RESPOND: A Study of the Antiplatelet Effects Comparing Ticagrelor (Ticag. - AZD6140) With Clopidogrel (Clop.) Responder and Non-responders

• Sponsor: AstraZeneca (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00642811
• Collaborator: (none)
• Enrollment: 98
• Locations: 10
• Arms: 2
• Duration (Months): 10
• Patients Per Site: 9.8
• Patients Per Site Per Month: 1

Study Details

Study Description

Brief Summary

The purpose of this study is to see how Ticagrelor, a new oral reversible anti-platelet medication, affects platelets. Anti-platelet agents are medications that block the formation of blood clots by preventing the clumping of platelets. Blood clots prevent us from bleeding, but when they form inside the arteries their formation is linked to a risk of medical problems such as heart attack and stroke. This study investigated the effect of Ticagrelor on inhibition of platelet aggregation compared with clopidogrel in patients previously identified as non-responsive to clopidogrel.

Condition or Disease	Intervention/Treatment	Phase
Stable Coronary Artery Disease	Drug: Ticagrelor; Drug: Clopidogrel; Drug: Aspirin	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 98 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomised, Double-Blind, Outpatient, Crossover Study of the Anti-platelet Effects of Ticagrelor Compared With Clopidogrel in Patients With Stable Coronary Artery Disease Previously Identified as Clopidogrel Non-responders or Responders [RESPOND]
• Study Start Date: May 1, 2008
• Actual Primary Completion Date: Mar 1, 2009
• Actual Study Completion Date: Mar 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 Aspirin + Ticagrelor	Drug: Ticagrelor; Tablets, Oral, 90 mg; 180 mg loading dose followed by 90 mg twice daily for 2 weeks; Drug: Aspirin; Tablets, Oral, 75 mg to 100 mg once daily. Aspirin obtained locally by the investigator, according to local practice. The dose remained constant throughout the study
Active Comparator: 2 Aspirin + Clopidogrel	Drug: Clopidogrel; (over encapsulated) capsule, Oral, 75 mg; 600 mg loading dose followed by 75 mg once daily for 2 weeks; Other Names: Plavix ; Drug: Aspirin; Tablets, Oral, 75 mg to 100 mg once daily. Aspirin obtained locally by the investigator, according to local practice. The dose remained constant throughout the study

Outcome Measures

Primary Outcome Measures

1. Proportion of Clopidogrel Non-responders Who Responded to Clopidogrel or Ticagrelor. - Comparing Ticag. (Day 28 of Clop. to Ticag., and Day 14 of Ticag. to Clop.) Versus Clop. (Day 14 of Clop. to Ticag., and Day 28 of Ticag. to Clop.) [Day 14 and Day 28, 4 Hrs Post Dose.]

   The primary definition of response to treatment is IPA >10% post treatment. The response is reported as percentage of participants of each treatment. Please refer to the protocol section for details about the interventions administered. IPA(%)=(PAb-PAt)/PAb*100. PA (platelet aggregation) is measured by LTA (Light Transmittance Aggregometry). PAb is the response at baseline (last measurement before study drug) and PAt is a response at post-treatment. IPA=0% means no PA inhibition and 100% means 100% PA inhibition.

2. Proportion of Clopidogrel Non-responders Who Responded to Clopidogrel or Ticagrelor. - Comparing Ticag. (Day 28 of Clop. to Ticag., and Day 14 of Ticag. to Clop.) Versus Clop. (Day 14 of Clop. to Ticag., and Day 28 of Ticag. to Clop. [Day 14, and day 28, 4 hours post dose]

   The secondary definition of response to treatment is IPA >50% post treatment. The response is reported as percentage of participants of each treatment. Please refer to the protocol section for details about the interventions administered. IPA(%)=(PAb-PAt)/PAb*100. PA (platelet aggregation) is measured by LTA (Light Transmittance Aggregometry). PAb is the response at baseline (last measurement before study drug) and PAt is a response at post-treatment. IPA=0% means no PA inhibition and 100% means 100% PA inhibition.

