See also:

PLATO study, 2009
[NCT00391872]	download pdf: ticagrelor | antithrombotics for acute coronary syndrome

Treatments

Studied treatment	ticagrelor 90mg twice daily oral loading dose of ticagrelor 180 mg
Control treatment	clopidogrel 75mg once daily oral loading dose of clopidogrel 300 mg
Concomittant treatment	All patients received acetylsalicylic acid (aspirin) at a dose of 75 to 100 mg daily unless they could not tolerate the drug.
Remarks	Patients undergoing PCI after randomization received, in a blind fashion, an additional dose of their study drug at the time of PCI

Patients

Patients	patients with an acute coronary syndrome, with or without ST-segment elevation (onset of symptoms within the previous 24h).
Inclusion criteria	acute coronary syndrome, with or without ST-segment elevation, with an onset of symptoms during the previous 24 hours;
Exclusion criteria	contraindication to clopidogrel; fibrinolytic therapy within 24 hours before; need for oral anticoagulation therapy; increased risk of bradycardia; concomitant therapy with a strong cytochrome P-450 3A inhibitor or inducer
Baseline characteristics	Age (mean), years 62y (median)  female (%) 28.3%  BMI (mdian) 27 (13-70)  history of MI (%) 20.5%  Positive troponin I 85.7%  ST-elevation MI 37.8%  Non–ST-elevation MI 42.7%

Method and design

Randomized effectives	9333 / 9291 (studied vs. control)
Design	Parallel groups
Blinding	double blind
Follow-up duration	1 y
Number of centre	862
Geographic area	43 countries
Hypothesis	Superiority
Primary endpoint	Cv death, MI, stroke
Withdrawals (T1/T0)	23.5% / 21.5%

Results

Endpoints and data reported in the trial's publication(s)

