Efficacy and Safety of Low-dose Ticagrelor

• Sponsor: First Affiliated Hospital of Harbin Medical University (Other)
• Overall Status: Completed
• CT.gov ID: NCT03381742
• Collaborator: Beijing Anzhen Hospital (Other), The First Affiliated Hospital of Dalian Medical University (Other), The Central Hospital of Jia Mu Si City (Other), The First Affiliated Hospital of Kunming Medical College (Other), RenJi Hospital (Other), Tianjin Medical University General Hospital (Other), Weifang People's Hospital (Other), Wuhan Union Hospital, China (Other), Shengjing Hospital (Other), Shaanxi Provincial People's Hospital (Other)
• Enrollment: 3,043
• Location: 1
• Arms: 4
• Actual Duration (Months): 14
• Patients Per Site Per Month: 216.9

Study Details

Study Description

Brief Summary

Guideline recommendations on the use of dual antiplatelet therapy have been formulated that ticagrelor 90 mg twice daily plus aspirin in preference to clopidogrel 75mg daily plus aspirin for ACS patients. Recent study found that ticagrelor 90mg twice a day orally could significantly reduce the occurrence of clopidogrel resistance and adverse cardiovascular events. The previous studies have reported that half-dose ticagrelor had the similar inhibitory effect on platelet aggregation as the standard-dose ticagrelor, which was significantly stronger than that in the clopidogrel group. One-quarter standard-dose ticagrelor provided greater degree of platelet inhibition than standard dose clopidogrel in Chinese patients with stable CAD. But large-scale clinical trials are still needed to confirm the effects of low-dose ticagrelor on platelet function in Chinese patients with coronary heart disease.

Condition or Disease	Intervention/Treatment	Phase
Coronary Artery Disease	Drug: Ticagrelor; Drug: ticagrelor; Drug: ticagrelor; Drug: clopidogrel	Phase 2/Phase 3

Detailed Description

Dual Antiplatelet Therapy (DAPT) with aspirin and P2Y12 receptor inhibitor remains a cornerstone in the secondary prevention of coronary artery disease (CAD). Clopidogrel is one of the most commonly used antithrombotic agent that inhibits the platelet P2Y(12) adenosine diphosphate (ADP) receptor.

Ticagrelor is an oral, reversibly-binding, direct-acting P2Y12 receptor antagonist used clinically for the prevention of atherothrombotic events in patients with acute coronary syndromes (ACS). Guideline recommendations on the use of dual antiplatelet therapy have been formulated that ticagrelor 90 mg twice daily plus aspirin in preference to clopidogrel 75mg daily plus aspirin for ACS patients. Recent study found that ticagrelor 90mg twice a day orally could significantly reduce the occurrence of clopidogrel resistance and adverse cardiovascular events. The previous studies have reported that half-dose ticagrelor had the similar inhibitory effect on platelet aggregation as the standard-dose ticagrelor, which was significantly stronger than that in the clopidogrel group. One-quarter standard-dose ticagrelor provided greater degree of platelet inhibition than standard dose clopidogrel in Chinese patients with stable CAD. But large-scale clinical trials are still needed to confirm the effects of low-dose ticagrelor on platelet function in Chinese patients with coronary heart disease.

Study Design

• Study Type: Interventional
• Actual Enrollment: 3043 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Efficacy and Safety of Different Ticagrelor Regimens Versus Clopidogrel in Patients With Coronary Artery Disease: a Retrospective Multicenter Study (SUPERIOR)
• Actual Study Start Date: Dec 13, 2017
• Actual Primary Completion Date: Dec 13, 2018
• Actual Study Completion Date: Feb 13, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ticagrelor 45mg bidpo. To observe the efficacy and safety of ticagrelor 45mg bidpo. in patients with coronary artery disease.	Drug: Ticagrelor; ticagrelor 45 mg twice daily for 5 consecutive days at least.
Experimental: ticagrelor 90mg qdpo. To observe the efficacy and safety of ticagrelor 90mg qdpo. in patients with coronary artery disease.	Drug: ticagrelor; ticagrelor 90 mg once daily for 5 consecutive days at least.
Active Comparator: ticagrelor 90mg bidpo. To observe the efficacy and safety of ticagrelor 90mg bidpo. in patients with coronary artery disease.	Drug: ticagrelor; ticagrelor 90 mg twice daily for 5 consecutive days at least.
Active Comparator: clopidogrel 75mg qdpo. To observe the efficacy and safety of clopidogrel 75mg qdpo. in patients with coronary artery disease.	Drug: clopidogrel; clopidogrel 75 mg once daily for 5 consecutive days at least.

