SUPPLEMENTAL APPENDIX
TABLE OF CONTENTS
Online Table 1. List of Study Investigators and Sites
Online Table 2. Members of the TERISA Publications Committee
Online Table 3. Enrollment in TERISA by Country
Online Table 4. Baseline Characteristics of Patients by Geographic Region
Online Table 5. Results for the outcomes of angina frequency and SL NTG use using arithmetic
means.
Online Figure 1. Novel Electronic Diary
Online Figure 2. Flow Diagram of Study Protocol in TERISA
Online Figure 3. Weekly Angina Frequency and Weekly SL NTG Use by Study Group,
Stratified by Geographic Region
1
Online Table 1. List of Study Investigators and Sites
Country/Investigator
Study Site/City/State
Enrolled/
Randomized
BELARUS
Mikhailova, Elena, MD
Institution “Gomel Regional Clinical Hospital”/Gomel
1/1
Mrochek, Alexander, MD PhD
State Institution Republican Scientific/Minsk
2/0
Baurenski, Lyubomir, MD
National Cardiology Center/Sofia
6/6
Mincheva, Valentina, MD PhD
National Multiprofile Treatment Hospital “Tsar Boris III”/Sofia
7/6
Raev, Dimitar, MD PhD
Diagnostic Consultative Center “Ascendent”/Sofia
2/2
Ramshev, Konstantin, MD PhD
Military Medical Academy/Sofia
5/5
Stoikov, Anastas, MD
Multiprofile Hospital for Active Treatment “Vita”/Sofia
1/1
Gupta, Anil, MD
Dr Anil K Gupta Medicine Professional Corp/Toronto, ON
1/1
Henein, Sam, MD
SKDS Research Inc/Newmarket, ON
3/2
O'Mahony, Michael, MD
London Road Diagnostic Clinic and Medical Centre/Sarnia, ON
1/0
Tardif, Jean-Claude, MD
Montreal Heart Institute/Montreal, QC
1/0
Brabec, Tomas, MD
Vojenska Nemocnice Brno/Brno
1/1
Cermak, Ondrej, MD
Nemocnice Slany/Slany
1/1
Jerabek, Ondrej, MD
Centrum Klinického Výzkumu, s.r.o/Príbram
3/3
Povolny, Jiri, MD
Cardiocentrum Kladno s.r.o/Kladno
1/0
Riedlbauchova, Lucie, MD
Fakultní Nemocnice v Motole/Praha
1/1
Zidkova, Eva, MD
Corintez s.r.o/Praha
3/3
BULGARIA
CANADA
CZECH REPUBLIC
GEORGIA
Chapidze, Gulnara, MD PhD
Academician G. Chapidze Emergency Cardiology Centre LTD/
Tbilisi
19/17
Chumburidze, Vakhtang, MD PhD
Academician G. Chapidze Emergency Cardiology Centre LTD/
Tbilisi
15/15
Khintibidze, Irakli, MD PhD
EOPL Tbilisi State Medical University/Tbilisi
Kobulia, Bondo, MD PhD
Cardio-Reanimation Centre LTD/Tbilisi
15/15
Megreladze, Irakli, MD PhD
Amtel Hospital First Clinical LLC/Tbilisi
6/5
Melia, Anzor, MD
Cardiological Clinic “Guli” LTD/Tbilisi
6/5
Paposhvili, Kakhi, MD
#2 Multiprofile Clinical Hospital of Tbilisi/Tbilisi
4/3
Shaburishvili, Tamaz, MD PhD
Tbilisi Heart and Vascular Clinic LTD/Tbilisi
5/5
12/11
GERMANY
Maier, Lars, MD PhD
Universitatsmedizin Gottingen/Gottingen
2/1
Salbach, Peter, MD
Praxis Fur Innere Medizin/Mannheim
1/1
Wolde, Claus-Henning, MD
Gemeinschaftspraxis Fur Kardiologie, Arztehaus West/
Heidelberg
1/1
Assaf Harofeh Medical Center/Zerifin
3/1
ISRAEL
Blatt, Alex, MD
2
Online Table 1. List of Study Investigators and Sites
Enrolled/
Randomized
Country/Investigator
Study Site/City/State
Katz, Amos, MD
Barzilai Medical Center/Ashkelon
Klutstein, Marc, MD
Shaare Zedek Medical Center/Jerusalem
3/3
Kracoff, Oscar, MD
Kaplan Medical Center/Rehovot
6/3
Marmor, Alon, MD PhD
Ziv Medical Center/Safed
8/4
Bednarski, Janusz, MD
Samodzielny Publiczny Specjalistyczny Szpital Zachodni im.
