Online Appendix for the following June 20 JACC article
TITLE: A Randomized Trial to Evaluate the Relative Protection Against PostPercutaneous Coronary Intervention Microvascular Dysfunction, Ischemia, and
Inflammation Among Antiplatelet and Antithrombotic Agents: The PROTECT–TIMI-30
Trial
AUTHORS: C. Michael Gibson, MS, MD, TIMI Study Group, Cardiovascular Division,
Brigham and Women’s Hospital and the Department of Medicine, Harvard Medical
School, Boston, Massachusetts, David A. Morrow, MD, MPH, TIMI Study Group,
Cardiovascular Division, Brigham and Women’s Hospital and the Department of
Medicine, Harvard Medical School, Boston, Massachusetts, Sabina A. Murphy, MPH,
TIMI Study Group, Cardiovascular Division, Brigham and Women’s Hospital and the
Department of Medicine, Harvard Medical School, Boston, Massachusetts, Theresa M.
Palabrica, MD, Millennium Pharmaceuticals, Inc., Cambridge, Massachusetts, Lisa K.
Jennings, PhD, University of Tennessee, Knoxville, Tennessee, Peter H. Stone, MD,
TIMI Study Group, Cardiovascular Division, Brigham and Women’s Hospital and the
Department of Medicine, Harvard Medical School, Boston, Massachusetts, Henry H. Lui,
MD, APEX Cardiology, Jackson, Tennessee, Thomas Bulle, MD, Cardiovascular
Associates, Kingsport, Tennessee, Nasser Lakkis, MD, Ben Taub Hospital, Houston,
Texas, Richard Kovach, MD, Our Lady of Lourdes Medical Center, Camden, New
Jersey, David J. Cohen, MD, MSC, Beth Israel Deaconess Medical Center, Boston,
Massachusetts, Polly Fish, BS, TIMI Study Group, Cardiovascular Division, Brigham
and Women’s Hospital and the Department of Medicine, Harvard Medical School,
Boston, Massachusetts, Carolyn H. McCabe, BS, TIMI Study Group, Cardiovascular
Division, Brigham and Women’s Hospital and the Department of Medicine, Harvard
Medical School, Boston, Massachusetts, Eugene Braunwald, MD, TIMI Study Group,
Cardiovascular Division, Brigham and Women’s Hospital and the Department of
Medicine, Harvard Medical School, Boston, Massachusetts, for the TIMI Study Group
APPENDIX I
TIMI Study Chairman: Dr. Eugene Braunwald; TIMI Study Director: Ms. Carolyn H.
McCabe.
Principal Investigator: Dr. C. Michael Gibson; Co-Principal Investigator: Dr. David
Morrow; Project Manager: Ms. Polly Fish.
Data Safety Monitoring Board: Dr. W. Douglas Weaver, Henry Ford Hospital; Dr.
Judith S. Hochman, New York University School of Medicine; Dr. David Holmes, Mayo
Clinic.
Data Management: Harvard Clinical Research Institute: Ms. Alison Osattin and Mr. Kiu
Li; TIMI Data Coordinating Center: Dr. C. Michael Gibson, Ms. Sabina A. Murphy, Ms.
Jacki Buros and Ms. Amy Sun.
Core Laboratories: TIMI Angiographic Core Laboratory: Dr. C. Michael Gibson, Dr.
Daniela Budiu and Mr. Allen Chang; Ambulatory ECG Core Laboratory: Dr. Peter Stone,
Dr. Benjamin Scirica, Ms. Gail MacCallum, and Ms. Michelle Lucier; TIMI Biomarker
Core Lab, Brigham and Women's Hospital: Dr. David A. Morrow, Dr. Nader Rifai, Ms.
Gail Borkowski, and Mr. Gary Bradwin; UTHSC Vascular Biology Center of Excellence:
Dr. Lisa Jennings and Ms. Mary Jacoski.
Sponsor Medical Monitor: Dr. T. Palabrica, Millennium Pharmaceuticals.