Secondary Outcome Measures

1. Clopidogrel Responders Final Extent IPA Post Switching Treatment - Comparing Ticagrelor to Ticagrelor Versus Ticagrelor to Clopidogrel on Day 15 [Day 15, 4 hrs post switching]

   IPA(%)=(PAb-PAt)/PAb*100. PA (platelet aggregation) is measured by LTA (Light Transmittance Aggregometry). PAb is the response at baseline (last measurement before study drug) and PAt is a response at post-treatment. IPA=0% means no PA inhibition and 100% means 100% PA inhibition. Please refer to the protocol section for details about the interventions administered.

2. Clopidogrel Responders Final Extent IPA Post Switching Treatment - Comparing Ticagrelor to Ticagrelor Versus Ticagrelor to Clopidogrel on Day 28 [4 hrs post first dose on day 28]

   IPA(%)=(PAb-PAt)/PAb*100. PA (platelet aggregation) is measured by LTA (Light Transmittance Aggregometry). PAb is the response at baseline (last measurement before study drug) and PAt is a response at post-treatment. IPA=0% means no PA inhibition and 100% means 100% PA inhibition. Please refer to the protocol section for details about the interventions administered.

3. Clopidogrel Responders Final Extent IPA Post Switching Treatment - Comparing Clopidogrel to Clopidogrel Versus Clopidogrel to Ticagrelor on Day 15 [Day 15, 4 hrs post switching]

   IPA(%)=(PAb-PAt)/PAb*100. PA (platelet aggregation) is measured by LTA (Light Transmittance Aggregometry). PAb is the response at baseline (last measurement before study drug) and PAt is a response at post-treatment. IPA=0% means no PA inhibition and 100% means 100% PA inhibition. Please refer to the protocol section for details about the interventions administered.

4. Clopidogrel Responders Final Extent IPA Post Switching Treatment - Comparing Clopidogrel to Clopidogrel Versus Clopidogrel to Ticagrelor on Day 28 [4 hrs post first dose on day 28]

   IPA(%)=(PAb-PAt)/PAb*100. PA (platelet aggregation) is measured by LTA (Light Transmittance Aggregometry). PAb is the response at baseline (last measurement before study drug) and PAt is a response at post-treatment. IPA=0% means no PA inhibition and 100% means 100% PA inhibition. Please refer to the protocol section for details about the interventions administered.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Patients with documented stable Coronary Artery Disease (CAD) (stable angina, previous MI history, previous history of revascularization)

• Females of child bearing potential must have a negative pregnancy test prior to receiving study drug and be willing to use a hormonal contraceptive in addition to double barrier contraception

Exclusion Criteria:

• History of Acute Coronary Syndromes within 12 months of screening or need for revascularization (angioplasty or coronary artery bypass graft (CABG))

• Any acute or chronic unstable condition in the past 30 days

• Have increased bleeding risk, eg, recent gastrointestinal bleed, uncontrolled high blood pressure, low platelet count, recent major trauma

• History of intolerance or allergy to aspirin or clopidogrel

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Jonesboro	Arkansas	United States
2	Research Site	Ormond Beach	Florida	United States
3	Research Site	Baltimore	Maryland	United States
4	Research Site	Cincinnati	Ohio	United States
5	Research Site	Hamilton	Ontario	Canada
6	Research Site	Lachine		Canada
7	Research Site	Aalborg		Denmark
8	Research Site	Arhus		Denmark
9	Research Site	Esbjerg		Denmark
10	Research Site	Sheffield		United Kingdom

Sponsors and Collaborators

• AstraZeneca

Investigators

• Study Director: Jay Horrow, MD, AstraZeneca
• Principal Investigator: Paul Gurbel, md, Platelet & Thrombosis Research, LLC

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT00642811
• Other Study ID Numbers: D5130C00030
• First Posted: Mar 25, 2008
• Last Update Posted: Oct 4, 2011
• Last Verified: Aug 1, 2011

• Keywords provided by AstraZeneca: coronary artery disease (CAD); heart attack; stable angina
• Additional relevant MeSH terms: Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Aspirin; Clopidogrel; Ticagrelor