Jana Pawla II/Grodzisk Mazowiecki
11/9
Bochenek, Anna, MD
Centrum Badawcze Wspólczesnej Terapii; Prywatny Gabinet
Lekarski/Warszawa
15/14
Bryniarski, Leszek, MD PhD
Specjalistyczna Praktyka Lekarska Leszek Bryniarski/ Kraków
19/11
Chmielak, Zbigniew, MD PhD
Instytut Kardiologii im. Prymasa Tysiaclecia Stefana Kardynala
Wyszynskiego/Warszawa
12/10
Dabrowska, Magda, MD
Synexus SCM Sp z o.o Oddzial Warszawie/Warszawa
5/2
Dulak, Elzbieta, MD PhD
NZOZ Sródmiescie Sp z o.o./Gdynia
11/8
Helon, Henryk, MD
NZOZ Revita Poradnia Kardiologiczna/Kraków
4/4
Kania, Grzegorz, MD
Niepubliczny Zaklad Opieki Zdrowotnej Przychodnia Zdrowia
“Zadebie”/Skierniewice
21/18
Konieczny, Marek, MD
KO-MED Marek Konieczny/Pulawy
17/13
Nessler, Jadwiga, MD PhD
Krakowski Szpital Specjalistyczny im. Jana Pawla II w
Krakowie/Kraków
2/1
Polonski, Lech, MD PhD
Slaskie Centrum Chorób Serca w Zabrzu/Zabrze
3/2
Szwed, Hanna, MD PhD
Instytut Kardiologii im. Prymasa Tysiaclecia Stefana Kardynala
Wyszynskiego/Warszawa
1/1
Agafina, Alina, MD PhD
Saint-Petersburg State Budget Healthcare Institution “City
Hospital #40 of Kurortniy District”/Sestroretsk, St. Petersburg
8/5
Andreev, Denis, MD PhD
State Budget Educational Institution of High Professional
Education First Moscow State Medical University n.a. I.M.
Sechenov of Ministry of Healthcare of Russian Federation/
Moscow
31/28
Arkhipov, Mikhail, MD PhD
Sverdlovsky Regional Clinical Hospital of Wars Veterans/
Ekaterinburg
20/17
Barbarash, Olga, MD PhD
Municipal Budgetary Institution of Healthcare/Kemerovo
24/22
Chumakova, Galina, MD PhD
Regional State Budgetary Healthcare Institution/Barnaul
25/25
Eltishcheva, Vera, MD PhD
Medical centre "Delis", LLC/Kirovsk
15/10
Fitilev, Sergey, MD PhD
State Budget Healthcare Institution of Moscow/Moscow
18/13
Giorgadze, Marina, MD PhD
Autonomous Healthcare Institution of Voronezh Region/
Voronezh
11/11
Gordeev, Ivan, MD PhD
State Budget Healthcare Institution of Moscow "City Clinical
hospital #15 named after O.M. Filatov" of Healthcare
Department of Moscow/Moscow
28/20
13/13
POLAND
RUSSIA
3
Online Table 1. List of Study Investigators and Sites
Enrolled/
Randomized
Country/Investigator
Study Site/City/State
Gordienko, Alexander, MD PhD
Federal State Public Military Educational Institution “Medical
Military Academy n.a. S.M. Kirov” of Ministry of Defense of
Russia/St. Petersburg
29/24
Govorin, Anatoly, MD PhD
Curative-Diagnostic Clinic of State Budgetary Education
Institution of High Professional Education “Chita State Medical
Academy” of Ministry of Health/Chita
33/24
Ivanov, Sergey, MD
State Budgetary Healthcare Institution of Novosibirsk Region
“State Novosibirsk Regional Clinical Hospital”/Novosibirsk
11/10
Ivanova, Tatyana, MD
Moscow State Healthcare Institution City Clinical Hospital #71
of Moscow Healthcare Department/Moscow
54/49
Kostenko, Victor, MD PhD
St. Petersburg State Budgetary Healthcare Institution
"Municipal Out-patient Clinic #109"/St. Petersburg
25/25
Koziolova, Natalya, MD PhD