Endpoint	Events (%)		Relative Risk	95% CI
	Studied treat.	Control treat.
vascular death, MI, stroke	864 / 9333 (9,3%)	1014 / 9291 (10,9%)	0,85	[0,78;0,92]
Death from any cause, MI, or stroke	901 / 9333 (9,7%)	1065 / 9291 (11,5%)	0,84	[0,77;0,92]
vascular Death, MI, stroke, recurrent ischemia,TIA, other arterial thrombotic event	1290 / 9333 (13,8%)	1456 / 9291 (15,7%)	0,88	[0,82;0,95]
MI	504 / 9333 (5,4%)	593 / 9291 (6,4%)	0,85	[0,75;0,95]
Death from vascular causes	353 / 9333 (3,8%)	442 / 9291 (4,8%)	0,80	[0,69;0,91]
Stroke	125 / 9333 (1,3%)	106 / 9291 (1,1%)	1,17	[0,91;1,52]
Ischemic stroke	96 / 9333 (1,0%)	91 / 9291 (1,0%)	1,05	[0,79;1,40]
Hemorrhagic stroke	23 / 9333 (0,2%)	13 / 9291 (0,1%)	1,76	[0,89;3,47]
Unknown stroke	10 / 9333 (0,1%)	2 / 9291 (0,0%)	4,98	[1,09;22,71]
Death from any cause	399 / 9333 (4,3%)	506 / 9291 (5,4%)	0,78	[0,69;0,89]
Death from causes other than vascular causes	46 / 9333 (0,5%)	64 / 9291 (0,7%)	0,72	[0,49;1,04]
Severe recurrent ischemia	302 / 9333 (3,2%)	345 / 9291 (3,7%)	0,87	[0,75;1,01]
Recurrent ischemia	500 / 9333 (5,4%)	536 / 9291 (5,8%)	0,93	[0,82;1,05]
TIA	18 / 9333 (0,2%)	23 / 9291 (0,2%)	0,78	[0,42;1,44]
Other arterial thrombotic event	19 / 9333 (0,2%)	31 / 9291 (0,3%)	0,61	[0,34;1,08]
Death from vascular causes, MI, stroke Invasive treatment planned	569 / 9333 (6,1%)	668 / 9291 (7,2%)	0,85	[0,76;0,94]
Death from vascular causes, MI, stroke days 1–30	443 / 9333 (4,7%)	502 / 9291 (5,4%)	0,88	[0,78;0,99]
Death from vascular causes, MI, stroke, days 31–360	413 / 9333 (4,4%)	510 / 9291 (5,5%)	0,81	[0,71;0,91]
Definite Stent thrombosis	71 / 9333 (0,8%)	106 / 9291 (1,1%)	0,67	[0,49;0,90]
Probable or definite Stent thrombosis	118 / 9333 (1,3%)	158 / 9291 (1,7%)	0,74	[0,59;0,94]
Possible, probable, or definite Stent thrombosis	155 / 9333 (1,7%)	202 / 9291 (2,2%)	0,76	[0,62;0,94]
Major bleeding study criteria	961 / 9333 (10,3%)	929 / 9291 (10,0%)	1,03	[0,95;1,12]
TIMI Major bleeding	657 / 9333 (7,0%)	638 / 9291 (6,9%)	1,03	[0,92;1,14]
Bleeding requiring red-cell transfusion	818 / 9333 (8,8%)	809 / 9291 (8,7%)	1,01	[0,92;1,10]
Life-threatening or fatal bleeding	491 / 9333 (5,3%)	480 / 9291 (5,2%)	1,02	[0,90;1,15]
Fatal bleeding	20 / 9333 (0,2%)	23 / 9291 (0,2%)	0,87	[0,48;1,58]
Nonintracranial fatal bleeding	9 / 9333 (0,1%)	21 / 9291 (0,2%)	0,43	[0,20;0,93]
Intracranial bleeding	26 / 9333 (0,3%)	14 / 9291 (0,2%)	1,85	[0,97;3,54]
Fatal Intracranial bleeding	11 / 9333 (0,1%)	1 / 9291 (0,0%)	10,95	[1,41;84,80]
Nonfatal Intracranial bleeding	15 / 9333 (0,2%)	13 / 9291 (0,1%)	1,15	[0,55;2,41]
Non–CABG-related major bleeding	362 / 9333 (3,9%)	306 / 9291 (3,3%)	1,18	[1,01;1,37]
TIMI Non–CABG-related major bleeding	221 / 9333 (2,4%)	177 / 9291 (1,9%)	1,24	[1,02;1,51]
CABG-related major bleeding	619 / 9333 (6,6%)	654 / 9291 (7,0%)	0,94	[0,85;1,05]
TIMI CABG-related major bleeding	446 / 9333 (4,8%)	476 / 9291 (5,1%)	0,93	[0,82;1,06]
Major or minor bleeding	1339 / 9333 (14,3%)	1215 / 9291 (13,1%)	1,10	[1,02;1,18]
TIMI Major or minor bleeding	946 / 9333 (10,1%)	906 / 9291 (9,8%)	1,04	[0,95;1,13]
Any Dyspnea	1270 / 9333 (13,6%)	721 / 9291 (7,8%)	1,75	[1,61;1,91]
Dyspnea Requiring discontinuation of study treatment	79 / 9333 (0,8%)	13 / 9291 (0,1%)	6,05	[3,37;10,87]

Endpoints used by the meta-analysis and data retained for this trial

Endpoint Studied treat.
n/N Control treat.
n/N Graph RR [95% CI]

all cause death, MI, stroke

901 / 9333
1065 / 9291
0,84 [0,77;0,92]

cardiovascular events

864 / 9333
1014 / 9291
0,85 [0,78;0,92]

ischemic stroke

96 / 9333
91 / 9291
1,05 [0,79;1,40]

Vascular death

353 / 9333
442 / 9291
0,80 [0,69;0,91]

Major bleeding

657 / 9333
638 / 9291
1,03 [0,92;1,14]

stroke (fatal and non fatal)

125 / 9333
106 / 9291
1,17 [0,91;1,52]

All cause death

399 / 9333
506 / 9291
0,78 [0,69;0,89]

Non vascular death

46 / 9333
64 / 9291
0,72 [0,49;1,04]

myocardial infarction (fatal and non fatal)

504 / 9333
593 / 9291
0,85 [0,75;0,95]

fatal bleeding

20 / 9333
23 / 9291
0,87 [0,48;1,58]

