Impact of glycoprotein IIb/IIIa inhibitors on the efficacy and safety of ticagrelor compared with clopidogrel in patients with acute coronary syndromes: Analysis from the Platelet Inhibition and Patient Outcomes (PLATO) Trial.
BACKGROUND
Ticagrelor reduced cardiovascular events compared with clopidogrel in PLATO without increasing overall major bleeding. We evaluated whether the use of glycoprotein IIb/IIIa inhibitor (GPI) impacts the relative efficacy and safety of ticagrelor compared with clopidogrel.


METHODS
PLATO randomized 18,624 subjects with acute coronary syndrome to ticagrelor versus clopidogrel. The primary efficacy end point was cardiovascular death/myocardial infarction/stroke, and the primary safety end point was major bleeding. The use of GPI was at the physician's discretion and open-label. We evaluated outcomes at 30 days stratified by GPI use in the subgroup of 9,983 patients who underwent percutaneous coronary intervention (PCI) within 72 hours.


RESULTS
A total of 4,020 (40%) received a GPI. Those receiving a GPI were more likely to be younger, be male, and undergo multivessel PCI. There was no interaction between treatment and GPI use for the primary efficacy and safety end points. Patients treated without GPI had a lower rate of definite stent thrombosis and higher rate of minor/major bleeding with ticagrelor compared with clopidogrel (P < .05), whereas there was no such difference with GPI (P interaction < .05).


CONCLUSIONS
In patients with acute coronary syndrome undergoing early PCI, the efficacy and safety of ticagrelor as compared with clopidogrel were not modified by GPI use according to the primary efficacy and safety end point of the trial, although there were indications of greater benefit on definite stent thrombosis and more major or minor bleeding with ticagrelor in patients without (vs with) GPI treatment.
Harvard Clinical Research Institute, Boston, MA; Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
Yuichi J
YJ
Shimada
Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, NY.
Sameer
S
Bansilal
Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
Stephen D
SD
Wiviott
Division of Cardiovascular Health and Disease, Heart, Lung and Vascular Institute, University of Cincinnati College of Medicine, Cincinnati, OH.
Richard C
RC
Becker
Department of Medicine, Stanford University, Stanford, CA.
Robert A
RA
Harrington
AstraZeneca Research and Development, Mölndal, Sweden.
Anders
A
Himmelmann
Duke Clinical Research Institute, Duke University, Medical Center, Durham, NC.
Benjamin
B
Neely
Medical Department, Hospital Unit West, Herning/Holstebro, Denmark.
Steen
S
Husted
Department of Medical Sciences, Cardiology, Uppsala University, Uppsala, Sweden; Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
Stefan K
SK
James
Medizinishe Klinik, Universitätsklinikum Heidelberg, Heidelberg, Germany.
Hugo A
HA
Katus
Duke Clinical Research Institute, Duke University, Medical Center, Durham, NC.
Renato D
RD
Lopes
INSERM-Unité 1148, Paris, France; Assistance Publique-Hôpitaux de Paris, Département Hospitalo-Universitaire FIRE, Hôpital Bichat, Paris, France; Université Paris-Diderot, Sorbonne-Paris Cité, Paris, France; NHLI Imperial College, ICMS, Royal Brompton Hospital, London, United Kingdom.
Ph Gabriel
PG
Steg
Department of Cardiovascular Science, University of Sheffield, Sheffield, United Kingdom.
Robert F
RF
Storey
Department of Medical Sciences, Cardiology, Uppsala University, Uppsala, Sweden; Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
Lars
L
Wallentin
Harvard Clinical Research Institute, Boston, MA; Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA. Electronic address: christopher.cannon@hcri.harvard.edu.
Christopher P
CP
Cannon
D000077284:Abciximab; D054058:Acute Coronary Syndrome / Q000628:therapy*; D000241:Adenosine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D001241:Aspirin / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000401:mortality; D000077144:Clopidogrel; D004359:Drug Therapy, Combination; D054855:Drug-Eluting Stents; D000077542:Eptifibatide; D005260:Female; D006083:Graft Occlusion, Vascular / Q000453:epidemiology; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology; D010455:Peptides / Q000627:therapeutic use; D062645:Percutaneous Coronary Intervention; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors*; D058921:Purinergic P2Y Receptor Antagonists / Q000627:therapeutic use*; D020521:Stroke / Q000453:epidemiology; D013927:Thrombosis / Q000453:epidemiology; D000077486:Ticagrelor; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000077466:Tirofiban; D014443:Tyrosine / Q000031:analogs & derivatives / Q000627:therapeutic use
D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D010455:Peptides; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D058921:Purinergic P2Y Receptor Antagonists; D014443:Tyrosine; D000077144:Clopidogrel; D000077466:Tirofiban; D000077486:Ticagrelor; D000241:Adenosine; D000077542:Eptifibatide; D013988:Ticlopidine; D001241:Aspirin; D000077284:Abciximab