Outcome Measures

Primary Outcome Measures

1. ADP-induced Inhibition of Platelet Aggregation [up to 5 days]

   The venous blood samples for platelet function test were drawn after an overnight fast, at 12 hours post-last study-drug dose for subjects receiving twice-daily administrations, and at 24 hours post-last study-drug dose for subjects treated with once-daily regimens. The blood was collected in an evacuated vacuum tube containing 3.2% trisodium citrate and lithium heparin. Then the samples were processed within two hours of blood draw according to standard operating procedure. The physical properties of samples were analyzed using Thromboelastography (TEG) Hemostasis Analyzer (CFMS LEPU-8800, Lepu Medical Technology Co., Ltd, Beijing, China) and automated analytical software. TEG test used four channels to detect the effects of anti-platelet therapy via the arachidonic acid (AA) and ADP pathways. TEG test results were expressed in terms of ADP-induced inhibition of platelet aggregation (IPA, range 0% - 100%), with higher values indicating greater platelet inhibition.

2. Number of Participants With Bleeding (Major or Minor Bleeding) [up to 5 days]

   Major bleeding was defined as type ≥ 3 and minor bleeding as types 1 and 2, in accordance to the Bleeding Academic Research Consortium classification. (Mehran R et al. Standardized bleeding definitions for cardiovascular clinical trials: a consensus report from the Bleeding Academic Research Consortium. Circulation. 2011 Jun 14;123(23):2736-47. doi: 10.1161/CIRCULATIONAHA.110.009449.)

Secondary Outcome Measures

1. ADP-induced Platelet-fibrin Clot Strength (MA) [up to 5 days]

   The physical properties of samples were analyzed using Thromboelastography (TEG) Hemostasis Analyzer (CFMS LEPU-8800, Lepu Medical Technology Co., Ltd, Beijing, China) and automated analytical software. TEG test used four channels to detect the effects of anti-platelet therapy via the arachidonic acid (AA) and ADP pathways. TEG test results were expressed in terms of ADP-induced platelet-fibrin clot strength (MA). A MA>47mm was shown to have a high predictive value for 3-year post-PCI ischemic events during dual antiplatelet therapy. Moreover, ROC curve and quartile analysis suggested MA<31 mm as a predictive value for post-PCI bleeding events (J Am Coll Cardiol. 2013;62(24):2261-73. doi: 10.1016/j.jacc.2013.07.101.).

2. Number of Participants With High On-Treatment Platelet Reactivity (HTPR) [up to 5 days]

   HTPR was defined as IPA ≤ 30% and MA ≥ 47 mm.

3. Number of Participants With Cardiovascular Event (Cardiovascular Death, New-onset Myocardial Infarction, or Stroke) [up to 5 days]

   Cardiovascular death was defined as sudden cardiac death, fatal myocardial infarction, death due to heart failure, or death due to other cardiovascular causes. Stroke was defined as the focal loss of neurologic function caused by an ischemic or a hemorrhagic event with residual symptoms lasting at least 24 hours or eventually leading to death.

4. Number of Participants With New-onset Dyspnea [up to 5 days]

   New-onset dyspnea in patients without previous history of dyspnea

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Patients with coronary artery disease

Exclusion Criteria:

• younger than 18 years of age;

• anti-platelet therapy with clopidogrel or ticagrelor for less than 5 days;

• previous or current treatment with any other potentially confounding drugs.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Thromboela-Stogram	Beijing		China	100001

Sponsors and Collaborators

• First Affiliated Hospital of Harbin Medical University
• Beijing Anzhen Hospital
• The First Affiliated Hospital of Dalian Medical University
• The Central Hospital of Jia Mu Si City
• The First Affiliated Hospital of Kunming Medical College
• RenJi Hospital
• Tianjin Medical University General Hospital
• Weifang People's Hospital
• Wuhan Union Hospital, China
• Shengjing Hospital
• Shaanxi Provincial People's Hospital

Investigators

• Principal Investigator: Yue Li, MD, Cardiovascular Department, the First Affiliated Hospital of Harbin Medical University

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Aug 16, 2019

More Information

Publications

None provided.

