishers Group
Boston/DordrechtiLancaster
Distributors for North America:
Kluwer Academic Publishers
190 Old Derby Street
Hingham, MA 02043
Distributors Outside North America:
Kluwer Academic Publishers Group
Distribution Centre
P.O. Box 322
3300 AH Dordrecht
THE NETHERLANDS
Library of Congress Cataloging in Publication Data
Symposium on New Drugs and Devices (5th: 1984:
Philadelphia, Pa.)
Cardiac arrhythmias.
(Developments in cardiovascular medicine)
I. Arrhythmia-Chemotherapy-Evaluation-Congresses.
2. Myocardial depressants-Congresses. 3. Arrhythmia
Treatment - Instruments-Congresses. 4. Cardiovascular
instruments, Implanted-Congresses. I. Morganroth, Joel.
II. Moore, E. Neil. III. Title. IV. Series.
[DNLM: I. Anti-Arrhythmia Agents-standards-congresses.
2. Anti-Arrhythmia Agents-therapeutic use-congresses.
3. Arrhythmia-therapy-congresses. 4. Pacemaker
Arti ficial-therapeutic use-congresses.
WI DE997VME / QV 150 S98972 1984c)
RC685.A65S965 1984 616.1 '28061 85-4846
ISBN-13: 978-1-4612-9626-3 e-ISBN-13: 978-1-4613-2595-6
DOl: 10.1007/978-1-4613-2595-6
Copyright © 1985 by Martinus Nijhoff Publishing, Boston
Softcover reprint of the hardcover 1st edition 1985
All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or
transmitted in any form or by any means, mechanical, photocopying, recording, or otherwise,
without written permission of the publisher, Martinus Nijhoff Publishing, 190 Old Derby Street,
Hingham, Massachusetts 02043.