State Institution of Healthcare Perm Regional Hospital for War
Veterans/Perm
11/11
Kozyrev, Oleg, MD PhD
State Budget Educational Institution of High Professional
Education Smolensk State medical Academy of Ministry of
Health and Social Development of Russian Federation on the
base of Regional State Budget Healthcare Institution “Clinical
Hospital of Emergency Medicine”/Smolensk
8/7
Libov, Igor, MD PhD
Moscow state Budget Healthcare Institution “City Clinical
Hospital n.a. S.P. Botkin” of Moscow Healthcare
Department/Moscow
8/8
Malygin, Alexander, MD PhD
The State Healthcare Institution of Yaroslavl oblast the Clinical
Hospital #8/Yaroslavl
18/13
Martsevich, Sergey, MD PhD
Federal State Budget Institution “State Scientific and Research
Center of Preventative Medicine” of Ministry of Health of
Russian Federation/Moscow
14/12
Masin, Anatoly, MD PhD
Non-State Institution of Healthcare “Department Hospital on
Station Kemerovo of OAO “Russian Railway”/Kemerovo
6/6
Morozova, Tatiana, MD
State Budget Educational Institution of High Professional
Education First Moscow State Medical University n.a. I.M.
Sechenov of Ministry of Healthcare and Social Development of
Russian Federation;University Clinical Hospital #1/ Moscow
7/4
Obrezan, Andrey, MD PhD
International Medical Center “SOGAZ”/St. Petersburg
6/2
Oleynikov, Valentin, MD PhD
State Budget Healthcare Institution “Penza Regional Clinical
Hospital named after N.N. Burdenko”/Penza
Paltsman, Zhanna, MD
Medical Research Institute LLC/St. Petersburg
2/1
Panov, Alexey, MD PhD
Federal Heart, Blood and Endocrinology Centre n.a.
Almazov/St. Petersburg
9/9
Privalov, Dmitriy, MD PhD
State Budget Healthcare Institution “City Clinical Hospital #51
of Healthcare Department of Moscow”/Moscow
15/11
Privalova, Elena, MD PhD
State Budget Educational Institution of High Professional
Education First Moscow State Medical University n.a. I.M.
Sechenov of Ministry of Healthcare of Russian Federation,
University Clinical Hospital #1/Moscow
31/30
37/37
4
Online Table 1. List of Study Investigators and Sites
Enrolled/
Randomized
Country/Investigator
Study Site/City/State
Shogenov, Zaur, MD PhD
The State Budgetary Healthcare Institution of the City of
Moscow “The City Clinical Hospital #81 of the Department of
Public Health of the City of Moscow”/Moscow
Shvarts, Yury, MD PhD
Clinical Hospital named after S.R.Mirotvortsev/Saratov
Sinopalnikov, Alexander, MD
PhD
Moscow State Budget Healthcare Institution “City Clinical
Hospital n.a S.P. Botkin” of Moscow Healthcare Department/
Moscow
2/2
Sotnikova, Tatiana, MD PhD
Moscow State Budget Healthcare Institution “City Clinical
Hospital n.a S.P. Botkin” of Moscow Healthcare Department/
Moscow
9/9
Vaniev, Sergey, MD PhD
Federal State Budget Institution “Central Clinical Hospital with
Out-Patient Department” of Administration of President of
Russian Federation/Moscow
15/10
Yakushin, Sergey, MD PhD
State Budget Institution of Ryazan Region/Ryazan
19/18
Zhelninova, Tatiana, MD PhD
Federal Heart, Blood and Endocrinology Centre n.a.