Bleeding

946 / 9333
906 / 9291
1,04 [0,95;1,13] 0 2 1.0

Relative risks
Endpoint	Events (%)		Relative Risk	95% CI	Endpoint definition in the trial	Ref
	Studied treat.	Control treat.
all cause death, MI, stroke	901 / 9333 (9,7%)	1065 / 9291 (11,5%)	0,84	[0,77;0,92]
cardiovascular events	864 / 9333 (9,3%)	1014 / 9291 (10,9%)	0,85	[0,78;0,92]	vascular death, MI, stroke
ischemic stroke	96 / 9333 (1,0%)	91 / 9291 (1,0%)	1,05	[0,79;1,40]
Vascular death	353 / 9333 (3,8%)	442 / 9291 (4,8%)	0,80	[0,69;0,91]
Major bleeding	657 / 9333 (7,0%)	638 / 9291 (6,9%)	1,03	[0,92;1,14]	TIMI criteria
stroke (fatal and non fatal)	125 / 9333 (1,3%)	106 / 9291 (1,1%)	1,17	[0,91;1,52]
fatal bleeding	20 / 9333 (0,2%)	23 / 9291 (0,2%)	0,87	[0,48;1,58]
Bleeding	946 / 9333 (10,1%)	906 / 9291 (9,8%)	1,04	[0,95;1,13]	TIMI criteria
Non vascular death	46 / 9333 (0,5%)	64 / 9291 (0,7%)	0,72	[0,49;1,04]
myocardial infarction (fatal and non fatal)	504 / 9333 (5,4%)	593 / 9291 (6,4%)	0,85	[0,75;0,95]
All cause death	399 / 9333 (4,3%)	506 / 9291 (5,4%)	0,78	[0,69;0,89]
The primary endpoint (if exists) appears in blod characters
Reference(s) used for data extraction:

Endpoint	studied treat.	control treat.	mean diff

Absolute risk reduction
Endpoint	Events rate		Absolute risk reduction (ARR)
	Studied treat.	Control treat.
all cause death, MI, stroke	9,65%	11,46%	-18,1‰
cardiovascular events	9,26%	10,91%	-16,6‰
ischemic stroke	1,03%	9,79‰	0,5‰
Vascular death	3,78%	4,76%	-9,8‰
Major bleeding	7,04%	6,87%	1,7‰
stroke (fatal and non fatal)	1,34%	1,14%	2,0‰
fatal bleeding	2,14‰	2,48‰	-0,3‰
Bleeding	10,14%	9,75%	3,8‰
Non vascular death	4,93‰	6,89‰	-2,0‰
myocardial infarction (fatal and non fatal)	5,40%	6,38%	-9,8‰
All cause death	4,28%	5,45%	-11,7‰

Meta-analysis of all similar trials:

antiplatelets drug in acute coronary syndrome for ACS (excluding AMI)

antiplatelets drug in acute coronary syndrome for all type of patients

antithrombotics in acute coronary syndrome for all type of patient

New P2Y12 Inhibitors in acute coronary syndrome for all type of patients

Reference(s)

Trials register #

NCT00391872

• James S, Akerblom A, Cannon CP, Emanuelsson H, Husted S, Katus H, Skene A, Steg PG, Storey RF, Harrington R, Becker R, Wallentin L. Comparison of ticagrelor, the first reversible oral P2Y(12) receptor antagonist, with clopidogrel in patients with acute coronary syndromes: Rationale, design, and baseline characteristics of the PLATelet inhibition and patient Outcomes (PLATO) trial.. Am Heart J 2009;157:599-605
  Pubmed | Hubmed | Fulltext
• Wallentin L, Becker RC, Budaj A, Cannon CP, Emanuelsson H, Held C, Horrow J, Husted S, James S, Katus H, Mahaffey KW, Scirica BM, Skene A, Steg PG, Storey RF, Harrington RA. Ticagrelor versus Clopidogrel in Patients with Acute Coronary Syndromes.. N Engl J Med 2009 Aug 30;: - 10.1056/NEJMoa0904327
  Pubmed | Hubmed | Fulltext
• Bellemain-Appaix A, Brieger D, Beygui F, Silvain J, Pena A, Cayla G, Barthélémy O, Collet JP, Montalescot G. New P2Y12 Inhibitors Versus Clopidogrel in Percutaneous Coronary Intervention A Meta-Analysis.. J Am Coll Cardiol 2010 Aug 18;: - 10.1016/j.jacc.2010.07.012
  Pubmed | Hubmed | Fulltext

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