OONI'ENTS
FAaJLTY viii
PREFACE x
I
IW3IC CONSIDERATIOOS 1
1
What animal rrodels are useful in selecting new
antiarrhythmic drugs? 3
E. NEIL MX>RE and JOSEPH F. SPEAR
2
How to test for antiarrhythmic drugs 12
BRIAN F. HOFFMAN
3
Initial evaluation of new antiarrhythmic agents in
man: nonnal voltmteers or patients? 22
RAYIDND L. VO)8LEY and JOHN A. OATES
4
Is there a rational basis for the rrodified
classification of antiarrhythmic drugs? 36
OONAID C. HARRISOO
Panel Discussion: Basic oonsiderations 41
II
STA'IUS OF SPOCIFIC ANl'IARRHYTHMIC AGENTS 49
5
Procainamide, Quinidine, Disopyramide, Cibenzoline,
Pirmerol - efficacy in the treatrrent of ventricular
arrhythmias: current status and oontroversies 51
CRAIG M. PRATT
6
~letine, 'Ibcainide and EthIrozine: newer class I
antiarrhythmic agents 68
ALIAN M. GREENSPAN
7
Class IC antiarrhythmic agents: status - 1984 98
JOEL IDRGANIDI'H
8
Role of beta-blocking agents in the treatrrent of
ventricular arrhythmias 132
JOEL MJRGANIDI'H
vi
9
Status of class III antiarrhythmic drugs: Amiodarone,
Bretylium and Sotalol 143
LEDNARD N. HORCMITZ
Panel Discussion: Status of specific antiarrhytlmd.c agents 167
III
SPECIAL CDNSlIERATIONS AND FDA STANDARlE 179
10
Sane tb:>ughts on efficacy trials of antiarrhythmic
agents: pitfalls of mimicking clinical practice 181
GOROON PLEDGER
11
Use of a aatpUter in the new drug evaluation process 184
STE.WARI' J. EHRREICH
12
SUdden cardiac death - failure or effect of
antiarrhythmic drug therapy? 191
IDNAID W. F. CAMPBELL
13
Sudden death as an end-point for the clinical
evaluation of antiarrhythmic drugs 201
JAY. N. COON and ~ REx:IDR
14
Holter/exercise and e1ect:rop~ologic nethods for
evaluating drug therapy for rralignant ventricular
arrhythmias: do we need both node1s? 211
J. 'l.'fK:MAS BIGGER, JR.
Panel Discussion: Special considerations and FDA standards 223
IV
NEW ANI'IARRHYTHMIC DEVICES 235
15
DVI vs DOD pacemakers - proarrhythmic or antiarrhytmri.c? 237
S. R. SPmMAN
16
Pacing for ventricular tachycardia 247
JOHN D. FISHER
17
Tennination of ventricular tachycardia by transvenous
cardioversion 255
ERIC N. PRY~KY, WILLIl\M M. MILES, JAMES J. HEX;ER,
and OOUGIAS P. ZIPES
vii
18
The automatic irrplantable cardioverter/defibrillator 262
RX;ER A. WINKLE, DEBRA S. EOn', R. HARI:M.IN MEAD,
VIN::ENl' GAUDIANI, EDWARD B. STINS(lIJ, and PAUIA SCHMIJJI'
19
New antiarrhythmia devices - FDA's requirerrents for
effectiveness 273
GLENN A. RAIM)ELLER
Panel Discussion: New antiarrhythmic devices 279
V
ElJAIDATION OF ATRIAL ARRHYTHMIAS 291
20
Study designs to evaluate atrial arrhythmias are easy 293
OOBERI' TEMPLE
21
Role of th:! autonanic nervous system in the generation
of supraventricular tachyarrhytllrnias: clues to drug
selection 307
AUGUST M. WATANABE
22
Approaches to drug selection and serial drug testing 315
JOHN C. SCMBERG and VIlMA 'roRRES
Panel Discussion: Evaluation of atrial arrhythmias 335
PARI'ICIPANI'S 345
1984 Fifth Annual Symposium on New Drugs and Devices
FACULTY
J. Thomas Bigger, Jr., M.D.
Professor of Medicine and Pharmacology
Columbia University
Ronald W. F. Campbell, M.D.
Senior Lecturer in Cardiology and
Honorary Consultant Cardiologist
Freeman Hospital, England
Jay N. Cohn, M.D.
Professor of Medicine
Head, Cardiovascular Division
University of Minnesota Medical School
Stewart J. Ehrreich, Ph.D.
Deputy Director, Cardio-Renal Division
Food and Drug Administration
John D. Fisher, M.D.
Associate Professor of Medicine
Albert Einstein College of Medicine
Allan M. Greenspan, M.D.
Associate Professor of Medicine
Hahnemann University
Donald C. Harrison, M.D.
William G. Irwin Professor of Cardiology
Stanford University
Brian F. Hoffman, M.D.
David Hosack Professor
College of Physicians & Surgeons, Columbia University
Leonard N. Horowitz, M.D.
Associate Professor of Medicine
Hahnemann University
Raymond J. Lipicky, M.D.
Acting Director, Division of Cardio-Renal Drug Products
Food and Drug Administration
E. Neil Moore, D.V.M., Ph.D.
Associate Professor of Medicine
University of Pennsylvania
ix
Joel Morganroth, M.D.
Professor of Medicine and Pharmacology
Hahnemann University
Gordon W. Pledger, Ph.D.
Group Leader, Statistical Evaluation Branch
Division of Biometrics
Food and Drug Administration
Craig M. Pratt, M.D.
Assistant Professor of Medicine
Baylor College of Medicine
Glenn A. Rahmoeller
Acting Director, Division of Cardiovascular Devices
Food and Drug Administration
John C. Somberg, M.D.
Assistant Professor of Medicine and Molecular Pharmacology
Albert Einstein College of Medicine
Scott R. Spielman, M.D.
Associate Professor of Medicine
Hahnemann University
Robert Temple, M.D.
Acting Director, Office of Drug Research & Review
Food and Drug Administration
August M. Watanabe, M.D.
Professor and Chairman, Department of Medicine
Professor of Pharmacology, Indiana University Medical Center
Roger A. Winkle, M.D.
Associate Professor of Medicine
Stanford University Medical Center
Raymond L. Woosley, M.D., Ph.D.
Associate Professor of Medicine and Pharmacology
Vanderbilt University
Douglas P. Zipes, M.D.
Professor of Medicine
Indiana University School of Medicine
In October, 1980 we convened our first Symposium on
New Drugs to evaluate new antiarrhythmic agents. The
participants comprised members of the Food and Drug
administration, the academic community and the research
divisions of the pharmaceutical industry. Five years ago,
there were a host of new antiarrhythmic agents being
evaluated in the United States in which basic research
design questions and approaches were so unclear and confus
ing that we hoped the discussions generated would lend new
guidlines to the evaluation process. We also believed that
this Forum might help speed to market new antiarrhythmic
agents to improve the drug armamentarium of physicians in
the United States. Antiarrhythmic agents are used to treat
patients with cardiac arrhythmias including those exhibiting
symptoms from hemodynamic consequences due to life
threatening ventricular arrhythmias as well as patients with
no symptoms from ventricular arrhythmias that increase the
risk of sudden cardiac death. Treatment for this later group
is offered with the hope that the abolition of the
ventricular arrhythmias will be prophylactic against sudden
death.
This fifth annual Symposium on New Drugs and Devices
has returned again to its origin by selecting the topic of
new antiarrhythmic agents and devices. Over the past five