GLOBAL LEADERS: A Clinical Study Comparing Two Forms of Anti-platelet Therapy After Stent Implantation

• Sponsor: ECRI bv (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01813435
• Collaborator: Biosensors International (Other), AstraZeneca (Industry), The Medicines Company (Industry)
• Enrollment: 15,991
• Locations: 130
• Arms: 2
• Actual Duration (Months): 57.8
• Patients Per Site: 123
• Patients Per Site Per Month: 2.1

Study Details

Study Description

Brief Summary

After a stent procedure, it is common practice to prescribe anti-platelet medication to prevent the blood from clotting. The main objective of this study is to determine if there is a better medication strategy to prevent blood from clotting and at the same time minimising the number of complications.

There are two medication strategies:

• Study group: Dual anti-platelet therapy (ticagrelor combined with aspirin) for 1 month, and then ticagrelor alone for another 23 months OR

• Control group: Standard treatment, being dual anti-platelet therapy (ticagrelor or clopidogrel combined with aspirin) for 12 months, and then aspirin alone indefinitely

Condition or Disease	Intervention/Treatment	Phase
Coronary Artery Disease (CAD)	Drug: Ticagrelor; Drug: Acetylsalicylic Acid; Drug: Clopidogrel	Phase 3

Detailed Description

The study objective is to determine in all-comers patients undergoing percutaneous coronary intervention (PCI) under standardised treatment (including the BioMatrix family of drug-eluting stents and bivalirudin), whether treatment with 1 month of ticagrelor and aspirin followed by 23 months of ticagrelor monotherapy is superior with respect to the composite of all-cause mortality or non-fatal new Q-wave myocardial infarction (MI) compared to treatment with 12 months of standard dual anti platelet therapy (DAPT) followed by aspirin monotherapy.

The study design is an investigator-initiated, prospective randomised, multi-centre, multi-national, open-label trial to be conducted in approximately 60-80 interventional cardiology centres in Europe, North America, South America and Asia-Pacific. Patients will be randomised at a 1:1 ratio to study or reference treatment strategy.

Randomisation will occur at the time of the index procedure prior to PCI. Subjects will be stratified according to centre and according to the clinical presentation (Stable Coronary Artery Disease (CAD) vs. Acute Coronary Syndrome (ACS)).

All patients will be followed for a period of 2 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 15991 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: GLOBAL LEADERS: A Clinical Study Comparing Two Forms of Anti-platelet Therapy After Stent Implantation
• Actual Study Start Date: Jul 1, 2013
• Actual Primary Completion Date: Nov 9, 2015
• Actual Study Completion Date: Apr 26, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Experimental treatment strategy All patients in the treatment group will receive acetylsalicylic acid (ASA) and ticagrelor for 1 month followed by 23 months of ticagrelor monotherapy. Dosage and frequency: Ticagrelor: 90 mg b.i.d. ASA: of 75mg qd (- ≤ 100 mg qd)	Drug: Ticagrelor; Comparison of 1 month of ticagrelor and aspirin followed by 23 months of ticagrelor monotherapy versus 12 months of standard dual anti platelet therapy (DAPT) followed by aspirin monotherapy.; Other Names: Brilique ; Drug: Acetylsalicylic Acid; Comparison of 1 month of ticagrelor and aspirin followed by 23 months of ticagrelor monotherapy versus 12 months of standard dual anti platelet therapy (DAPT) followed by aspirin monotherapy; Other Names: Aspirin B01AC06
Active Comparator: Reference treatment strategy Acute Coronary Syndrome (ACS) patients incl. unstable angina (UA) patients: ASA and Brilique(ticagrelor) for 12 months followed by 12 months of ASA monotherapy. Stable Coronary Artery Disease (CAD) patients: ASA and clopidogrel for 12 months followed by 12 months of ASA monotherapy. Dosage and frequency: Brilique(Ticagrelor): 90 mg b.i.d. ASA: of 75mg qd (- ≤ 100 mg qd) Clopidogrel: 75 mg qd	Drug: Ticagrelor; Comparison of 1 month of ticagrelor and aspirin followed by 23 months of ticagrelor monotherapy versus 12 months of standard dual anti platelet therapy (DAPT) followed by aspirin monotherapy.; Other Names: Brilique ; Drug: Acetylsalicylic Acid; Comparison of 1 month of ticagrelor and aspirin followed by 23 months of ticagrelor monotherapy versus 12 months of standard dual anti platelet therapy (DAPT) followed by aspirin monotherapy; Other Names: Aspirin B01AC06 ; Drug: Clopidogrel; Active Comparator: Reference treatment strategy Acute Coronary Syndrome (ACS) patients incl. unstable angina (UA) patients: ASA and Brilique(ticagrelor) for 12 months followed by 12 months of ASA monotherapy. Stable Coronary Artery Disease (CAD) patients: ASA and clopidogrel for 12 months followed by 12 months of ASA monotherapy; Other Names: Plavix B01AC04

Outcome Measures

Primary Outcome Measures

1. Number of Participants With a Composite of All-cause Mortality or Non-fatal New Q-wave Myocardial Infarction (MI) [2 year]

   Number of Participants with a composite of all-cause mortality or non-fatal new Q-wave MI up to 2 years post randomisation.

