A randomized, parallel group, double-blind study of ticagrelor compared with aspirin for prevention of vascular events in patients undergoing coronary artery bypass graft operation: Rationale and design of the Ticagrelor in CABG (TiCAB) trial: An Investigator-Initiated trial.
BACKGROUND
For patients with coronary artery disease undergoing coronary bypass surgery, acetylsalicylic acid (ASA) currently represents the gold standard of antiplatelet treatment. However, adverse cardiovascular event rates in the first year after coronary artery bypass grafting (CABG) still exceed 10%. Graft failure, which is predominantly mediated by platelet aggregation, has been identified as a major contributing factor in this context. Therefore, intensified platelet inhibition is likely to be beneficial. Ticagrelor, an oral, reversibly binding and direct-acting P2Y12 receptor antagonist, provides a rapid, competent, and consistent platelet inhibition and has shown beneficial results compared with clopidogrel in the subset of patients undergoing bypass surgery in a large previous trial.


OBJECTIVE
Ticagrelor is superior to ASA for the prevention of major cardiovascular events within 1 year after CABG.


METHODS
The TiCAB trial (NCT01755520) is a multicenter, phase III, double-blind, double-dummy, randomized trial comparing ticagrelor with ASA for the prevention of major cardiovascular events within 12 months after CABG. Patients undergoing CABG will be randomized in a 1:1 fashion to either ticagrelor 90 mg twice daily or ASA 100 mg once daily. The study medication will be started within 24 hours after surgery and maintained for 12 months. The primary end point is the composite of cardiovascular death, myocardial infarction, stroke, and repeat revascularization at 12 months after CABG. The sample size is based on an expected event rate of 13% of the primary end point within the first 12 months after randomization in the control group, a 2-sided α level of .0492 (to preserve the overall significance level of .05 after planned interim analysis), a power of 0.80%, 2-sided testing, and an expected relative risk of 0.775 in the active group compared with the control group and a dropout rate of 2%. According to power calculations based on a superiority design for ticagrelor, it is estimated that 3,850 patients should be enrolled.