Investigators: Canada: Dr. Michel Joyal and Mr. Marquis Grenier, Montreal Heart
Institute; Dr. Benoit Tremblay and Ms. Claude Darveau, Centre Hospitalier Universitaire
de Quebec (CHUQ); United States: Dr. Henry Lui and Ms. Donna Manns, Apex
Cardiology; Dr. Renato Santos and Ms. Ann Louise Armstrong, Cardiovascular
Associates, Pc; Dr. Nasser Lakkis and Mr. Jeremy Bobek, Ben Taub Hospital; Dr.
Richard Kovach and Ms. Donna Palazzo, Associated Cardiovascular Consultants; Dr.
David Cohen and Ms. Theresa Bishop, Beth Israel Deaconess Medical Center; Dr. John
A. McPherson and Ms. Pamela Thompson, The Heart Group; Dr. Alan Niederman and
Ms. Terri Kellerman, North Ridge Medical Center; Dr. Robert Feldman and Ms. Susan
Berry Munroe, Regional Medical Center; Dr. Howard Herrmann and Ms. Terry Mannion,
University of Pennsylvania; Dr. Albert Chan and Ms. Barbara Hirstius, Oschner Institute;
Dr. William French and Ms. Olga Barillas, Harbor-UCLA Medical Center; Dr. James
Blankenship and Ms. Deb Zimmerman, Geisinger Medical Center; Dr. Joseph Kozina
and Ms. Sarah Bordash, Mercy Heart Institute; Dr. Tift Mann and Ms. Tanya Smallwood,
Wake Medical Center; Dr. John Katopodis and Ms. Patty Knap, Tallahassee Memorial
Heart and Vascular Institute; Dr. Paul Gordon and Ms. Nora Wright, Miriam Hospital;
Dr. Gene Langevin and Mr. Larry Neff, Freeman Hospital; Dr. Manish Chauhan and Ms.
Judy Pendleton, Lahey Medical Center; Dr. Carey Kimmelstiel and Ms. Sandra Galvin,
New England Medical Center; Dr. David H. Wohns and Ms. Susan Rosema, Spectrum
Health-Cook Research Dept.; Dr. Samuel Butman and Ms. Barbara Lambeth, University
of Arizona Heart Center; Dr. Ernesto Rivera and Ms. Shandee Tolleson, Northwest Texas
Healthcare System; Dr. Paul Tolerico and Ms. Barb Delio-Cox, York Hospital; Dr. Fred
Ling and Ms. Lori Caufield, University of Rochester; Dr. Andreas Wali and Ms. Susan
Kilbride, Harrisburg Hospital; Dr. Bruce Graham and Ms. Claudia Fenoglio, Ball
Memorial Hospital; Dr. Julian Esteban and Mr. Steven Ball, UMass, Memorial Medical
Center; Dr. Joshua Kieval and Ms. Jamie Kosik, FL Cardiovascular Research at JFK Ctr;
Dr. Steven Yakubov and Ms. Cher Mitchell, Riverside Methodist Hospital; Dr. William
Felten and Ms. Wynona Packard, Covenant Hospital; Dr. Robert Fishman and Ms. Tina
Cullen, Bridgeport Hospital; Dr. Glenn Levine and Ms. Tracy Ferrando, Houston
VAMC; Dr. Michael Miller and Ms. Doris Bembridge, Pit County Memorial Hospital;
Dr. Mark Greenberg and Ms. Francis Paulison, Montefiore Medical Center; Dr. Ralph
Vicari and Ms. Mary Howard, Holmes Regional Medical Center; Dr. Matthew French
and Mr. Andrew Scroggs, The Care Group; Dr. John Warner and Ms. Sharon Baker,
Parkland Health and Hospital System; Dr. Pierre Istfan and Ms. Ann Louise Armstrong,
Wellmont Bristol Regional Medical Center; Dr. Howard Haber and Ms. Elizabeth
Tiffany-Ellis, Pennsylvania Hospital; Dr. Bruce Klugherz and Ms. Jean Marie Markham,
Abington Hospital; Dr. Jeffrey Popma and Ms. Rachele Monbouquette, Brigham and
Women’s Hospital; Dr. Andrew Rees and Ms. Aimee Yoches, Our Lady of the Lake
Regional Medical Center; Dr. Magdi Ghali and Ms. Jamie Welch, Iowa Methodist
Medical Center; Dr. Paul Gurbel and Mr. Kevin Bliden, Sinai Hospital; Dr. Ralph
Millsaps and Ms. Jan Ernest, St. Mary’s Medical Center; Dr. Harry Colfer and Ms.