Secondary Outcome Measures

1. Number of Participants With All-cause Mortality [2-year]

2. Number of Participants With Myocardial Infarction [2 year]

3. Number of Participants With New Q-wave Myocardial Infarction [2-year]

4. Number of Participants With a Composite of All-cause Mortality, Stroke, or New Q-wave Myocardial Infarction [2-year]

   shown are the first event per event type for each patient only. Multiple events of the same type within the same patient are disregarded

5. Number of Participants With a Stroke [2 year]

6. Number of Participants With a Myocardial Revascularisation [2 year]

7. Number of Participants With a Definite Stent Thrombosis [2 year]

8. Number of Participants With a Bleeding Academic Research Consortium (BARC) 3 or 5 Bleeding [2 year]

   BARC definition. We only considered BARC 3 or 5 for this secondary safety endpoint. Type 3: Clinical, laboratory, and/or imaging evidence of bleeding with: Type 3a: Overt bleeding + Hb drop of 3 to < 5 g/dL (provided Hb drop is related to bleed) Any transfusion with overt bleeding Type 3b: Overt bleeding + Hb drop ≥5 g/dL (provided Hb drop is related to bleed) Cardiac tamponade Bleeding requiring surgical intervention (excluding dental/nasal/skin/haemorrhoid) Bleeding requiring intravenous vasoactive agents Type 3c: Intracranial haemorrhage (does not include microbleeds or haemorrhagic transformation, does include intraspinal) Subcategories confirmed by autopsy or imaging or lumbar puncture Intraocular bleed compromising vision. Type 5: Fatal bleeding Type 5a: • Probable fatal bleeding; no autopsy or imaging confirmation but clinically suspicious Type 5b: Definite fatal bleeding; overt bleeding or autopsy or imaging confirmation

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

-"All comer" patients

1. Age ≥18 years;

2. Presence of one or more coronary artery stenoses of 50% or more in a native coronary artery or in a saphenous venous or arterial bypass conduit suitable for coronary stent implantation. The vessel should have a reference vessel diameter of at least 2.25 mm (no limitation on the number of treated lesions, vessels, or lesion length);

3. Able to provide informed consent and willing to participate in 2 year follow- up period.

Exclusion Criteria:

1. Known intolerance to aspirin, P2Y12 inhibitors, bivalirudin, stainless steel or biolimus;

2. Known intake of a strong CYP3A4 inhibitor (e.g., ketoconazole, clarithromycin, nefazodone, ritonavir, and atazanavir), as co-administration may lead to a substantial increase in exposure to ticagrelor;

3. Known moderate to severe hepatic impairment (alanine-aminotransferase ≥ 3 x ULN);

4. Planned surgery, including coronary artery bypass graft (CABG) as a staged procedure (hybrid) within 12 months of the index procedure, unless dual antiplatelet therapy is maintained throughout the peri-surgical period;