• Responsible Party: First Affiliated Hospital of Harbin Medical University
• ClinicalTrials.gov Identifier: NCT03381742
• Other Study ID Numbers: ACS-2
• First Posted: Dec 22, 2017
• Last Update Posted: Sep 30, 2019
• Last Verified: Jun 1, 2019

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Clopidogrel; Ticagrelor

Study Results

Participant Flow

Recruitment Details	3,737 CAD patients who received either clopidogrel or ticagrelor therapy and underwent TEG test from 11 medical centers. Among these patients, 1,725 subjects were treated with clopidogrel and 2,012 subjects were treated with different ticagrelor regimens.

Arm/Group Title	Ticagrelor 45mg Bidpo.	Ticagrelor 90mg Bidpo.	Clopidogrel 75mg Qdpo.	Ticagrelor 90mg Qdpo.
Arm/Group Description	To observe the efficacy and safety of ticagrelor 45mg bidpo. in patients with coronary artery disease. Ticagrelor: ticagrelor 45 mg twice daily for 5 consecutive days at least.	To observe the efficacy and safety of ticagrelor 90mg bidpo. in patients with coronary artery disease. ticagrelor: ticagrelor 90 mg twice daily for 5 consecutive days at least.	To observe the efficacy and safety of clopidogrel 75mg qdpo. in patients with coronary artery disease. clopidogrel: clopidogrel 75 mg once daily for 5 consecutive days at least.	To observe the efficacy and safety of ticagrelor 90mg qdpo. in patients with coronary artery disease. Ticagrelor: ticagrelor 90 mg once daily for 5 consecutive days at least.
Period Title: Overall Study
STARTED	525	501	1511	506
COMPLETED	525	501	1511	506
NOT COMPLETED	0	0	0	0

Baseline Characteristics

Arm/Group Title	Clopidogrel 75mg Qdpo.	Ticagrelor 90mg Bidpo.	Ticagrelor 45mg Bidpo.	Ticagrelor 90mg Qdpo.	Total
Arm/Group Description	To observe the efficacy and safety of clopidogrel 75mg qdpo. in patients with coronary artery disease. clopidogrel: clopidogrel 75 mg once daily for 5 consecutive days at least.	To observe the efficacy and safety of ticagrelor 90mg bidpo. in patients with coronary artery disease. ticagrelor: ticagrelor 90 mg twice daily for 5 consecutive days at least.	To observe the efficacy and safety of ticagrelor 45mg bidpo. in patients with coronary artery disease. Ticagrelor: ticagrelor 45 mg twice daily for 5 consecutive days at least.	To observe the efficacy and safety of ticagrelor 90mg qdpo. in patients with coronary artery disease. ticagrelor: ticagrelor 90 mg once daily for 5 consecutive days at least.	Total of all reporting groups
Overall Participants	1511	501	525	506	3043
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	63	61	62	62	62
Sex: Female, Male (Count of Participants)
Female	532 35.2%	159 31.7%	201 38.3%	237 46.8%	1129 37.1%
Male	979 64.8%	342 68.3%	324 61.7%	269 53.2%	1914 62.9%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	1511 100%	501 100%	525 100%	506 100%	3043 100%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%	0 0%	0 0%
White	0 0%	0 0%	0 0%	0 0%	0 0%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
China	1511 100%	501 100%	525 100%	506 100%	3043 100%
Weight (kg) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [kg]	70	70	70	70	70
smoking (Count of Participants)
Count of Participants [Participants]	736 48.7%	234 46.7%	226 43%	202 39.9%	1398 45.9%
Hypertension (Count of Participants)
Count of Participants [Participants]	879 58.2%	243 48.5%	332 63.2%	287 56.7%	1741 57.2%
diabetes mellitus (Count of Participants)
Count of Participants [Participants]	426 28.2%	126 25.1%	161 30.7%	117 23.1%	830 27.3%
chronic kidney disease (Count of Participants)
Count of Participants [Participants]	60 4%	13 2.6%	25 4.8%	13 2.6%	111 3.6%
percutaneous coronary intervention (Count of Participants)
Count of Participants [Participants]	1056 69.9%	326 65.1%	241 45.9%	179 35.4%	1802 59.2%
coronary artery bypass grafting (Count of Participants)
Count of Participants [Participants]	12 0.8%	2 0.4%	2 0.4%	1 0.2%	17 0.6%
total cholesterol (mmol/L) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [mmol/L]	4.2	3.9	4.3	4.7	4.24
triglyceride (mmol/L) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [mmol/L]	1.6	1.9	1.7	1.6	1.67
high density lipoprotein (mmol/L) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [mmol/L]	1.1	1.1	1.1	1.2	1.1
low density lipoprotein (mmol/L) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [mmol/L]	2.6	2.8	2.7	2.9	2.68
creatinine (μmol/L) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [μmol/L]	71	69.7	68.7	67.7	69.9
uric acid (μmol/L) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [μmol/L]	330	338	323	320	328.4
aspirin use (Count of Participants)
Count of Participants [Participants]	1429 94.6%	446 89%	475 90.5%	443 87.5%	2793 91.8%
acute myocardial infarction (Count of Participants)
Count of Participants [Participants]	568 37.6%	180 35.9%	98 18.7%	49 9.7%	895 29.4%