Study Results

Participant Flow

Arm/Group Title	Clopidogrel Non-responders - Clopidogrel to Ticagrelor	Clopidogrel Non-responders - Ticagrelor to Clopidogrel	Clopidogrel Responders - Clopidogrel to Clopidogrel	Clopidogrel Responders - Clopidogrel to Ticagrelor	Clopidogrel Responders - Ticagrelor to Clopidogrel	Clopidogrel Responders - Ticagrelor to Ticagrelor
Arm/Group Description	Non-responder definition: patients with an absolute difference of less than or equal to 10% between baseline and post-treatment platelet aggregation (maximum extent) with 20 μM ADP used as the agonist. Clopidogrel 600 mg loading dose followed by 75 mg once daily (od) for 2 weeks; switch to ticagrelor 180 mg loading dose followed by 90 mg twice daily (bd) for 2 weeks.	Non-responder definition: patients with an absolute difference of less than or equal to 10% between baseline and post-treatment platelet aggregation (maximum extent) with 20 μM ADP used as the agonist. Ticagrelor 180 mg loading dose followed by 90 mg twice daily (bd) for 2 weeks; switch to clopidogrel 600 mg loading dose followed by 75 mg once daily (od) for 2 weeks.	Responder definition: patients with an absolute difference greater than 10% between baseline and post-treatment platelet aggregation (maximum extent) with 20 μM ADP used as the agonist. Clopidogrel 600 mg loading dose followed by 75 mg once daily (od) for 2 weeks; stay on clopidogrel 75 mg once daily (od) for 2 weeks	Responder definition: patients with an absolute difference greater than 10% between baseline and post-treatment platelet aggregation (maximum extent) with 20 μM ADP used as the agonist. Clopidogrel 600 mg loading dose followed by 75 mg once daily (od) for 2 weeks; switch to ticagrelor 180 mg loading dose followed by 90 mg twice daily (bd) for 2 weeks.	Responder definition: patients with an absolute difference greater than 10% between baseline and post-treatment platelet aggregation (maximum extent) with 20 μM ADP used as the agonist. Ticagrelor 180 mg loading dose followed by 90 mg twice daily (bd) for 2 weeks; switch to clopidogrel 600 mg loading dose followed by 75 mg once daily (od) for 2 weeks.	Responder definition: patients with an absolute difference greater than 10% between baseline and post-treatment platelet aggregation (maximum extent) with 20 μM ADP used as the agonist. Ticagrelor 180 mg loading dose followed by 90 mg twice daily (bd) for 2 weeks; stay on ticagrelor 90 mg twice daily (bd) for 2 weeks.
Period Title: Overall Study
STARTED	20	21	13	16	14	14
COMPLETED	17	17	13	15	13	13
NOT COMPLETED	3	4	0	1	1	1

Baseline Characteristics

Arm/Group Title	Clopidogrel Non-responders - Clopidogrel to Ticagrelor	Clopidogrel Non-responders - Ticagrelor to Clopidogrel	Clopidogrel Responders - Clopidogrel to Clopidogrel	Clopidogrel Responders - Clopidogrel to Ticagrelor	Clopidogrel Responders - Ticagrelor to Clopidogrel	Clopidogrel Responders - Ticagrelor to Ticagrelor	Total
Arm/Group Description	Non-responder definition: patients with an absolute difference of less than or equal to 10% between baseline and post-treatment platelet aggregation (maximum extent) with 20 μM ADP used as the agonist	Non-responder definition: patients with an absolute difference of less than or equal to 10% between baseline and post-treatment platelet aggregation (maximum extent) with 20 μM ADP used as the agonist	Responder definition: patients with an absolute difference greater than 10% between baseline and post-treatment platelet aggregation (maximum extent) with 20 μM ADP used as the agonist	Responder definition: patients with an absolute difference greater than 10% between baseline and post-treatment platelet aggregation (maximum extent) with 20 μM ADP used as the agonist	Responder definition: patients with an absolute difference greater than 10% between baseline and post-treatment platelet aggregation (maximum extent) with 20 μM ADP used as the agonist	Responder definition: patients with an absolute difference greater than 10% between baseline and post-treatment platelet aggregation (maximum extent) with 20 μM ADP used as the agonist	Total of all reporting groups
Overall Participants	20	21	13	16	14	14	98
Age (year) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [year]	67.25 (8.12)	64.57 (6.31)	65.46 (8.68)	64.56 (8.56)	63.21 (9.23)	61.57 (8.22)	64.8 (7.95)
Sex: Female, Male (Count of Participants)
Female	5 25%	8 38.1%	3 23.1%	2 12.5%	3 21.4%	1 7.1%	22 22.4%
Male	15 75%	13 61.9%	10 76.9%	14 87.5%	11 78.6%	13 92.9%	76 77.6%