5. Need for chronic oral anti-coagulation therapy;

6. Active major bleeding or major surgery within the last 30 days;

7. Known history of intracranial haemorrhagic stroke or intra-cranial aneurysm;

8. Known stroke (any type) within the last 30 days;

9. Known pregnancy at time of randomisation;

10. Female who is breastfeeding at time of randomisation;

11. Currently participating in another trial and not yet at its primary endpoint.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research centre Brisbane, 6101	Brisbane		Australia
2	Research centre Melbourne, 6104	Melbourne		Australia
3	Research centre Melbourne, 6105	Melbourne		Australia
4	Research centre Graz, 4305	Graz		Austria
5	Rsearch centre Innsbruck, 4303	Innsbruck		Austria
6	Research centre Linz, 4304	Linz		Austria
7	Research centre Vienna, 4301	Vienna		Austria
8	Research centre Vienna, 4302	Vienna		Austria
9	Research centre Aalst, 3201	Aalst		Belgium
10	Research centre Aalst, 3206	Aalst		Belgium
11	Research centre Bonheiden, 3204	Bonheiden		Belgium
12	Research centre Charleroi, 3202	Charleroi		Belgium
13	Research centre Genk, 3205	Genk		Belgium
14	Research centre Hasselt, 3203	Hasselt		Belgium
15	Research centre Rio de Janeiro, 5503	Rio de Janeiro		Brazil
16	Research centre Rio de Janeiro, 5504	Rio de Janeiro		Brazil
17	Research centre Sao Paulo, 5501	Sao Paulo		Brazil
18	Research centre Sao Paulo, 5502	Sao Paulo		Brazil
19	Research centre Uberlândia, 5505	Uberlândia		Brazil
20	Research centre Burgas, 9902	Burgas		Bulgaria
21	Research centre Plovdiv, 9905	Plovdiv		Bulgaria
22	Research centre Sofia, 9901	Sofia		Bulgaria
23	Research centre Sofia, 9903	Sofia		Bulgaria
24	Research centre Sofia, 9904	Sofia		Bulgaria
25	Research centre Sofia, 9907	Sofia		Bulgaria
26	Research centre Sofia, 9908	Sofia		Bulgaria
27	Research centre Varna, 9906	Varna		Bulgaria
28	Research centre Newmarket, 1003	Newmarket		Canada
29	Research centre Quebec, 1001	Quebec		Canada
30	Research centre Copenhagen, 4501	Copenhagen		Denmark
31	Research centre Roskilde, 4503	Roskilde		Denmark
32	Research centre Aix en Provence, 3311	Aix en Provence		France
33	Research centre Caen, 3308	Caen		France
34	Research centre Caen, 3309	Caen		France
35	Research centre Clermont-Ferrand, 3303	Clermont-Ferrand		France
36	Research centre Dijon, 3313	Dijon		France
37	Research centre Grenoble, 3312	Grenoble Cedex		France
38	Research centre Lyon, 3316	Lyon		France
39	Research centre Nancy, 3314	Nancy		France
40	Research centre Paris, 3301	Paris		France
41	Research centre Paris, 3305	Paris		France
42	Research centre Rouen, 3307	Rouen		France
43	Research centre Saint Etienne, 3310	Saint Etienne		France
44	Research centre Toulouse, 3302	Toulouse		France
45	Research centre Bad Krozingen, 4904	Bad Krozingen		Germany
46	Research centre Bad Nauheim, 4902	Bad Nauheim		Germany
47	Research centre Berlin, 4918	Berlin		Germany
48	Research centre Bonn, 4911	Bonn		Germany
49	Research centre Dresden, 4908	Dresden		Germany
50	Research centre Essen, 4903	Essen		Germany
51	Research centre Fulda, 4905	Fulda		Germany
52	Research centre Giessen 4901	Giessen		Germany
53	Research centre Göttingen, 4907	Göttingen		Germany
54	Research centre Landshut, 4909	Landshut		Germany
55	Research centre Lubeck, 4917	Lubeck		Germany
56	Research centre Mainz, 4910	Mainz		Germany
57	Research centre Mannheim, 4912	Mannheim		Germany
58	Research centre Mönchengladbach, 4915	Mönchengladbach		Germany
59	Research centre Neuss, 4916	Neuss		Germany
60	Research centre Tubingen, 4914	Tubingen		Germany
61	Research centre Villingen - Schwenningen, 4919	Villingen - Schwenningen		Germany
62	Research centre Balatonfüred, 3608	Balatonfüred		Hungary
63	Research centre Budapest, 3602	Budapest		Hungary
64	Research centre Budapest, 3603	Budapest		Hungary
65	Research centre Debrecen, 3607	Debrecen		Hungary
66	Research centre Gyula, 3606	Gyula		Hungary
67	Research centre Nyíregyháza, 3605	Nyíregyháza		Hungary
68	Research centre Pécs, 3604	Pécs		Hungary
69	Research centre szeged, 3601	Szeged		Hungary
70	Research centre Arezzo, 3902	Arezzo		Italy
71	Research centre Brescia, 3912	Brescia		Italy
72	Research centre Ferrara, 3905	Ferrara		Italy
73	Research centre Milano, 3901	Milano		Italy
74	Research centre Pavia, 3903	Pavia		Italy
75	Research centre Terni, 3909	Terni		Italy
76	Research centre Alkmaar, 3106	Alkmaar		Netherlands
77	OLVG Research centre Amsterdam, 3104	Amsterdam		Netherlands
78	UMCG Groningen, 3108	Groningen		Netherlands
79	Research centre Leeuwarden, 3102	Leeuwarden		Netherlands
80	Research centre Nieuwegein, 3107	Nieuwegein		Netherlands
81	Research centre Nijmegen, 3105	Nijmegen		Netherlands
82	EMC Rotterdam, 3101	Rotterdam		Netherlands
83	Maasstad Rotterdam, 3103	Rotterdam		Netherlands
84	Research centre Tilburg, 3109	Tilburg		Netherlands
85	Research centre Chrzanow, 4802	Chrzanow		Poland
86	Research centre Dabrowa Gornicza, 4801	Dabrowa Gornicza		Poland
87	Research centre Kedzierzyn-Kozle, 4805	Kedzierzyn-Kozle		Poland
88	Research centre Krakov, 4807	Krakov		Poland
89	Research centre Mielec, 4809	Mielec		Poland
90	Research centre Nysa, 4808	Nysa		Poland
91	Research centre Ustroń, 4803	Ustroń		Poland
92	Research centre Gaia, 3501	Gaia		Portugal
93	Research centre Lisbon, 3503	Lisbon		Portugal
94	Research centre Lisbon, 3504	Lisbon		Portugal
95	Research centre Lisbon, 3505	Lisbon		Portugal
96	Research centre Singapore, 6501	Singapore		Singapore
97	Research centre Singapore, 6502	Singapore		Singapore
98	Research centre Barcelona, 3401	Barcelona		Spain
99	Research centre Barcelona, 3403	Barcelona		Spain
100	Research centre Barcelona, 3405	Barcelona		Spain
101	Research centre Huelva, 3408	Huelva		Spain
102	Research centre Madrid 3410	Madrid		Spain
103	Research centre Madrid, 3402	Madrid		Spain
104	Research centre Madrid, 3407	Madrid		Spain
105	Research centre Madrid, 3409	Madrid		Spain
106	Research centre Vigo, 3404	Vigo		Spain
107	Research centre Bern, 4106	Bern		Switzerland
108	Research centre Bern, 4107	Bern		Switzerland
109	Research centre Geneva, 4101	Geneva		Switzerland
110	Research centre Lausanne, 4104	Lausanne		Switzerland
111	Research centre Liestal, 4108	Liestal		Switzerland
112	Research centre Lugano, 4105	Lugano		Switzerland
113	Research centre Belfast, 4420	Belfast		United Kingdom
114	Research Centre Belfast, 4423	Belfast		United Kingdom
115	Research centre Blackburn, 4404	Blackburn		United Kingdom
116	Research centre Blackpool, 4408	Blackpool		United Kingdom
117	Research centre Bournemouth, 4418	Bournemouth		United Kingdom
118	Research centre Brighton, 4405	Brighton		United Kingdom
119	Research centre Cambridge, 4417	Cambridge		United Kingdom
120	Research centre Cardiff, 4402	Cardiff		United Kingdom
121	Research centre Glasgow, 4407	Glasgow		United Kingdom
122	Research centre Leicester, 4421	Leicester		United Kingdom
123	Research centre Liverpool, 4001	Liverpool		United Kingdom
124	Research centre Manchester, 4403	Manchester		United Kingdom
125	Research centre Manchester, 4406	Manchester		United Kingdom
126	Research centre Newcastle, 4413	Newcastle		United Kingdom
127	Research centre Rhyl, 4414	Rhyl		United Kingdom
128	Research centre Southampton, 4415	Southampton		United Kingdom
129	Research centre Stevenage, 4412	Stevenage		United Kingdom
130	Research centre Wolverhampton, 4422	Wolverhampton		United Kingdom

Sponsors and Collaborators

• ECRI bv
• Biosensors International
• AstraZeneca
• The Medicines Company

Investigators

• Study Director: Ernest Spitzer, MD, European Cardiovascular Research Institute
• Principal Investigator: Stephan Windecker, Prof. MD, Inselspital, University Hospital Bern, Switzerland

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Pubmed Identifier 30166073

Publications

• Vranckx P, Valgimigli M, Jüni P, Hamm C, Steg PG, Heg D, van Es GA, McFadden EP, Onuma Y, van Meijeren C, Chichareon P, Benit E, Möllmann H, Janssens L, Ferrario M, Moschovitis A, Zurakowski A, Dominici M, Van Geuns RJ, Huber K, Slagboom T, Serruys PW, Windecker S; GLOBAL LEADERS Investigators. Ticagrelor plus aspirin for 1 month, followed by ticagrelor monotherapy for 23 months vs aspirin plus clopidogrel or ticagrelor for 12 months, followed by aspirin monotherapy for 12 months after implantation of a drug-eluting stent: a multicentre, open-label, randomised superiority trial. Lancet. 2018 Sep 15;392(10151):940-949. doi: 10.1016/S0140-6736(18)31858-0. Epub 2018 Aug 27.