Almazov/St. Petersburg
23/16
Zotov, Dmitriy, MD PhD
Saint-Petersburg State Healthcare Institution/St. Petersburg
19/17
Zrazhevsky, Konstantin, MD PhD
Saint-Peterburg State Budget Healthcare Institution “City
Hospital #38 named after n.a. Semashko”/St. Petersburg
24/20
7/1
19/17
SERBIA
Pavlovic, Katica, MD PhD
Institute of Cardiovascular Disease/Sremska Kamenica
2/2
Popovic, Dejana, MD PhD
Clinical Center Serbia/Belgrade
4/4
Dulkova, Katarina, MD
Kardiovaskularne Centrum, s.r.o/Bratislava
5/2
Dzupina, Andrej, MD
ALIAN, s.r.o/Bardejov
7/6
Hatalova, Katarina, MD
Cardioconsult, s.r.o/Bratislava
3/3
Nociar, Jan, MD
KARDIOMED, s.r.o/Lucenec
5/5
Pella, Daniel, MD PhD
CARDIO D&R, s.r.o/Kosice
6/5
Fras, Zlatko, MD PhD
University Medical Centre Ljubljana/Ljubljana
3/1
Kovac, Dusan, MD
General Hospital Murska Sabota, Rakican/Murska Sobota
2/0
Andrievskaya, Svetlana, MD PhD
SI Odessa Regional Cardiological Dispensary/Odessa
5/5
Barna, Olga, MD PhD
National Medical Academy of Postgraduate Education named
after P.L. Shupyk based on Day Time Hospital of
Administration of Medical Service and Rehabilitation of
“ARTEM” SHC/Kyiv
16/16
Batushkin, Valerii, MD PhD
Kyiv City Clinical Hospital #5/Kyiv
10/10
Bazylevych, Andriy, MD PhD
Lviv National Medical University named after Danylo
Halytsky/Lviv
SLOVAKIA
SLOVENIA
UKRAINE
9/7
5
Online Table 1. List of Study Investigators and Sites
Enrolled/
Randomized
Country/Investigator
Study Site/City/State
Karpenko, Oleksandr, MD PhD
Kyiv City Clinical Hospital #1/Kyiv
16/14
Kraiz, Igor, MD
Central Clinical Hospital of Ukrzaliznytsia/Kharkiv
26/25
Lishnevska, Viktoriia, MD PhD
SI “Institute of Gerontology of AMS of Ukraine”/Kyiv
10/10
Tseluyko, Vira, MD PhD
City Clinical Hospital #8/Kharkiv
22/21
Vatutin, Mykola, MD PhD
Donetsk National Medical University/Donetsk
15/14
UNITED STATES
Bareket, Yaron, MD
Cross County Cardiology/Edgewater, NJ
2/2
Challappa, Krishnan, MD
Central Cardiology Associates/Elizabethtown, KY
1/1
El-Hafi, Salah, MD
Med-Tech Research/Houston, TX
3/1
Giusti, Richard, MD
Clinical Research of Central Florida/Winter Haven, FL
1/0
Hage-Korban, Elie, MD
Kore CV Research/Jackson, TN
5/4
Hargrove, Joe, MD
Cardiology and Medicine Clinic 5315/Little Rock, AR
11/5
Jaffrani, Naseem, MD
Alexandria Cardiology Clinic/Alexandria, LA
1/0
Jones, Alonzo, MD
Columbus Cardiology Associates/Columbus, GA
6/2
Litt, Marc, MD
Baptist Heart Specialists/Jacksonville, FL
1/1
Nallasivan, Mani, MD
Merced Heart Associates/Merced, CA
1/0
Ponce, George, MD
Spectrum Clinical Research Institute, Inc/Moreno Valley, CA
7/4
Presser, Dale, MD
Clinical Trials Management, LLC/Mandeville, LA
2/0
Salacata, Abraham, MD
Endeavor Medical Research, PLC/Alpena, MI
2/0
Splaver, Adam, MD
South Florida Research Solutions, LLC/Hollywood, FL
4/3
Sprague, Amy, MD
Masters of Clinical Research Inc/Augusta, GA
1/0
VanHamersveld, Daniel, MD
Sacramento Heart and Vascular Research Ctr/Sacramento, CA
6/4
Vora, Kishor, MD
Research Integrity, LLC/Owensboro, KY