Outcome Measures

1. Primary Outcome

Title	ADP-induced Inhibition of Platelet Aggregation
Description	The venous blood samples for platelet function test were drawn after an overnight fast, at 12 hours post-last study-drug dose for subjects receiving twice-daily administrations, and at 24 hours post-last study-drug dose for subjects treated with once-daily regimens. The blood was collected in an evacuated vacuum tube containing 3.2% trisodium citrate and lithium heparin. Then the samples were processed within two hours of blood draw according to standard operating procedure. The physical properties of samples were analyzed using Thromboelastography (TEG) Hemostasis Analyzer (CFMS LEPU-8800, Lepu Medical Technology Co., Ltd, Beijing, China) and automated analytical software. TEG test used four channels to detect the effects of anti-platelet therapy via the arachidonic acid (AA) and ADP pathways. TEG test results were expressed in terms of ADP-induced inhibition of platelet aggregation (IPA, range 0% - 100%), with higher values indicating greater platelet inhibition.
Time Frame	up to 5 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Clopidogrel 75mg Qdpo.	Ticagrelor 90mg Bidpo.	Ticagrelor 45mg Bidpo.	Ticagrelor 90mg Qdpo.
Arm/Group Description	To observe the efficacy and safety of clopidogrel 75mg qdpo. in patients with coronary artery disease. clopidogrel: clopidogrel 75 mg once daily for 5 consecutive days at least.	To observe the efficacy and safety of ticagrelor 90mg bidpo. in patients with coronary artery disease. ticagrelor: ticagrelor 90 mg twice daily for 5 consecutive days at least.	To observe the efficacy and safety of ticagrelor 45mg bidpo. in patients with coronary artery disease. Ticagrelor: ticagrelor 45 mg twice daily for 5 consecutive days at least.	To observe the efficacy and safety of ticagrelor 90mg qdpo. in patients with coronary artery disease. ticagrelor: ticagrelor 90 mg once daily for 5 consecutive days at least.
Measure Participants	1511	501	525	506
Median (Inter-Quartile Range) [percentage of inhibition of platelet agg]	54.9	80.6	73.6	66

2. Primary Outcome

Title	Number of Participants With Bleeding (Major or Minor Bleeding)
Description	Major bleeding was defined as type ≥ 3 and minor bleeding as types 1 and 2, in accordance to the Bleeding Academic Research Consortium classification. (Mehran R et al. Standardized bleeding definitions for cardiovascular clinical trials: a consensus report from the Bleeding Academic Research Consortium. Circulation. 2011 Jun 14;123(23):2736-47. doi: 10.1161/CIRCULATIONAHA.110.009449.)
Time Frame	up to 5 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Clopidogrel 75mg Qdpo.	Ticagrelor 90mg Bidpo.	Ticagrelor 45mg Bidpo.	Ticagrelor 90mg Qdpo.
Arm/Group Description	To observe the efficacy and safety of clopidogrel 75mg qdpo. in patients with coronary artery disease. clopidogrel: clopidogrel 75 mg once daily for 5 consecutive days at least.	To observe the efficacy and safety of ticagrelor 90mg bidpo. in patients with coronary artery disease. ticagrelor: ticagrelor 90 mg twice daily for 5 consecutive days at least.	To observe the efficacy and safety of ticagrelor 45mg bidpo. in patients with coronary artery disease. Ticagrelor: ticagrelor 45 mg twice daily for 5 consecutive days at least.	To observe the efficacy and safety of ticagrelor 90mg qdpo. in patients with coronary artery disease. ticagrelor: ticagrelor 90 mg once daily for 5 consecutive days at least.
Measure Participants	1511	501	525	506
Minor bleeding	15 1%	30 6%	14 2.7%	9 1.8%
Major bleeding	0 0%	0 0%	0 0%	0 0%
No bleeding	1496 99%	471 94%	511 97.3%	497 98.2%