• Responsible Party: ECRI bv
• ClinicalTrials.gov Identifier: NCT01813435
• Other Study ID Numbers: ECRI-12-001, 02EU11
• First Posted: Mar 19, 2013
• Last Update Posted: Mar 15, 2022
• Last Verified: Mar 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Keywords provided by ECRI bv: CAD; ACS; All comers; DAPT; PCI
• Additional relevant MeSH terms: Coronary Artery Disease; Aspirin; Clopidogrel; Ticagrelor

Study Results

Participant Flow

Pre-assignment Detail	12 participants of the experimental group withdrew consent or objected to use further use of data 11 participants of the reference group withdrew consent or objected to use further use of data

Arm/Group Title	Experimental Treatment Strategy	Reference Treatment Strategy
Arm/Group Description	All patients in the treatment group will receive acetylsalicylic acid (ASA) and ticagrelor for 1 month followed by 23 months of ticagrelor monotherapy. Dosage and frequency: Ticagrelor: 90 mg b.i.d. ASA: of 75mg qd (- ≤ 100 mg qd) Ticagrelor: Comparison of 1 month of ticagrelor and aspirin followed by 23 months of ticagrelor monotherapy versus 12 months of standard dual anti platelet therapy (DAPT) followed by aspirin monotherapy. Acetylsalicylic Acid: Comparison of 1 month of ticagrelor and aspirin followed by 23 months of ticagrelor monotherapy versus 12 months of standard dual anti platelet therapy (DAPT) followed by aspirin monotherapy	Acute Coronary Syndrome (ACS) patients incl. unstable angina (UA) patients: ASA and Brilique(ticagrelor) for 12 months followed by 12 months of ASA monotherapy. Stable Coronary Artery Disease (CAD) patients: ASA and clopidogrel for 12 months followed by 12 months of ASA monotherapy. Dosage and frequency: Brilique(Ticagrelor): 90 mg b.i.d. ASA: of 75mg qd (- ≤ 100 mg qd) Clopidogrel: 75 mg qd Ticagrelor: Comparison of 1 month of ticagrelor and aspirin followed by 23 months of ticagrelor monotherapy versus 12 months of standard dual anti platelet therapy (DAPT) followed by aspirin monotherapy. Acetylsalicylic Acid: Comparison of 1 month of ticagrelor and aspirin followed by 23 months of ticagrelor monotherapy versus 12 months of standard dual anti platelet therapy (DAPT) followed by aspirin monotherapy Clopidogrel: Active Comparator: Reference treatment strategy Acute Coronary Syndrome (ACS) patients incl. unstable angina (UA) patients: ASA and Brilique(ticagrelor) for
Period Title: Overall Study
STARTED	7980	7988
COMPLETED	5810	6981
NOT COMPLETED	2170	1007

Baseline Characteristics

Arm/Group Title	Experimental Treatment Strategy	Reference Treatment Strategy	Total
Arm/Group Description	All patients in the treatment group will receive acetylsalicylic acid (ASA) and ticagrelor for 1 month followed by 23 months of ticagrelor monotherapy. Dosage and frequency: Ticagrelor: 90 mg b.i.d. ASA: of 75mg qd (- ≤ 100 mg qd) Ticagrelor: Comparison of 1 month of ticagrelor and aspirin followed by 23 months of ticagrelor monotherapy versus 12 months of standard dual anti platelet therapy (DAPT) followed by aspirin monotherapy. Acetylsalicylic Acid: Comparison of 1 month of ticagrelor and aspirin followed by 23 months of ticagrelor monotherapy versus 12 months of standard dual anti platelet therapy (DAPT) followed by aspirin monotherapy	Acute Coronary Syndrome (ACS) patients incl. unstable angina (UA) patients: ASA and Brilique(ticagrelor) for 12 months followed by 12 months of ASA monotherapy. Stable Coronary Artery Disease (CAD) patients: ASA and clopidogrel for 12 months followed by 12 months of ASA monotherapy. Dosage and frequency: Brilique(Ticagrelor): 90 mg b.i.d. ASA: of 75mg qd (- ≤ 100 mg qd) Clopidogrel: 75 mg qd Ticagrelor: Comparison of 1 month of ticagrelor and aspirin followed by 23 months of ticagrelor monotherapy versus 12 months of standard dual anti platelet therapy (DAPT) followed by aspirin monotherapy. Acetylsalicylic Acid: Comparison of 1 month of ticagrelor and aspirin followed by 23 months of ticagrelor monotherapy versus 12 months of standard dual anti platelet therapy (DAPT) followed by aspirin monotherapy Clopidogrel: Active Comparator: Reference treatment strategy Acute Coronary Syndrome (ACS) patients incl. unstable angina (UA) patients: ASA and Brilique(ticagrelor) for	Total of all reporting groups
Overall Participants	7980	7988	15968
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	3949 49.5%	3928 49.2%	7877 49.3%
>=65 years	4031 50.5%	4060 50.8%	8091 50.7%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	64.5 (10.3)	64.6 (10.3)	64.6 (10.3)
Sex: Female, Male (Count of Participants)
Female	1865 23.4%	1849 23.1%	3714 23.3%
Male	6115 76.6%	6139 76.9%	12254 76.7%
Region of Enrollment (participants) [Number]
Singapore	71 0.9%	71 0.9%	142 0.9%
Hungary	264 3.3%	263 3.3%	527 3.3%
United Kingdom	854 10.7%	859 10.8%	1713 10.7%
Portugal	56 0.7%	57 0.7%	113 0.7%
Switzerland	352 4.4%	353 4.4%	705 4.4%
Spain	475 6%	476 6%	951 6%
Canada	84 1.1%	86 1.1%	170 1.1%
Austria	335 4.2%	337 4.2%	672 4.2%
Netherlands	579 7.3%	580 7.3%	1159 7.3%
Belgium	1094 13.7%	1091 13.7%	2185 13.7%
Brazil	126 1.6%	122 1.5%	248 1.6%
Denmark	66 0.8%	65 0.8%	131 0.8%
Poland	768 9.6%	764 9.6%	1532 9.6%
Italy	790 9.9%	788 9.9%	1578 9.9%
Australia	41 0.5%	42 0.5%	83 0.5%
Bulgaria	470 5.9%	473 5.9%	943 5.9%
France	426 5.3%	423 5.3%	849 5.3%
Germany	1129 14.1%	1138 14.2%	2267 14.2%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With a Composite of All-cause Mortality or Non-fatal New Q-wave Myocardial Infarction (MI)
Description	Number of Participants with a composite of all-cause mortality or non-fatal new Q-wave MI up to 2 years post randomisation.
Time Frame	2 year

