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Atherothrombosis in
Clinical Practice
O
A C L
OXFORD AMERICAN CARDIOLOGY LIBRARY
This material is not intended to be, and should not be considered, a substitute for medi-
cal or other professional advice. Treatment for the conditions described in this material
is highly dependent on the individual circumstances. While this material is designed to
offer accurate information with respect to the subject matter covered and to be cur-
rent as of the time it was written, research and knowledge about medical and health
issues are constantly evolving, and dose schedules for medications are being revised
continually, with new side effects recognized and accounted for regularly. Readers must
therefore always check the product information and clinical procedures with the most
up-to-date published product information and data sheets provided by the manufactur-
ers and the most recent codes of conduct and safety regulation. Oxford University
Press and the authors make no representations or warranties to readers, express or
implied, as to the accuracy or completeness of this material, including without limita-
tion that they make no representations or warranties as to the accuracy or effi cacy of
the drug dosages mentioned in the material. The authors and the publishers do not
accept, and expressly disclaim, any responsibility for any liability, loss, or risk that may
be claimed or incurred as a consequence of the use and/or application of any of the
contents of this material.
The Publisher is responsible for author selection and the Publisher and the Author(s)
make all editorial decisions, including decisions regarding content. The Publisher and
the Author(s) are not responsible for any product information added to this publication
by companies purchasing copies of it for distribution to clinicians.
O A C L
OXFORD AMERICAN CARDIOLOGY LIBRARY
Atherothrombosis
in Clinical Practice
Edited by
Deepak L. Bhatt , MD, MPH
Professor of Medicine, Harvard Medical School
Chief of Cardiology, VA Boston Healthcare System
Director, Integrated Interventional Cardiovascular Program
Brigham and Women’s Hospital and VA Boston Healthcare System
Senior Investigator, TIMI Study Group
Boston, Massachusetts
Series Editor
Ragavendra R. Baliga, MD, MBA,
FACC, FRCP
Associate Director of Cardiovascular Medicine
The Ohio State University Medical Center
Columbus, Ohio
1
1
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Published in the United States of America by
Oxford University Press
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© Oxford University Press 2013
All rights reserved. No part of this publication may be reproduced, stored in a
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Inquiries concerning reproduction outside the scope of the above should be sent to the
Rights Department, Oxford University Press, at the address above.
You must not circulate this work in any other form
and you must impose this same condition on any acquirer.
Library of Congress Cataloging-in-Publication Data
Atherothrombosis in clinical practice/[edited by] Deepak L. Bhatt.
p. ; cm.—(Oxford American cardiology library)
Includes bibliographical references and index.
ISBN 978 –0–19–997675–1 (alk. paper)
I. Bhatt, Deepak L. II. Series: Oxford American cardiology library.
[DNLM: 1. Atherosclerosis. 2. Coronary Thrombosis. WG 550]
RC692
616.1′36—dc23 2013003698
9 8 7 6 5 4 3 2 1
Printed in the United States of America
on acid-free paper
https://t.me/med1917
v
Disclosures
Gregory Y. H. Lip, MD, has served as a consultant for Bayer, Astellas, Merck,
AstraZeneca, Sanofi, BMS/Pfizer, Daiichi-Sankyo, Biotronik, Portola and
Boehringer Ingelheim and has been on the speakers bureau for Bayer, BMS/
Pfi zer, Boehringer Ingelheim, and Sanofi Aventis.
Deepak L. Bhatt discloses the following relationships—Advisory Board: Elsevier
Practice Update Cardiology, Medscape Cardiology; Board of Directors: Boston
VA Research Institute, Society of Chest Pain Centers; Chair: American Heart
Association Get With The Guidelines Science Subcommittee; Honoraria:
American College of Cardiology (Editor, Clinical Trials, Cardiosource), Duke
Clinical Research Institute (clinical trial steering committees), Slack Publications
(Chief Medical Editor, Cardiology Today Intervention), WebMD (CME steering
committees); Other: Senior Associate Editor, Journal of Invasive Cardiology;
Data Monitoring Committees: Population Health Research Institute; Research
Grants: Amarin, AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Medtronic,
Sanofi Aventis, The Medicines Company; Unfunded Research: FlowCo,
PLxPharma, Takeda.
Patrick Collier and Brian Griffi n have no disclosure.
Yousif Ahmad has no disclosure.
Michelle L. O’Donoghue has received grant support through the TIMI Study
Group from Astra Zeneca and GlaxoSmithKline.
Amy Sarma has no disclosure.
Alexandros Briasoulis has no disclosure.
George Bakris-Consultant: Medtronic, Relapsya, AbbVie, Takeda, Daichi-
Sankyo, Boeringher Ingelheim, GSK, Janssen Investigator Initiated grants-Takeda.