3. Secondary Outcome

Title	ADP-induced Platelet-fibrin Clot Strength (MA)
Description	The physical properties of samples were analyzed using Thromboelastography (TEG) Hemostasis Analyzer (CFMS LEPU-8800, Lepu Medical Technology Co., Ltd, Beijing, China) and automated analytical software. TEG test used four channels to detect the effects of anti-platelet therapy via the arachidonic acid (AA) and ADP pathways. TEG test results were expressed in terms of ADP-induced platelet-fibrin clot strength (MA). A MA>47mm was shown to have a high predictive value for 3-year post-PCI ischemic events during dual antiplatelet therapy. Moreover, ROC curve and quartile analysis suggested MA<31 mm as a predictive value for post-PCI bleeding events (J Am Coll Cardiol. 2013;62(24):2261-73. doi: 10.1016/j.jacc.2013.07.101.).
Time Frame	up to 5 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Clopidogrel 75mg Qdpo.	Ticagrelor 90mg Bidpo.	Ticagrelor 45mg Bidpo.	Ticagrelor 90mg Qdpo.
Arm/Group Description	To observe the efficacy and safety of clopidogrel 75mg qdpo. in patients with coronary artery disease. clopidogrel: clopidogrel 75 mg once daily for 5 consecutive days at least.	To observe the efficacy and safety of ticagrelor 90mg bidpo. in patients with coronary artery disease. ticagrelor: ticagrelor 90 mg twice daily for 5 consecutive days at least.	To observe the efficacy and safety of ticagrelor 45mg bidpo. in patients with coronary artery disease. Ticagrelor: ticagrelor 45 mg twice daily for 5 consecutive days at least.	To observe the efficacy and safety of ticagrelor 90mg qdpo. in patients with coronary artery disease. ticagrelor: ticagrelor 90 mg once daily for 5 consecutive days at least.
Measure Participants	1511	501	525	506
Median (Inter-Quartile Range) [mm]	40.3	28.4	32.3	34.05

4. Secondary Outcome

Title	Number of Participants With High On-Treatment Platelet Reactivity (HTPR)
Description	HTPR was defined as IPA ≤ 30% and MA ≥ 47 mm.
Time Frame	up to 5 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Clopidogrel 75mg Qdpo.	Ticagrelor 90mg Bidpo.	Ticagrelor 45mg Bidpo.	Ticagrelor 90mg Qdpo.
Arm/Group Description	To observe the efficacy and safety of clopidogrel 75mg qdpo. in patients with coronary artery disease. clopidogrel: clopidogrel 75 mg once daily for 5 consecutive days at least.	To observe the efficacy and safety of ticagrelor 90mg bidpo. in patients with coronary artery disease. ticagrelor: ticagrelor 90 mg twice daily for 5 consecutive days at least.	To observe the efficacy and safety of ticagrelor 45mg bidpo. in patients with coronary artery disease. Ticagrelor: ticagrelor 45 mg twice daily for 5 consecutive days at least.	To observe the efficacy and safety of ticagrelor 90mg qdpo. in patients with coronary artery disease. ticagrelor: ticagrelor 90 mg once daily for 5 consecutive days at least.
Measure Participants	1511	501	525	506
HTPR	317 21%	13 2.6%	23 4.4%	32 6.3%
Non-HTPR	1194 79%	488 97.4%	502 95.6%	474 93.7%