Outcome Measure Data

Analysis Population Description

Shown are the first event per event type for each patient only. Multiple events of the same type within the same patient are disregarded. Data were censored 730 days after index percutaneous coronary intervention.

Arm/Group Title	Experimental Treatment Strategy	Reference Treatment Strategy
Arm/Group Description	All patients in the treatment group will receive acetylsalicylic acid (ASA) and ticagrelor for 1 month followed by 23 months of ticagrelor monotherapy. Dosage and frequency: Ticagrelor: 90 mg b.i.d. ASA: of 75mg qd (- ≤ 100 mg qd) Ticagrelor: Comparison of 1 month of ticagrelor and aspirin followed by 23 months of ticagrelor monotherapy versus 12 months of standard dual anti platelet therapy (DAPT) followed by aspirin monotherapy. Acetylsalicylic Acid: Comparison of 1 month of ticagrelor and aspirin followed by 23 months of ticagrelor monotherapy versus 12 months of standard dual anti platelet therapy (DAPT) followed by aspirin monotherapy	Acute Coronary Syndrome (ACS) patients incl. unstable angina (UA) patients: ASA and Brilique(ticagrelor) for 12 months followed by 12 months of ASA monotherapy. Stable Coronary Artery Disease (CAD) patients: ASA and clopidogrel for 12 months followed by 12 months of ASA monotherapy. Dosage and frequency: Brilique(Ticagrelor): 90 mg b.i.d. ASA: of 75mg qd (- ≤ 100 mg qd) Clopidogrel: 75 mg qd Ticagrelor: Comparison of 1 month of ticagrelor and aspirin followed by 23 months of ticagrelor monotherapy versus 12 months of standard dual anti platelet therapy (DAPT) followed by aspirin monotherapy. Acetylsalicylic Acid: Comparison of 1 month of ticagrelor and aspirin followed by 23 months of ticagrelor monotherapy versus 12 months of standard dual anti platelet therapy (DAPT) followed by aspirin monotherapy Clopidogrel: Active Comparator: Reference treatment strategy Acute Coronary Syndrome (ACS) patients incl. unstable angina (UA) patients: ASA and Brilique(ticagrelor) for
Measure Participants	7980	7988
Count of Participants [Participants]	304 3.8%	349 4.4%

2. Secondary Outcome

Title	Number of Participants With All-cause Mortality
Time Frame	2-year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Experimental Treatment Strategy	Reference Treatment Strategy
Arm/Group Description	All patients in the treatment group will receive acetylsalicylic acid (ASA) and ticagrelor for 1 month followed by 23 months of ticagrelor monotherapy. Dosage and frequency: Ticagrelor: 90 mg b.i.d. ASA: of 75mg qd (- ≤ 100 mg qd) Ticagrelor: Comparison of 1 month of ticagrelor and aspirin followed by 23 months of ticagrelor monotherapy versus 12 months of standard dual anti platelet therapy (DAPT) followed by aspirin monotherapy. Acetylsalicylic Acid: Comparison of 1 month of ticagrelor and aspirin followed by 23 months of ticagrelor monotherapy versus 12 months of standard dual anti platelet therapy (DAPT) followed by aspirin monotherapy	Acute Coronary Syndrome (ACS) patients incl. unstable angina (UA) patients: ASA and Brilique(ticagrelor) for 12 months followed by 12 months of ASA monotherapy. Stable Coronary Artery Disease (CAD) patients: ASA and clopidogrel for 12 months followed by 12 months of ASA monotherapy. Dosage and frequency: Brilique(Ticagrelor): 90 mg b.i.d. ASA: of 75mg qd (- ≤ 100 mg qd) Clopidogrel: 75 mg qd Ticagrelor: Comparison of 1 month of ticagrelor and aspirin followed by 23 months of ticagrelor monotherapy versus 12 months of standard dual anti platelet therapy (DAPT) followed by aspirin monotherapy. Acetylsalicylic Acid: Comparison of 1 month of ticagrelor and aspirin followed by 23 months of ticagrelor monotherapy versus 12 months of standard dual anti platelet therapy (DAPT) followed by aspirin monotherapy Clopidogrel: Active Comparator: Reference treatment strategy Acute Coronary Syndrome (ACS) patients incl. unstable angina (UA) patients: ASA and Brilique(ticagrelor) for
Measure Participants	7980	7988
Count of Participants [Participants]	224 2.8%	253 3.2%