Kathleen Yip has no disclosure.
Flavio de Souza Brito has no disclosure.
Renato D. Lopes has received grants, honoraria and travel expenses from
Bristol-Myers Squibb.
Matthew T. Roe has received grants from Eli Lilly & Company, KAI
Pharmaceuticals, and Sanofi -Aventis. He is a consultant for Bristol-Myers Squibb,
Eli Lilly & Company, Glaxo Smith Kline, Merck & Co., Janssen Pharmaceuticals,
Daiichi-Sankyo and Regeneron. He has received honoraria for educational lec-
tures from AstraZeneca and Janssen Pharmaceuticals.
Andrew T. Yan has received research grants and honoraria from Sanofi Aventis
and Bristol-Myers Squibb.
Chintan Patel, Roger S. Blumenthal, and Seth S. Martin have no disclosure.
https://t.me/med1917
To my wife Shanthala and to my sons Vinayak, Arjun, Ram, and Raj for all their
love and support while I am away taking care of patients with atherothrombosis
or researching new treatments for it.
https://t.me/med1917
Contents
Preface ix
Contributors xi
1. Atherothrombosis
1
Basem Elbarouni and Andrew T. Yan
2. Coronary Artery Disease
19
Flavio de Souza Brito, Renato D. Lopes, and Matthew T. Roe
3. Valvular Heart Disease
37
Patrick Collier and Brian Griffi n
4. Cerebrovascular Disease: Ischemic Syndromes
Due to Atherothrombosis
49
Mark J. Alberts
5. Atrial Fibrillation
65
Yousif Ahmad and Gregory Y. H. Lip
6. Peripheral Artery Disease
79
Amjad AlMahameed
7. Lipid-Modifying Therapy
95
Chintan Patel, Roger S. Blumenthal, and Seth S. Martin
8. Antithrombotic Therapy
111
Amy Sarma and Michelle L. O’Donoghue
9. Treatment of Primary Hypertension
129
Alexandros Briasoulis and George Bakris
10. Therapy for Type 2 Diabetes
145
Kathleen Yip and Sangeeta Kashyap
Index 159
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ix
Preface
Atherothrombosis is the coupling of atherosclerosis and thrombosis, leading
to the majority of preventable deaths in the modern world. The medical, eco-
nomic, social, and societal consequences of atherothrombosis are enormous. It
touches upon many lives either directly or indirectly. For example, families can
be devastated by the loss of a primary breadwinner at a young age from a heart
attack or stroke, or by having to care for an older parent who is unable to walk
due to disabling peripheral artery disease. All health care practitioners need to
know about atherothrombosis, as it is so commonly encountered. Therefore,
it is anticipated this book will be of interest to a wide range of audiences.
Cardiologists, vascular medicine specialists, neurologists, general physicians,
cardiac and vascular surgeons, physicians-in-training, and allied health profes-
sionals may all be particularly interested.
This book focuses upon the many clinical manifestations of atherothrom-
bosis and therapies that currently exist, with a focus on evolving therapeu-
tic approaches. First, atherothrombosis is defi ned and the epidemiology is
explored. Then, the specifi c manifestations of atherothrombosis (coronary
artery disease, valvular heart disease, cerebrovascular disease, atrial fi bril-
lation, peripheral artery disease) are covered by distinguished experts in the
fi eld. Next, specifi c medications are discussed, with an emphasis on innovative
therapies and investigational agents. Novel and experimental lipid-modifying,
anti-infl ammatory, antiplatelet, and anticoagulant agents are covered. State-of-
the-art treatment of hypertension and diabetes is described succinctly. Lifestyle
modifi cation, medical therapies, and, where appropriate, invasive modalities
are discussed. Controversies in areas such as cholesterol management and gly-
cemic control are summarized. There is ample use of tables and fi gures to
highlight key concepts. The emphasis is on where the fi eld of atherothrombosis
is heading, with a comprehensive review of relevant prior data.
I would like to thank all the authors, who were very creative in their
approaches to a complex topic. I am additionally appreciative of the fact that
they were all timely in their chapter submissions—quite rare among active,
busy clinician-researchers! Thus, much of the information presented is rela-
tively new. I am very grateful to Oxford University Press and, in particular, the
assistant editor Rebecca Suzan and the senior editor Andrea L. Seils. I would
also like to thank the series editor, Ragavendra R. Baliga, MD, MBA, for inviting
me to edit a book on the exciting and evolving topic of atherothrombosis. My
hope is that readers will fi nd this an educational and enjoyable book that is use-
ful in both clinical practice and investigation.
Deepak L. Bhatt, MD, MPH
https://t.me/med1917
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