5. Secondary Outcome

Title	Number of Participants With Cardiovascular Event (Cardiovascular Death, New-onset Myocardial Infarction, or Stroke)
Description	Cardiovascular death was defined as sudden cardiac death, fatal myocardial infarction, death due to heart failure, or death due to other cardiovascular causes. Stroke was defined as the focal loss of neurologic function caused by an ischemic or a hemorrhagic event with residual symptoms lasting at least 24 hours or eventually leading to death.
Time Frame	up to 5 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Clopidogrel 75mg Qdpo.	Ticagrelor 90mg Bidpo.	Ticagrelor 45mg Bidpo.	Ticagrelor 90mg Qdpo.
Arm/Group Description	To observe the efficacy and safety of clopidogrel 75mg qdpo. in patients with coronary artery disease. clopidogrel: clopidogrel 75 mg once daily for 5 consecutive days at least.	To observe the efficacy and safety of ticagrelor 90mg bidpo. in patients with coronary artery disease. ticagrelor: ticagrelor 90 mg twice daily for 5 consecutive days at least.	To observe the efficacy and safety of ticagrelor 45mg bidpo. in patients with coronary artery disease. Ticagrelor: ticagrelor 45 mg twice daily for 5 consecutive days at least.	To observe the efficacy and safety of ticagrelor 90mg qdpo. in patients with coronary artery disease. ticagrelor: ticagrelor 90 mg once daily for 5 consecutive days at least.
Measure Participants	1511	501	525	506
Participants with cardiovascular death	0 0%	0 0%	0 0%	0 0%
Participants without cardiovascular events	1511 100%	501 100%	525 100%	506 100%
Participants with new-onset myocardial infarction	0 0%	0 0%	0 0%	0 0%
Participants with stroke	0 0%	0 0%	0 0%	0 0%

6. Secondary Outcome

Title	Number of Participants With New-onset Dyspnea
Description	New-onset dyspnea in patients without previous history of dyspnea
Time Frame	up to 5 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Clopidogrel 75mg Qdpo.	Ticagrelor 90mg Bidpo.	Ticagrelor 45mg Bidpo.	Ticagrelor 90mg Qdpo.
Arm/Group Description	To observe the efficacy and safety of clopidogrel 75mg qdpo. in patients with coronary artery disease. clopidogrel: clopidogrel 75 mg once daily for 5 consecutive days at least.	To observe the efficacy and safety of ticagrelor 90mg bidpo. in patients with coronary artery disease. ticagrelor: ticagrelor 90 mg twice daily for 5 consecutive days at least.	To observe the efficacy and safety of ticagrelor 45mg bidpo. in patients with coronary artery disease. Ticagrelor: ticagrelor 45 mg twice daily for 5 consecutive days at least.	To observe the efficacy and safety of ticagrelor 90mg qdpo. in patients with coronary artery disease. ticagrelor: ticagrelor 90 mg once daily for 5 consecutive days at least.
Measure Participants	1511	501	525	506
Participants with new-onset dyspnea	34 2.3%	29 5.8%	32 6.1%	28 5.5%
Participants without new-onset dyspne	1477 97.7%	472 94.2%	493 93.9%	478 94.5%

Adverse Events

Time Frame	up to 5 days
Arm/Group Title	Clopidogrel 75mg Qdpo.		Ticagrelor 90mg Bidpo.		Ticagrelor 45mg Bidpo.		Ticagrelor 90mg Qdpo.
Arm/Group Description	To observe the efficacy and safety of clopidogrel 75mg qdpo. in patients with coronary artery disease. clopidogrel: clopidogrel 75 mg once daily for 5 consecutive days at least.		To observe the efficacy and safety of ticagrelor 90mg bidpo. in patients with coronary artery disease. ticagrelor: ticagrelor 90 mg twice daily for 5 consecutive days at least.		To observe the efficacy and safety of ticagrelor 45mg bidpo. in patients with coronary artery disease. Ticagrelor: ticagrelor 45 mg twice daily for 5 consecutive days at least.		To observe the efficacy and safety of ticagrelor 90mg qdpo. in patients with coronary artery disease. ticagrelor: ticagrelor 90 mg once daily for 5 consecutive days at least.
All Cause Mortality
	Clopidogrel 75mg Qdpo.		Ticagrelor 90mg Bidpo.		Ticagrelor 45mg Bidpo.		Ticagrelor 90mg Qdpo.
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1511 (0%)		0/501 (0%)		0/525 (0%)		0/506 (0%)
Serious Adverse Events
	Clopidogrel 75mg Qdpo.		Ticagrelor 90mg Bidpo.		Ticagrelor 45mg Bidpo.		Ticagrelor 90mg Qdpo.
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1511 (0%)		0/501 (0%)		0/525 (0%)		0/506 (0%)
Other (Not Including Serious) Adverse Events
	Clopidogrel 75mg Qdpo.		Ticagrelor 90mg Bidpo.		Ticagrelor 45mg Bidpo.		Ticagrelor 90mg Qdpo.
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1511 (0%)		0/501 (0%)		0/525 (0%)		0/506 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT 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.