3. Secondary Outcome

Title	Number of Participants With Myocardial Infarction
Time Frame	2 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Experimental Treatment Strategy	Reference Treatment Strategy
Arm/Group Description	All patients in the treatment group will receive acetylsalicylic acid (ASA) and ticagrelor for 1 month followed by 23 months of ticagrelor monotherapy. Dosage and frequency: Ticagrelor: 90 mg b.i.d. ASA: of 75mg qd (- ≤ 100 mg qd) Ticagrelor: Comparison of 1 month of ticagrelor and aspirin followed by 23 months of ticagrelor monotherapy versus 12 months of standard dual anti platelet therapy (DAPT) followed by aspirin monotherapy. Acetylsalicylic Acid: Comparison of 1 month of ticagrelor and aspirin followed by 23 months of ticagrelor monotherapy versus 12 months of standard dual anti platelet therapy (DAPT) followed by aspirin monotherapy	Acute Coronary Syndrome (ACS) patients incl. unstable angina (UA) patients: ASA and Brilique(ticagrelor) for 12 months followed by 12 months of ASA monotherapy. Stable Coronary Artery Disease (CAD) patients: ASA and clopidogrel for 12 months followed by 12 months of ASA monotherapy. Dosage and frequency: Brilique(Ticagrelor): 90 mg b.i.d. ASA: of 75mg qd (- ≤ 100 mg qd) Clopidogrel: 75 mg qd Ticagrelor: Comparison of 1 month of ticagrelor and aspirin followed by 23 months of ticagrelor monotherapy versus 12 months of standard dual anti platelet therapy (DAPT) followed by aspirin monotherapy. Acetylsalicylic Acid: Comparison of 1 month of ticagrelor and aspirin followed by 23 months of ticagrelor monotherapy versus 12 months of standard dual anti platelet therapy (DAPT) followed by aspirin monotherapy Clopidogrel: Active Comparator: Reference treatment strategy Acute Coronary Syndrome (ACS) patients incl. unstable angina (UA) patients: ASA and Brilique(ticagrelor) for
Measure Participants	7980	7988
Count of Participants [Participants]	248 3.1%	250 3.1%

4. Secondary Outcome

Title	Number of Participants With New Q-wave Myocardial Infarction
Time Frame	2-year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Experimental Treatment Strategy	Reference Treatment Strategy
Arm/Group Description	All patients in the treatment group will receive acetylsalicylic acid (ASA) and ticagrelor for 1 month followed by 23 months of ticagrelor monotherapy. Dosage and frequency: Ticagrelor: 90 mg b.i.d. ASA: of 75mg qd (- ≤ 100 mg qd) Ticagrelor: Comparison of 1 month of ticagrelor and aspirin followed by 23 months of ticagrelor monotherapy versus 12 months of standard dual anti platelet therapy (DAPT) followed by aspirin monotherapy. Acetylsalicylic Acid: Comparison of 1 month of ticagrelor and aspirin followed by 23 months of ticagrelor monotherapy versus 12 months of standard dual anti platelet therapy (DAPT) followed by aspirin monotherapy	Acute Coronary Syndrome (ACS) patients incl. unstable angina (UA) patients: ASA and Brilique(ticagrelor) for 12 months followed by 12 months of ASA monotherapy. Stable Coronary Artery Disease (CAD) patients: ASA and clopidogrel for 12 months followed by 12 months of ASA monotherapy. Dosage and frequency: Brilique(Ticagrelor): 90 mg b.i.d. ASA: of 75mg qd (- ≤ 100 mg qd) Clopidogrel: 75 mg qd Ticagrelor: Comparison of 1 month of ticagrelor and aspirin followed by 23 months of ticagrelor monotherapy versus 12 months of standard dual anti platelet therapy (DAPT) followed by aspirin monotherapy. Acetylsalicylic Acid: Comparison of 1 month of ticagrelor and aspirin followed by 23 months of ticagrelor monotherapy versus 12 months of standard dual anti platelet therapy (DAPT) followed by aspirin monotherapy Clopidogrel: Active Comparator: Reference treatment strategy Acute Coronary Syndrome (ACS) patients incl. unstable angina (UA) patients: ASA and Brilique(ticagrelor) for
Measure Participants	7980	7988
Count of Participants [Participants]	83 1%	103 1.3%

5. Secondary Outcome

Title	Number of Participants With a Composite of All-cause Mortality, Stroke, or New Q-wave Myocardial Infarction
Description	shown are the first event per event type for each patient only. Multiple events of the same type within the same patient are disregarded
Time Frame	2-year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Experimental Treatment Strategy	Reference Treatment Strategy
Arm/Group Description	All patients in the treatment group will receive acetylsalicylic acid (ASA) and ticagrelor for 1 month followed by 23 months of ticagrelor monotherapy. Dosage and frequency: Ticagrelor: 90 mg b.i.d. ASA: of 75mg qd (- ≤ 100 mg qd) Ticagrelor: Comparison of 1 month of ticagrelor and aspirin followed by 23 months of ticagrelor monotherapy versus 12 months of standard dual anti platelet therapy (DAPT) followed by aspirin monotherapy. Acetylsalicylic Acid: Comparison of 1 month of ticagrelor and aspirin followed by 23 months of ticagrelor monotherapy versus 12 months of standard dual anti platelet therapy (DAPT) followed by aspirin monotherapy	Acute Coronary Syndrome (ACS) patients incl. unstable angina (UA) patients: ASA and Brilique(ticagrelor) for 12 months followed by 12 months of ASA monotherapy. Stable Coronary Artery Disease (CAD) patients: ASA and clopidogrel for 12 months followed by 12 months of ASA monotherapy. Dosage and frequency: Brilique(Ticagrelor): 90 mg b.i.d. ASA: of 75mg qd (- ≤ 100 mg qd) Clopidogrel: 75 mg qd Ticagrelor: Comparison of 1 month of ticagrelor and aspirin followed by 23 months of ticagrelor monotherapy versus 12 months of standard dual anti platelet therapy (DAPT) followed by aspirin monotherapy. Acetylsalicylic Acid: Comparison of 1 month of ticagrelor and aspirin followed by 23 months of ticagrelor monotherapy versus 12 months of standard dual anti platelet therapy (DAPT) followed by aspirin monotherapy Clopidogrel: Active Comparator: Reference treatment strategy Acute Coronary Syndrome (ACS) patients incl. unstable angina (UA) patients: ASA and Brilique(ticagrelor) for
Measure Participants	7980	7988
Count of Participants [Participants]	362 4.5%	416 5.2%