Outcome Measures

1. Primary Outcome

Title	Proportion of Clopidogrel Non-responders Who Responded to Clopidogrel or Ticagrelor. - Comparing Ticag. (Day 28 of Clop. to Ticag., and Day 14 of Ticag. to Clop.) Versus Clop. (Day 14 of Clop. to Ticag., and Day 28 of Ticag. to Clop.)
Description	The primary definition of response to treatment is IPA >10% post treatment. The response is reported as percentage of participants of each treatment. Please refer to the protocol section for details about the interventions administered. IPA(%)=(PAb-PAt)/PAb*100. PA (platelet aggregation) is measured by LTA (Light Transmittance Aggregometry). PAb is the response at baseline (last measurement before study drug) and PAt is a response at post-treatment. IPA=0% means no PA inhibition and 100% means 100% PA inhibition.
Time Frame	Day 14 and Day 28, 4 Hrs Post Dose.

Outcome Measure Data

Analysis Population Description

Intent-to-treat analysis set: included patients who were assigned to a cohort, randomised to a treatment group, received at least one dose of study drug, and contributed post baseline data. 32 subjects had IPA data; but 1 subject missing a treatment arm, did not qualify for McNemar's test.

Arm/Group Title	Non-responder: Ticagrelor	Non-responder: Clopidogrel
Arm/Group Description	patients with an absolute difference of less than or equal to 10% between baseline and post-treatment platelet aggregation (maximum extent) with 20 μM ADP used as the agonist	patients with an absolute difference of less than or equal to 10% between baseline and post-treatment platelet aggregation (maximum extent) with 20 μM ADP used as the agonist
Measure Participants	31	31
Number [Percent of Participants]	100 500%	93.8 446.7%

2. Primary Outcome

Title	Proportion of Clopidogrel Non-responders Who Responded to Clopidogrel or Ticagrelor. - Comparing Ticag. (Day 28 of Clop. to Ticag., and Day 14 of Ticag. to Clop.) Versus Clop. (Day 14 of Clop. to Ticag., and Day 28 of Ticag. to Clop.
Description	The secondary definition of response to treatment is IPA >50% post treatment. The response is reported as percentage of participants of each treatment. Please refer to the protocol section for details about the interventions administered. IPA(%)=(PAb-PAt)/PAb*100. PA (platelet aggregation) is measured by LTA (Light Transmittance Aggregometry). PAb is the response at baseline (last measurement before study drug) and PAt is a response at post-treatment. IPA=0% means no PA inhibition and 100% means 100% PA inhibition.
Time Frame	Day 14, and day 28, 4 hours post dose

Outcome Measure Data

Analysis Population Description

Intent-to-treat analysis set: included patients who were assigned to a cohort, randomised to a treatment group, received at least one dose of study drug, and contributed post baseline data. 32 subjects had IPA data; but 1 subject missing a treatment arm, did not qualify for McNemar's test.