JoAnn Haderer, Northern Michigan Hospital; Dr. David Churchill and Ms. Anne
Courtney-Eighmy, Arkansas Institute for Research and Education; Dr. Dave Roberts and
Ms. Beverly Seiler, Sutter Memorial Hospital; Dr. Mike Ayres and Ms. Vicki Rhule,
Knoxville Heart Group; Dr. John Messenger and Ms. Kathy Kioussopoulos, Department
of VA Medical Center; Dr. Joseph Puma and Ms. Carolyn Payne, New York Methodist
Hospital; Dr. Sanjay Khanal and Ms. Julieanne Longlade, Henry Ford Hospital; Dr. Jose
Perez and Ms. Peggy Bielke, South Texas Cardiovascular Consultants; Dr. Lisa
Abrahams and Ms. Annette Page, St. Mary’s/ Duluth Clinic Health System; Dr. Robert
Greene and Ms. Vickie Nolan, Alta Bates Medical Center; Dr. C. David Hassel and Ms.
Diana Hartley, Jacksonville Heart Center; Dr. John Messenger and Ms. Kathy
Kioussopoulos, University of Colorado Health Sciences Center; Dr. Marc Schweiger and
Ms. Mary Nabors, Baystate Medical Center; Dr. Fayez Shamoon and Ms. Linda Gennari,
St. Michael's Hospital; Dr. David Zhao and Ms. Kristie Hanley, Vanderbilt Medical
Center; Dr. Raymond Magorien and Ms. Kelly Niedert, Ohio State University Medical
Center; Dr. Nathaniel Niles and Ms. Susan Kennedy, Dartmouth Hitchcock Medical
Center; Dr. James Beckman and Ms. Ann Coombs, BHRI; Dr. Vibhuti Singh and Ms.
Michelle Richardson, Bayfront Medical Center; Dr. Nicholas Xenopoulos and Ms.
Elizabeth Cooke, Jewish Hospital; Dr. Ali Amkieh and Ms. Bronwyn Westling,
Advanced Medical Research; Dr. John Corbelli and Ms. Beth Cooke, Buffalo Cardiology
+ Pulmonary Associates; Dr. John Lopez and Ms. Peggy Bennett, University of Chicago;
Dr. Joseph Gelormini and Ms. Corey Mankowsli, Buffalo Heart Group; Dr. Karan Reddy
and Ms. Shannon Harrison, Florida Hospital; Dr. Benjamin Lee and Ms. Janice Lavoie,
Washington Hospital Center; Dr. Craig Siegel and Ms. Shannon Semple, The Heart
Center of Eastern Carolina; Dr. Barry Molk and Ms. Karen Bickett, Aurora Denver
Cardiology; Dr. Martin Frey and Ms. Joelynn Selby, Sarasota Memorial Hospital; Dr. Ian
Gilchrist and Ms. Terri Zimmerman, Penn State Milton S. Hershey Medical Center; Dr.
Elias Iliadis and Ms. Anne Yannes, Cooper Health System; Dr. Seth Krauss and Ms.
Laurie Heaney, Providence Medical Center; Dr. Kevin Miller and Ms. Tina Volz,
Cardiology Associates; Dr. Pinak Shah and Ms. Annie Connors, St. Elizabeth’s Medical
Center; Dr. Nicolas Shammas and Ms. Penny Stoakes, Genesis Medical Center; Dr.
William Scott Sheldon and Ms. Lori Pronesti, North Ohio Research; Dr. Thomas Shook
and Ms. Stephanie Hiller Mullin, Los Angeles Cardiology Associates; Dr. William Dillon
and Ms. Julie Hanrahan, Baptist Hospital East; Dr. George Brodell and Ms. Marci
Whorley, Lafayette Heart Institute; Dr. W. Paul Biddle and Ms. Lois Rasmussen,
Creighton Cardiac Center; Dr. Muhammed Yasin and Ms. Kathy Stilwell, Integris
Southwest Medical Center; Dr. Marc Schrode and Ms. Laurie Paletta, Southwest General
Health Center; Dr. Sanjay Singh and Ms. Jean Sesing, Waukesha Memorial Hospital; Dr.