6. Secondary Outcome

Title	Number of Participants With a Stroke
Time Frame	2 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Experimental Treatment Strategy	Reference Treatment Strategy
Arm/Group Description	All patients in the treatment group will receive acetylsalicylic acid (ASA) and ticagrelor for 1 month followed by 23 months of ticagrelor monotherapy. Dosage and frequency: Ticagrelor: 90 mg b.i.d. ASA: of 75mg qd (- ≤ 100 mg qd) Ticagrelor: Comparison of 1 month of ticagrelor and aspirin followed by 23 months of ticagrelor monotherapy versus 12 months of standard dual anti platelet therapy (DAPT) followed by aspirin monotherapy. Acetylsalicylic Acid: Comparison of 1 month of ticagrelor and aspirin followed by 23 months of ticagrelor monotherapy versus 12 months of standard dual anti platelet therapy (DAPT) followed by aspirin monotherapy	Acute Coronary Syndrome (ACS) patients incl. unstable angina (UA) patients: ASA and Brilique(ticagrelor) for 12 months followed by 12 months of ASA monotherapy. Stable Coronary Artery Disease (CAD) patients: ASA and clopidogrel for 12 months followed by 12 months of ASA monotherapy. Dosage and frequency: Brilique(Ticagrelor): 90 mg b.i.d. ASA: of 75mg qd (- ≤ 100 mg qd) Clopidogrel: 75 mg qd Ticagrelor: Comparison of 1 month of ticagrelor and aspirin followed by 23 months of ticagrelor monotherapy versus 12 months of standard dual anti platelet therapy (DAPT) followed by aspirin monotherapy. Acetylsalicylic Acid: Comparison of 1 month of ticagrelor and aspirin followed by 23 months of ticagrelor monotherapy versus 12 months of standard dual anti platelet therapy (DAPT) followed by aspirin monotherapy Clopidogrel: Active Comparator: Reference treatment strategy Acute Coronary Syndrome (ACS) patients incl. unstable angina (UA) patients: ASA and Brilique(ticagrelor) for
Measure Participants	7980	7988
Count of Participants [Participants]	80 1%	82 1%

7. Secondary Outcome

Title	Number of Participants With a Myocardial Revascularisation
Time Frame	2 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Experimental Treatment Strategy	Reference Treatment Strategy
Arm/Group Description	All patients in the treatment group will receive acetylsalicylic acid (ASA) and ticagrelor for 1 month followed by 23 months of ticagrelor monotherapy. Dosage and frequency: Ticagrelor: 90 mg b.i.d. ASA: of 75mg qd (- ≤ 100 mg qd) Ticagrelor: Comparison of 1 month of ticagrelor and aspirin followed by 23 months of ticagrelor monotherapy versus 12 months of standard dual anti platelet therapy (DAPT) followed by aspirin monotherapy. Acetylsalicylic Acid: Comparison of 1 month of ticagrelor and aspirin followed by 23 months of ticagrelor monotherapy versus 12 months of standard dual anti platelet therapy (DAPT) followed by aspirin monotherapy	Acute Coronary Syndrome (ACS) patients incl. unstable angina (UA) patients: ASA and Brilique(ticagrelor) for 12 months followed by 12 months of ASA monotherapy. Stable Coronary Artery Disease (CAD) patients: ASA and clopidogrel for 12 months followed by 12 months of ASA monotherapy. Dosage and frequency: Brilique(Ticagrelor): 90 mg b.i.d. ASA: of 75mg qd (- ≤ 100 mg qd) Clopidogrel: 75 mg qd Ticagrelor: Comparison of 1 month of ticagrelor and aspirin followed by 23 months of ticagrelor monotherapy versus 12 months of standard dual anti platelet therapy (DAPT) followed by aspirin monotherapy. Acetylsalicylic Acid: Comparison of 1 month of ticagrelor and aspirin followed by 23 months of ticagrelor monotherapy versus 12 months of standard dual anti platelet therapy (DAPT) followed by aspirin monotherapy Clopidogrel: Active Comparator: Reference treatment strategy Acute Coronary Syndrome (ACS) patients incl. unstable angina (UA) patients: ASA and Brilique(ticagrelor) for
Measure Participants	7980	7988
Count of Participants [Participants]	739 9.3%	793 9.9%

8. Secondary Outcome

Title	Number of Participants With a Definite Stent Thrombosis
Time Frame	2 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Experimental Treatment Strategy	Reference Treatment Strategy
Arm/Group Description	All patients in the treatment group will receive acetylsalicylic acid (ASA) and ticagrelor for 1 month followed by 23 months of ticagrelor monotherapy. Dosage and frequency: Ticagrelor: 90 mg b.i.d. ASA: of 75mg qd (- ≤ 100 mg qd) Ticagrelor: Comparison of 1 month of ticagrelor and aspirin followed by 23 months of ticagrelor monotherapy versus 12 months of standard dual anti platelet therapy (DAPT) followed by aspirin monotherapy. Acetylsalicylic Acid: Comparison of 1 month of ticagrelor and aspirin followed by 23 months of ticagrelor monotherapy versus 12 months of standard dual anti platelet therapy (DAPT) followed by aspirin monotherapy	Acute Coronary Syndrome (ACS) patients incl. unstable angina (UA) patients: ASA and Brilique(ticagrelor) for 12 months followed by 12 months of ASA monotherapy. Stable Coronary Artery Disease (CAD) patients: ASA and clopidogrel for 12 months followed by 12 months of ASA monotherapy. Dosage and frequency: Brilique(Ticagrelor): 90 mg b.i.d. ASA: of 75mg qd (- ≤ 100 mg qd) Clopidogrel: 75 mg qd Ticagrelor: Comparison of 1 month of ticagrelor and aspirin followed by 23 months of ticagrelor monotherapy versus 12 months of standard dual anti platelet therapy (DAPT) followed by aspirin monotherapy. Acetylsalicylic Acid: Comparison of 1 month of ticagrelor and aspirin followed by 23 months of ticagrelor monotherapy versus 12 months of standard dual anti platelet therapy (DAPT) followed by aspirin monotherapy Clopidogrel: Active Comparator: Reference treatment strategy Acute Coronary Syndrome (ACS) patients incl. unstable angina (UA) patients: ASA and Brilique(ticagrelor) for
Measure Participants	7980	7988
Count of Participants [Participants]	64 0.8%	64 0.8%