Arm/Group Title	Non-responder: Ticagrelor	Non-responder: Clopidogrel
Arm/Group Description	patients with an absolute difference of less than or equal to 10% between baseline and post-treatment platelet aggregation (maximum extent) with 20 μM ADP used as the agonist	patients with an absolute difference of less than or equal to 10% between baseline and post-treatment platelet aggregation (maximum extent) with 20 μM ADP used as the agonist
Measure Participants	31	31
Number [Percent of participants]	81.3 406.5%	25.0 119%

3. Secondary Outcome

Title	Clopidogrel Responders Final Extent IPA Post Switching Treatment - Comparing Ticagrelor to Ticagrelor Versus Ticagrelor to Clopidogrel on Day 15
Description	IPA(%)=(PAb-PAt)/PAb*100. PA (platelet aggregation) is measured by LTA (Light Transmittance Aggregometry). PAb is the response at baseline (last measurement before study drug) and PAt is a response at post-treatment. IPA=0% means no PA inhibition and 100% means 100% PA inhibition. Please refer to the protocol section for details about the interventions administered.
Time Frame	Day 15, 4 hrs post switching

Outcome Measure Data

Analysis Population Description

Intent-to-treat analysis set: included patients who were assigned to a cohort, randomised to a treatment group, received at least one dose of study drug, and contributed post baseline data.

Arm/Group Title	Responder: Ticagrelor	Responder: Clopidogrel
Arm/Group Description	patients with an absolute difference greater than 10% between baseline and post-treatment platelet aggregation (maximum extent) with 20 μM ADP used as the agonist	patients with an absolute difference greater than 10% between baseline and post-treatment platelet aggregation (maximum extent) with 20 μM ADP used as the agonist
Measure Participants	12	10
Least Squares Mean (95% Confidence Interval) [Percent]	66.7	65.3

4. Secondary Outcome

Title	Clopidogrel Responders Final Extent IPA Post Switching Treatment - Comparing Ticagrelor to Ticagrelor Versus Ticagrelor to Clopidogrel on Day 28
Description	IPA(%)=(PAb-PAt)/PAb*100. PA (platelet aggregation) is measured by LTA (Light Transmittance Aggregometry). PAb is the response at baseline (last measurement before study drug) and PAt is a response at post-treatment. IPA=0% means no PA inhibition and 100% means 100% PA inhibition. Please refer to the protocol section for details about the interventions administered.
Time Frame	4 hrs post first dose on day 28

Outcome Measure Data

Analysis Population Description

Intent-to-treat analysis set: included patients who were assigned to a cohort, randomised to a treatment group, received at least one dose of study drug, and contributed post baseline data.

Arm/Group Title	Responder: Ticagrelor	Responder: Clopidogrel
Arm/Group Description	patients with an absolute difference greater than 10% between baseline and post-treatment platelet aggregation (maximum extent) with 20 μM ADP used as the agonist	patients with an absolute difference greater than 10% between baseline and post-treatment platelet aggregation (maximum extent) with 20 μM ADP used as the agonist
Measure Participants	11	10
Least Squares Mean (95% Confidence Interval) [Percent]	91.0	61.2

5. Secondary Outcome

Title	Clopidogrel Responders Final Extent IPA Post Switching Treatment - Comparing Clopidogrel to Clopidogrel Versus Clopidogrel to Ticagrelor on Day 15
Description	IPA(%)=(PAb-PAt)/PAb*100. PA (platelet aggregation) is measured by LTA (Light Transmittance Aggregometry). PAb is the response at baseline (last measurement before study drug) and PAt is a response at post-treatment. IPA=0% means no PA inhibition and 100% means 100% PA inhibition. Please refer to the protocol section for details about the interventions administered.
Time Frame	Day 15, 4 hrs post switching

Outcome Measure Data

Analysis Population Description

Intent-to-treat analysis set: included patients who were assigned to a cohort, randomised to a treatment group, received at least one dose of study drug, and contributed post baseline data.

