Clinical Research
Angiographic Outcomes in the PLATO Trial (Platelet Inhibition and Patient Outcomes)

https://doi.org/10.1016/j.jcin.2013.03.014Get rights and content
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Objectives

The PLATO (Platelet Inhibition and Patient Outcomes) angiographic substudy sought to compare the efficacy of ticagrelor versus clopidogrel with respect to angiographic outcomes before and after PCI in the setting of acute coronary syndrome.

Background

Greater platelet inhibition has been associated with improved angiographic outcomes before and after percutaneous coronary intervention (PCI). Therefore, it was hypothesized that treatment with ticagrelor, which achieves more rapid, higher, and more consistent platelet inhibition, would be associated with improved angiographic outcomes when compared with those of clopidogrel treatment.

Methods

The angiographic cohort consists of 2,616 patients drawn from the 18,624-patient PLATO trial. Clopidogrel naïve or pre-treated patients were randomized to 180 mg of ticagrelor or 300 mg of clopidogrel (75 mg for clopidogrel pre-treated patients). PCI patients were administered, as per treatment group: 1) an additional 90 mg of ticagrelor if >24 h following the initial loading dose; or 2) an optional further 300 mg of clopidogrel or placebo (total 600 mg) prior to PCI. The substudy primary endpoint was the incidence of post-PCI TIMI (Thrombolysis In Myocardial Infarction) myocardial perfusion grade 3 (TMPG 3) among patients who received a study drug prior to PCI.

Results

In total, 21.3% of patients were pretreated with clopidogrel prior to randomization. There was a short time interval between randomization and PCI (median: 0.68 [interquartile range (IQR): 0.30 to 2.21] h) among all patients. Post-PCI TMPG 3 was similar between the ticagrelor and clopidogrel groups (47.1% vs. 46.9%; p = 0.96). Likewise, the following pre-PCI outcomes were similar in the ticagrelor and clopidogrel groups, respectively: TMPG 3 (30.5% vs. 31.2%), TIMI flow grade 3 (37.1% vs. 39.3%), corrected TIMI frame count (median: 100 vs. 71 frames), TIMI thrombus grade 0 (24.1% vs. 27.6%), minimum lumen diameter (median: 0.3 [IQR: 0.0 to 0.6] vs. 0.3 [IQR: 0.0 to 0.6] mm) and percentage of diameter stenosis (median: 89 [IQR: 78 to 100] vs. 89 [IQR: 77 to 100]).

Conclusions

Neither coronary flow nor myocardial perfusion, evaluated on coronary angiograms performed before or following PCI procedures within a few hours after the start of oral antiplatelet treatment in the setting of acute coronary syndromes, demonstrated a difference with ticagrelor versus clopidogrel. (A Comparison of Ticagrelor [AZD6140] and Clopidogrel in Patients With Acute Coronary Syndrome [PLATO]; NCT00391872)

Key Words

clopidogrel
corrected TIMI frame count
Thrombolysis in Myocardial Infarction
ticagrelor
TIMI myocardial perfusion grade

Abbreviations and Acronyms

ACS
acute coronary syndromes
CTFC
corrected TIMI frame count
IQR
interquartile range
MI
myocardial infarction
NSTE
non–ST-segment elevation
PCI
percutaneous coronary intervention
PD
pharmacodynamic
STEMI
ST-segment elevation myocardial infarction
TIMI
Thrombolysis In Myocardial Infarction
TMPG
TIMI myocardial perfusion grade

Cited by (0)

The PLATO trial was funded by AstraZeneca. Dr. Kunadian has received research support and honoraria from Eli Lilly/Daiichi Sankyo, Abbott Vascular, and The Medicines Company. Dr. James has received institutional research grant and/or honoraria from AstraZeneca, Eli Lilly, Merck & Co., Inc., Bristol-Myers Squibband The Medicines Company; and served as an advisory board member for AstraZeneca, Eli Lilly, and Merck & Co., Inc. Dr. Storey has received research grants from AstraZeneca, Eli Lilly/Daiichi Sankyo, and Merck & Co. Inc.; research support from Accumetrics; honoraria from AstraZeneca, Eli Lilly/Daiichi Sankyo, Merck & Co. Inc., Novartis, The Medicines Company, Iroko, sanofi-aventis/Regeneron, Bristol-Myers Squibb, Accumetrics, Medscape, and Eisai; and consultancy fees from AstraZeneca, Merck & Co. Inc., Novartis, Accumetrics, and Eisai. Dr. Steg has received research grants from New York University School of Medicine, sanofi-aventis, and Servier; has received consulting fees/honoraria from Ablynx, Amarin, Amgen, Astellas, AstraZeneca, Bayer HealthCare, Boehringer-Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Eisai, GlaxoSmithKline, Lilly, Medtronic, Merck & Co., Inc., Merck, Sharp, and Dohme, Novartis, Otsuka, Pfizer, Inc., Roche Diagnostics, sanofi-aventis, Servier, The Medicines Company, and Vivus; and has equity ownership in Aterovax. Dr. Katus has received consulting and lecture fees from AstraZeneca. Drs. Emanuelsson, Horrow, and Maya are equity-owning employees of AstraZeneca. Dr. Wallentin has received research grants from AstraZeneca, Merck & Co., Inc., Schering-Plough, Boehringer-Ingelheim, Bristol-Myers Squibb, Pfizer, Inc., and GlaxoSmithKline; consulting fees from Merck & Co., Inc., Schering-Plough, Regado Biosciences, Evolva, Portola Pharmaceuticals, C.S.L. Behring, Athera Biotechnologies, Boehringer-Ingelheim, AstraZeneca, GlaxoSmithKline, Bristol-Myers Squibb, and Pfizer, Inc.; lecture fees from AstraZeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, Pfizer, Inc., GlaxoSmithKline, Merck & Co., Inc., and Schering-Plough; honoraria from Boehringer-Ingelheim, AstraZeneca, Bristol-Myers Squibb, Pfizer, Inc., GlaxoSmithKline, Merck & Co., Inc., and Schering-Plough; and travel support from Bristol-Myers Squibb and Pfizer, Inc. Dr. Harrington has received consulting fees from Bristol-Myers Squibb, sanofi-aventis, Portola Pharmaceuticals, Schering-Plough, and AstraZeneca; lecture fees from Schering-Plough, Bristol-Myers Squibb, sanofi-aventis, and Eli Lilly; grant support from Merck & Co., Inc., Millennium Pharmaceuticals, Schering-Plough, The Medicines Company, Portola Pharmaceuticals, Regado Biosciences, AstraZeneca, and Bristol-Myers Squibb; has served on the advisory boards of WebMD, Gilead Sciences, Merck & Co., Inc., Regado Biosciences, and Johnson & Johnson. Dr. Gibson has received research grant support from AstraZeneca, Eli Lilly, and sanofi-aventis; and consulting fees and honoraria from Eli Lilly and sanofi-aventis. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.