9. Secondary Outcome

Title	Number of Participants With a Bleeding Academic Research Consortium (BARC) 3 or 5 Bleeding
Description	BARC definition. We only considered BARC 3 or 5 for this secondary safety endpoint. Type 3: Clinical, laboratory, and/or imaging evidence of bleeding with: Type 3a: Overt bleeding + Hb drop of 3 to < 5 g/dL (provided Hb drop is related to bleed) Any transfusion with overt bleeding Type 3b: Overt bleeding + Hb drop ≥5 g/dL (provided Hb drop is related to bleed) Cardiac tamponade Bleeding requiring surgical intervention (excluding dental/nasal/skin/haemorrhoid) Bleeding requiring intravenous vasoactive agents Type 3c: Intracranial haemorrhage (does not include microbleeds or haemorrhagic transformation, does include intraspinal) Subcategories confirmed by autopsy or imaging or lumbar puncture Intraocular bleed compromising vision. Type 5: Fatal bleeding Type 5a: • Probable fatal bleeding; no autopsy or imaging confirmation but clinically suspicious Type 5b: Definite fatal bleeding; overt bleeding or autopsy or imaging confirmation
Time Frame	2 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Experimental Treatment Strategy	Reference Treatment Strategy
Arm/Group Description	All patients in the treatment group will receive acetylsalicylic acid (ASA) and ticagrelor for 1 month followed by 23 months of ticagrelor monotherapy. Dosage and frequency: Ticagrelor: 90 mg b.i.d. ASA: of 75mg qd (- ≤ 100 mg qd) Ticagrelor: Comparison of 1 month of ticagrelor and aspirin followed by 23 months of ticagrelor monotherapy versus 12 months of standard dual anti platelet therapy (DAPT) followed by aspirin monotherapy. Acetylsalicylic Acid: Comparison of 1 month of ticagrelor and aspirin followed by 23 months of ticagrelor monotherapy versus 12 months of standard dual anti platelet therapy (DAPT) followed by aspirin monotherapy	Acute Coronary Syndrome (ACS) patients incl. unstable angina (UA) patients: ASA and Brilique(ticagrelor) for 12 months followed by 12 months of ASA monotherapy. Stable Coronary Artery Disease (CAD) patients: ASA and clopidogrel for 12 months followed by 12 months of ASA monotherapy. Dosage and frequency: Brilique(Ticagrelor): 90 mg b.i.d. ASA: of 75mg qd (- ≤ 100 mg qd) Clopidogrel: 75 mg qd Ticagrelor: Comparison of 1 month of ticagrelor and aspirin followed by 23 months of ticagrelor monotherapy versus 12 months of standard dual anti platelet therapy (DAPT) followed by aspirin monotherapy. Acetylsalicylic Acid: Comparison of 1 month of ticagrelor and aspirin followed by 23 months of ticagrelor monotherapy versus 12 months of standard dual anti platelet therapy (DAPT) followed by aspirin monotherapy Clopidogrel: Active Comparator: Reference treatment strategy Acute Coronary Syndrome (ACS) patients incl. unstable angina (UA) patients: ASA and Brilique(ticagrelor) for
Measure Participants	7980	7988
Count of Participants [Participants]	163 2%	169 2.1%

Adverse Events

Time Frame	monitored for 2 years
Arm/Group Title	Experimental Treatment Strategy		Reference Treatment Strategy
Arm/Group Description	All patients in the treatment group will receive acetylsalicylic acid (ASA) and ticagrelor for 1 month followed by 23 months of ticagrelor monotherapy. Dosage and frequency: Ticagrelor: 90 mg b.i.d. ASA: of 75mg qd (- ≤ 100 mg qd) Ticagrelor: Comparison of 1 month of ticagrelor and aspirin followed by 23 months of ticagrelor monotherapy versus 12 months of standard dual anti platelet therapy (DAPT) followed by aspirin monotherapy. Acetylsalicylic Acid: Comparison of 1 month of ticagrelor and aspirin followed by 23 months of ticagrelor monotherapy versus 12 months of standard dual anti platelet therapy (DAPT) followed by aspirin monotherapy		Acute Coronary Syndrome (ACS) patients incl. unstable angina (UA) patients: ASA and Brilique(ticagrelor) for 12 months followed by 12 months of ASA monotherapy. Stable Coronary Artery Disease (CAD) patients: ASA and clopidogrel for 12 months followed by 12 months of ASA monotherapy. Dosage and frequency: Brilique(Ticagrelor): 90 mg b.i.d. ASA: of 75mg qd (- ≤ 100 mg qd) Clopidogrel: 75 mg qd Ticagrelor: Comparison of 1 month of ticagrelor and aspirin followed by 23 months of ticagrelor monotherapy versus 12 months of standard dual anti platelet therapy (DAPT) followed by aspirin monotherapy. Acetylsalicylic Acid: Comparison of 1 month of ticagrelor and aspirin followed by 23 months of ticagrelor monotherapy versus 12 months of standard dual anti platelet therapy (DAPT) followed by aspirin monotherapy Clopidogrel: Active Comparator: Reference treatment strategy Acute Coronary Syndrome (ACS) patients incl. unstable angina (UA) patients: ASA and Brilique(ticagrelor) for
All Cause Mortality
	Experimental Treatment Strategy		Reference Treatment Strategy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	224/7980 (2.8%)		253/7988 (3.2%)
Serious Adverse Events
	Experimental Treatment Strategy		Reference Treatment Strategy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1459/7980 (18.3%)		1543/7988 (19.3%)
Cardiac disorders
new Q-wave MI	83/7980 (1%)		103/7988 (1.3%)
MI	248/7980 (3.1%)		250/7988 (3.1%)
Vascular disorders
stroke	162/7980 (2%)		164/7988 (2.1%)
revascularisation	739/7980 (9.3%)		793/7988 (9.9%)
definite stent thrombosis	64/7980 (0.8%)		64/7988 (0.8%)
BARC 3 or 5 bleeding	163/7980 (2%)		169/7988 (2.1%)
Other (Not Including Serious) Adverse Events
	Experimental Treatment Strategy		Reference Treatment Strategy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/7980 (0%)		0/7988 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.