1/0
6
Online Table 2. Members of the TERISA Publications Committee
Name
Institution
Suzanne Arnold, MD MHA
St. Luke’s Mid America Heart Institute, Kansas City, MO
Ori Ben-Yehuda, MD
Gilead Sciences, Foster City, CA
Bernard Chaitman, MD
Saint Louis University, St. Louis, MO
Amos Katz, MD
Barzilai Medical Center, Ashkelon, Israel
Mikhail Kosiborod, MD
St. Luke’s Mid America Heart Institute, Kansas City, MO
Darren McGuire, MD MHSC
University of Texas Southwestern Medical Center, Dallas, TX
Ann Olmsted, PhD*
Gilead Sciences, Foster City, CA
Patrick Yue, MD
Gilead Sciences, Foster City, CA
*nonvoting member
7
Online Table 3. Enrollment in TERISA by Country
Country
Number of Subjects
Belarus
1
Bulgaria
18
Canada
3
Czech Republic
8
Georgia
75
Germany
3
Israel
23
Poland
89
Russia
537
Serbia
5
Slovakia
20
Slovenia
1
Ukraine
121
United States
23
Total
927
Number of subjects from each country who comprised the full
analytic sample, from which the efficacy analyses were derived
8
Online Table 4. Baseline Characteristics of Patients by Geographic Region
Russia/Ukraine/Belarus
n=659
Other
n=268
P
63.3±8.5
64.6±8.5
0.039
Men—no. (%)
388 (58.9%)
181 (67.5%)
0.014
White—no. (%)
659 (100.0%)
259 (96.6%)
<0.001
Hypertension—no. (%)
633 (96.2%)
250 (93.6%)
0.089
Dyslipidemia—no. (%)
491 (77.8%)
214 (84.9%)
0.017
Current smoking—no. (%)
102 (15.5%)
46 (17.2%)
0.525
Prior myocardial infarction—no. (%)
499 (76.4%)
183 (68.3%)
0.011
Prior angioplasty—no. (%)
200 (30.4%)
177 (66.3%)
<0.001
Prior bypass graft surgery—no. (%)
115 (17.5%)
57 (21.3%)
0.175
Duration of diabetes—yr
6.6±6.3
9.5±7.6
<0.001
HbA1c—%
7.3±1.5
7.3±1.5
0.561
Antidiabetic Medication—no. (%)
614 (93.2%)
248 (92.5%)
0.732
Insulin—no. (%)
107 (16.2%)
70 (26.1%)
<0.001
Age—yr
Antianginal medications
0.002
on 1—no. (%)
389 (59.0%)
129 (48.1%)
on 2—no. (%)
270 (41.0%)
139 (51.9%)
Beta blockers—no. (%)
588 (89.2%)
248 (92.5%)
0.125
Calcium channel blockers—no.
(%)
189 (28.7%)
78 (29.1%)
0.897
Long acting nitrates—no. (%)
226 (34.3%)
86 (32.1%)
0.520
Statins—no. (%)
544 (82.5%)
220 (82.1%)
0.868
Antiplatelet agents—no. (%)
581 (88.2%)
236 (88.1%)
0.965
ACE-I/ARBs—no. (%)
592 (89.8%)
222 (82.8%)
0.003
7.2±4.5
6.3±3.8
0.007
Weekly angina frequency, baseline
9
Online Table 5. Results for the outcomes of angina frequency and SL NTG use using
arithmetic means. Values are arithmetic means (95% confidence intervals).
Efficacy Endpoints
Ranolazine
(n=462)
Placebo
(n=465)
Angina frequency, baseline (number/wk)
6.8 (6.5-7.2)
7.0 (6.6-7.4)
Angina frequency, on treatment (number/wk)
4.5 (4.1-4.9)
5.2 (4.8-5.6)
SL-NTG use, baseline (number/wk)
4.2 (3.8-4.6)
4.6 (4.1-5.1)
SL-NTG use, on treatment (number/wk)
2.9 (2.5-3.3)
3.6 (3.1-4.1)
Primary Endpoint
Key Secondary Endpoint
10
Online Figure 1. Novel Electronic Diary
11
Online Figure 2. Flow Diagram of Study Protocol in TERISA
12
Online Figure 3. Weekly Angina Frequency (A) and Weekly SL NTG Use (B) by Study
Group, Stratified by Geographic Region
13
14