Cardiovascular events in acute coronary syndrome patients with peripheral arterial disease treated with ticagrelor compared with clopidogrel: Data from the PLATO Trial.
OBJECTIVE
To determine the effect of ticagrelor compared to clopidogrel in patients with peripheral artery disease (PAD) and acute coronary syndromes (ACS).


RESULTS
PLATO (n = 18,624) was a multicentre, double-blind, randomized trial in ACS, that showed a 16% reduction in cardiovascular death (CV-death), myocardial infarction (MI) and stroke with ticagrelor compared with clopidogrel, without significant increase in overall major bleeding. We performed a post-hoc analysis of cardiovascular and bleeding outcomes in PLATO according to reported PAD status at baseline. At one year, CV death, MI or stroke occurred in 19.3% of patients with PAD (n = 1144) compared to 10.2% in patients without PAD (p < 0.001). The Kaplan-Meier one year event rate for the primary endpoint of CV death, MI or stroke in PAD patients treated with ticagrelor as compared with clopidogrel, was 18% vs 20.6% (HR: 0.85 95% CI 0.64-1.11; for PAD status by treatment interaction, p = 0.99) and for death from any cause 8.7% vs 11.9%, (HR: 0.74 95% CI 0.50-1.08; interaction p = 0.73). PLATO-defined major bleeding event rates at one year were 14.8% for ticagrelor compared to 17.9% for clopidogrel, (HR: 0.81 95% CI 0.59-1.10; interaction p = 0.09).


CONCLUSIONS
PAD patients have a high rate of ischaemic and bleeding events post ACS. The reduction of CV death, MI or stroke with ticagrelor compared with clopidogrel in PAD patients was consistent with the overall trial result although it did not reach statistical significance. Overall major bleeding was similar between the therapies.
Duke Clinical Research Institute, Durham, NC, USA manesh.patel@duke.edu.
Manesh R
MR
Patel
Duke Clinical Research Institute, Durham, NC, USA Division of Cardiovascular Health and Disease, Heart, Lung and Vascular Institute, Academic Health Center, University of Cincinnati, Cincinnati, OH, USA.
Richard C
RC
Becker
Duke Clinical Research Institute, Durham, NC, USA.
Daniel M
DM
Wojdyla
AstraZeneca R&D, Mölndal, Sweden.
Hakan
H
Emanuelsson
University of Colorado, School of Medicine Division of Cardiology and CPC Clinical Research, Aurora, CO, USA.
William R
WR
Hiatt
AstraZeneca Research and Development, Wilmington, DE, USA.
Jay
J
Horrow
Medical Department, Hospital Unit West, Herning, Denmark.
Steen
S
Husted
Department of Medicine, Division of Cardiology, Stanford University, CA, USA.
Kenneth W
KW
Mahaffey
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, UK.
P Gabriel
PG
Steg
Department of Cardiovascular Science, University of Sheffield, Sheffield, UK.
Robert F
RF
Storey
Department of Medical Sciences, Cardiology, and Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
Lars
L
Wallentin
Department of Medical Sciences, Cardiology, and Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
Stefan K
SK
James
D054058:Acute Coronary Syndrome / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D000241:Adenosine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000368:Aged; D000077144:Clopidogrel; D004311:Double-Blind Method; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000209:etiology / Q000401:mortality / Q000517:prevention & control*; D058729:Peripheral Arterial Disease / Q000150:complications* / Q000175:diagnosis / Q000401:mortality; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D016016:Proportional Hazards Models; D012307:Risk Factors; D020521:Stroke / Q000209:etiology / Q000401:mortality / Q000517:prevention & control*; D000077486:Ticagrelor; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome
D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D000077486:Ticagrelor; D000241:Adenosine; D013988:Ticlopidine
Peripheral artery disease; acute coronary syndrome; ticagrelor