CONCLUSIONS
There is clinical equipoise on the issue of optimal platelet inhibition after CABG. The TiCAB trial will provide a pivotal comparison of the efficacy and safety of ticagrelor compared with ASA after CABG.
German Heart Center Munich, Technische Universität München, Munich, Germany; DZHK (German Center for Cardiovascular Research), and partner site Munich Heart Alliance, Munich, Germany. Electronic address: dewaha@dhm.mhn.de.
Antoinette
A
de Waha
Department of Cardiac Surgery, Vienna General Hospital, Medical University of Vienna, Vienna, Austria.
Sigrid
S
Sandner
German Heart Center Munich, Technische Universität München, Munich, Germany; DZHK (German Center for Cardiovascular Research), and partner site Munich Heart Alliance, Munich, Germany.
Moritz
M
von Scheidt
Department of Cardiovascular Surgery, Justus-Liebig University Gießen, Germany.
Andreas
A
Boening
German Heart Center Munich, Technische Universität München, Munich, Germany; DZHK (German Center for Cardiovascular Research), and partner site Munich Heart Alliance, Munich, Germany.
Katharina
K
Koch-Buettner
Department of Cardiac Surgery, Klinikum Links der Weser, Bremen, Germany.
Dieter
D
Hammel
Department of Cardiology and Angiology, Klinikum Links der Weser, Bremen, Germany.
Rainer
R
Hambrecht
Department of Thoracic and Cardiovascular Surgery, Georg-August-University Goettingen, Goettingen, Germany.
Bernhard C
BC
Danner
Department of Thoracic and Cardiovascular Surgery, Georg-August-University Goettingen, Goettingen, Germany.
Friedrich A
FA
Schöndube
Department of Cardiovascular Surgery, Justus-Liebig University Gießen, Germany.
Gerold
G
Goerlach
Department of Cardiac Surgery, Paracelsus Medical University, Klinikum Nürnberg, Germany.
Theodor
T
Fischlein
Department of Cardiac Surgery, Asklepios Klinik St. Georg/Cardioclinic Harburg, Hamburg, Germany.
Michael
M
Schmoeckel
Department of Cardiac Surgery, Asklepios Klinik St. Georg/Cardioclinic Harburg, Hamburg, Germany.
Martin
M
Oberhoffer
Institute of Physiology, Justus-Liebig University, Giessen, Germany.
Rainer
R
Schulz
Department of Cardiac Surgery, Kerckhoff Heart and Thorax Center, Bad Nauheim, Germany.
Thomas
T
Walther
Department of Cardiac Surgery, Kerckhoff Heart and Thorax Center, Bad Nauheim, Germany.
Tibor
T
Ziegelhöffer
Department of Cardiothoracic and Vascular Surgery, German Heart Institute Berlin, Germany.
Christoph
C
Knosalla
Department of Cardiothoracic and Vascular Surgery, German Heart Institute Berlin, Germany; DZHK (German Center for Cardiovascular research)-partner side Berlin.
Felix
F
Schönrath
Department of Cardiovascular Surgery, Heart Center Freiburg University, Freiburg, Germany.
Friedhelm
F
Beyersdorf
Department of Cardiovascular Surgery, Heart Center Freiburg University, Freiburg, Germany.
Matthias
M
Siepe
Department of Cardiovascular Surgery, University Hospital Schleswig-Holstein, Kiel, Germany.
Tim
T
Attmann
Department of Cardiac Surgery, Heart Center Leipzig, University of Leipzig, Leipzig, Germany.
Martin
M
Misfeld
Department of Cardiac Surgery, Heart Center Leipzig, University of Leipzig, Leipzig, Germany.
Friedrich-Wilhelm
FW
Mohr
Department of Cardiac and Thoracic Vascular Surgery, University of Lübeck, Lübeck, Germany.
Hans-Hinrich
HH
Sievers
Medical Clinic II, Cardiology, Angiology and Intensive Care Medicine, University Hospital Schleswig-Holstein, Campus Lübeck, Lübeck, Germany.
Alexander
A
Joost
Medical Clinic II, Cardiology, Angiology and Intensive Care Medicine, University Hospital Schleswig-Holstein, Campus Lübeck, Lübeck, Germany.
Leon M
LM
Putman
Department of Cardiac Surgery, Vienna General Hospital, Medical University of Vienna, Vienna, Austria.
Günther
G
Laufer
Department of Cardiology, Kerckhoff Heart and Thorax Center, Germany Justus Liebig University of Giessen, Department of Internal Medicine I, Gießen, Germany.
Christian
C
Hamm
Department of Cardiology, Heart Center Ludwigshafen, Ludwigshafen am Rhein, Germany.
Uwe
U
Zeymer
German Heart Center Munich, Technische Universität München, Munich, Germany; DZHK (German Center for Cardiovascular Research), and partner site Munich Heart Alliance, Munich, Germany.
Adnan
A
Kastrati
Klinik für Innere Medizin, Schön Klinik Neustadt, Neustadt i.H., Germany.
Peter W
PW
Radke
Department of Cardiovascular Surgery, German Heart Center Munich, Germany.
Rüdiger
R
Lange
Department of Cardiovascular Surgery, Heart Center Freiburg University, Freiburg, Germany.
Jochen
J
Cremer
German Heart Center Munich, Technische Universität München, Munich, Germany; DZHK (German Center for Cardiovascular Research), and partner site Munich Heart Alliance, Munich, Germany.
Heribert
H
Schunkert
D000241:Adenosine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000368:Aged; D001241:Aspirin / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000401:mortality; D001026:Coronary Artery Bypass / Q000379:methods*; D003324:Coronary Artery Disease / Q000628:therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology; D009204:Myocardial Revascularization / Q000706:statistics & numerical data; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D058921:Purinergic P2Y Receptor Antagonists / Q000627:therapeutic use*; D020521:Stroke / Q000453:epidemiology; D000077486:Ticagrelor; D016896:Treatment Outcome
D010975:Platelet Aggregation Inhibitors; D058921:Purinergic P2Y Receptor Antagonists; D000077486:Ticagrelor; D000241:Adenosine; D001241:Aspirin