Jose Perez and Ms. Terri Pointon, Texan Heart Hospital; Dr. Steven Steinhubl and Ms.
Sharon Castina, University of North Carolina; Dr. John Bedotto and Ms. Kathy Azinger,
Sunrise Hospital and Medical Center; Dr. Kenneth Fromkin and Ms. Kim Thinas,
Cleveland Clinic- Florida; Dr. Zubair Jafar and Ms. Patty O’Brien, Vassar Brothers
Hospital; Dr. Roderick Meese and Ms. Cheryl Rasor, Mother Francis Regional Health
Care Center; Dr. Timothy Grady and Mr. Jeff Kaliebe, Wausau Hospital; Dr. William
Penny and Ms. Pat James, VA San Diego Medical Center; Dr. H. Vernon Anderson and
Ms. Carol Underwood, University of Texas Medical School-Houston; Dr. Paul Casale
and Ms. Marsha Adams, Lancaster General Hospital; Dr. Stephen Halpern and Ms. Tessa
Murray, Radiant Research Santa Rosa; Dr. John Warner and Ms. Sharon Baker, St. Paul
University Hospital; Dr. Dale Wortham and Ms. Cindy Langley, Knoxville
Cardiovascular Group; Dr. Imran Dotani and Ms. Shelly Napier, Indiana Heart
Physicians; Dr. Stephen Broadwater and Ms. Marcia Edwards, Augusta Cardiology
Clinic.
APPENDIX II
For MI after 24 h post-PCI but before the cardiac biomarker assayed has returned to
normal from the index event, a patient must meet criteria 1 and 2 or criterion 3 alone of
the following: 1) Cardiac biomarker re-elevation defined as, increase by at least 50% over
the previous value and documentation that the cardiac biomarker was decreasing prior to
the suspected recurrent MI; and 2) at least one of the following additional supportive
criteria: a) New ischemic discomfort ≥20 min at rest or b) new hemodynamic
decompensation requiring treatment with
IV inotropes or IABP; or c) one of the
following ECG changes: i) new or re-elevation of ST-segments ≥0.2 mV (80 ms after the
J-point) in ≥2 contiguous precordial leads or ≥0.1 mV in ≥2 adjacent limb leads; or ii)
Development of new, abnormal Q waves in ≥2 contiguous precordial leads or ≥2 adjacent
limb leads considered to be distinct from the evolution of the index MI; or iii) new left
bundle branch block; or 3) pathologic findings of a new acute MI felt to be distinct from
the index MI.
After 24 h post-PCI and after cardiac biomarker assayed has been documented to return
to normal from the index event, a subject must meet criteria 1 and 2 or criterion 3 alone
or criterion 4 alone: 1) typical cardiac biomarker rise and fall with the following degrees
of elevation accepted as biochemical evidence of myocardial necrosis: a) troponin T or I:
maximal concentration > cutpoint for MI; or b) one CK-MB > ULN; c) total CK:
maximal concentration >2 × ULN; and 2) At least one of the following additional
supportive criteria: a) ischemic discomfort or equivalent at rest lasting ≥20 min; or b) STT wave changes indicative of ischemia; 3) development of new, abnormal Q waves in ≥2
contiguous precordial leads or ≥2 adjacent limb leads, considered to be distinct from the
evolution of the index MI; or 4) pathologic findings of a new acute MI felt to be distinct
from the index MI.
MI within 24 h after CABG was defined as either: 1) one CK-MB >10 × ULN and, if the
pre-CABG CK-MB was > ULN, both an increase by at least 50% over the previous value
and documentation that CK-MB was decreasing prior to the suspected recurrent MI; 2)
one CK-MB >5 × ULN and if the pre-CABG CK-MB was > ULN, both an increase by at
least 50% over the previous value and documentation that CK-MB was decreasing prior
to the suspected recurrent MI and development of new, abnormal Q waves in >2
contiguous precordial leads or >2 adjacent limb leads, considered to be distinct from the
evolution of the index MI; or 3) pathologic findings of a new acute MI felt to be distinct
from an index MI.