Arm/Group Title	Responder: Ticagrelor	Responder: Clopidogrel
Arm/Group Description	patients with an absolute difference greater than 10% between baseline and post-treatment platelet aggregation (maximum extent) with 20 μM ADP used as the agonist	patients with an absolute difference greater than 10% between baseline and post-treatment platelet aggregation (maximum extent) with 20 μM ADP used as the agonist
Measure Participants	14	13
Least Squares Mean (95% Confidence Interval) [Percent]	95.0	48.5

6. Secondary Outcome

Title	Clopidogrel Responders Final Extent IPA Post Switching Treatment - Comparing Clopidogrel to Clopidogrel Versus Clopidogrel to Ticagrelor on Day 28
Description	IPA(%)=(PAb-PAt)/PAb*100. PA (platelet aggregation) is measured by LTA (Light Transmittance Aggregometry). PAb is the response at baseline (last measurement before study drug) and PAt is a response at post-treatment. IPA=0% means no PA inhibition and 100% means 100% PA inhibition. Please refer to the protocol section for details about the interventions administered.
Time Frame	4 hrs post first dose on day 28

Outcome Measure Data

Analysis Population Description

Intent-to-treat analysis set: included patients who were assigned to a cohort, randomised to a treatment group, received at least one dose of study drug, and contributed post baseline data.

Arm/Group Title	Responder: Ticagrelor	Responder: Clopidogrel
Arm/Group Description	patients with an absolute difference greater than 10% between baseline and post-treatment platelet aggregation (maximum extent) with 20 μM ADP used as the agonist	patients with an absolute difference greater than 10% between baseline and post-treatment platelet aggregation (maximum extent) with 20 μM ADP used as the agonist
Measure Participants	14	13
Least Squares Mean (95% Confidence Interval) [Percent]	77.4	60.8

Adverse Events

Time Frame	Switching Period - first 24 hrs (Day 15), patients switched study medication (from clop. to ticag. or vice versa). Non-Switching Period - Day 1-14 and Day 16-28.
Adverse Event Reporting Description	Analysis included all randomized subjects.
Arm/Group Title	Clopidogrel Non-Responders/Non-Switching Period: Ticagrelor		Clopidogrel Non-Responders/Non-Switching Period: Clopidogrel		Clop. Non-Responders/Switching Period:Ticagrelor-Clopidogrel		Clop. Non-Responders/Switching Period: Clopidogrel-Ticagrelor		Clop. Responders/Non-Switching Period: Ticagrelor		Clop. Responders/Non-Switching Period: Clopidogrel		Clop. Responders/Switching Period: Ticagrelor-Clopidogrel		Clop. Responders/Switching Period: Clopidogrel-Ticagrelor
Arm/Group Description	included non-responders exposed to ticagrelor on Day 1-14, Day 16-28.		included non-responders exposed to clopidogrel on Day 1-14, Day 16-28.		included non-responders exposed to ticagrelor switching to clopidogrel on Day 15.		included non-responders exposed to clopidogrel switching to ticagrelor on Day 15.		included responders exposed to ticagrelor on Day 1-14, Day 16-28.		included responders exposed to clopidogrel on Day 1-14, Day 16-28.		included responders exposed to ticagrelor switching to clopidogrel on Day 15.		included responders exposed to clopidogrel switching to ticagrelor on Day 15.
All Cause Mortality
	Clopidogrel Non-Responders/Non-Switching Period: Ticagrelor		Clopidogrel Non-Responders/Non-Switching Period: Clopidogrel		Clop. Non-Responders/Switching Period:Ticagrelor-Clopidogrel		Clop. Non-Responders/Switching Period: Clopidogrel-Ticagrelor		Clop. Responders/Non-Switching Period: Ticagrelor		Clop. Responders/Non-Switching Period: Clopidogrel		Clop. Responders/Switching Period: Ticagrelor-Clopidogrel		Clop. Responders/Switching Period: Clopidogrel-Ticagrelor
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Clopidogrel Non-Responders/Non-Switching Period: Ticagrelor		Clopidogrel Non-Responders/Non-Switching Period: Clopidogrel		Clop. Non-Responders/Switching Period:Ticagrelor-Clopidogrel		Clop. Non-Responders/Switching Period: Clopidogrel-Ticagrelor		Clop. Responders/Non-Switching Period: Ticagrelor		Clop. Responders/Non-Switching Period: Clopidogrel		Clop. Responders/Switching Period: Ticagrelor-Clopidogrel		Clop. Responders/Switching Period: Clopidogrel-Ticagrelor
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/39 (5.1%)		0/38 (0%)		0/18 (0%)		0/18 (0%)		2/44 (4.5%)		0/42 (0%)		0/13 (0%)		0/16 (0%)
Cardiac disorders
Atrial Fibrillation	0/39 (0%)		0/38 (0%)		0/18 (0%)		0/18 (0%)		1/44 (2.3%)		0/42 (0%)		0/13 (0%)		0/16 (0%)
Bradycardia	0/39 (0%)		0/38 (0%)		0/18 (0%)		0/18 (0%)		1/44 (2.3%)		0/42 (0%)		0/13 (0%)		0/16 (0%)
Myocardial Infarction	1/39 (2.6%)		0/38 (0%)		0/18 (0%)		0/18 (0%)		0/44 (0%)		0/42 (0%)		0/13 (0%)		0/16 (0%)
Ventricular Extrasystoles	0/39 (0%)		0/38 (0%)		0/18 (0%)		0/18 (0%)		1/44 (2.3%)		0/42 (0%)		0/13 (0%)		0/16 (0%)
Vascular disorders
Hypotension	1/39 (2.6%)		0/38 (0%)		0/18 (0%)		0/18 (0%)		0/44 (0%)		0/42 (0%)		0/13 (0%)		0/16 (0%)
Other (Not Including Serious) Adverse Events
	Clopidogrel Non-Responders/Non-Switching Period: Ticagrelor		Clopidogrel Non-Responders/Non-Switching Period: Clopidogrel		Clop. Non-Responders/Switching Period:Ticagrelor-Clopidogrel		Clop. Non-Responders/Switching Period: Clopidogrel-Ticagrelor		Clop. Responders/Non-Switching Period: Ticagrelor		Clop. Responders/Non-Switching Period: Clopidogrel		Clop. Responders/Switching Period: Ticagrelor-Clopidogrel		Clop. Responders/Switching Period: Clopidogrel-Ticagrelor
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	13/39 (33.3%)		13/39 (33.3%)		1/18 (5.6%)		4/18 (22.2%)		19/44 (43.2%)		14/42 (33.3%)		2/13 (15.4%)		1/16 (6.3%)
Gastrointestinal disorders
DYSPEPSIA	0/39 (0%)		0/38 (0%)		0/18 (0%)		0/18 (0%)		1/44 (2.3%)		4/42 (9.5%)		0/13 (0%)		0/16 (0%)
NAUSEA	0/39 (0%)		1/38 (2.6%)		0/18 (0%)		0/18 (0%)		0/44 (0%)		4/42 (9.5%)		0/13 (0%)		0/16 (0%)
DIARRHOEA	2/39 (5.1%)		1/38 (2.6%)		0/18 (0%)		0/18 (0%)		1/44 (2.3%)		2/42 (4.8%)		0/13 (0%)		0/16 (0%)
General disorders
FATIGUE	0/39 (0%)		1/38 (2.6%)		0/18 (0%)		0/18 (0%)		1/44 (2.3%)		2/42 (4.8%)		1/13 (7.7%)		0/16 (0%)
VESSEL PUNCTURE SITE HAEMATOMA	0/39 (0%)		0/38 (0%)		0/18 (0%)		1/18 (5.6%)		2/44 (4.5%)		2/42 (4.8%)		0/13 (0%)		0/16 (0%)
CHEST DISCOMFORT	0/39 (0%)		0/38 (0%)		1/18 (5.6%)		0/18 (0%)		0/44 (0%)		0/42 (0%)		0/13 (0%)		0/16 (0%)
Injury, poisoning and procedural complications
CONTUSION	0/39 (0%)		0/38 (0%)		0/18 (0%)		0/18 (0%)		3/44 (6.8%)		0/42 (0%)		0/13 (0%)		0/16 (0%)
TRAUMATIC HAEMATOMA	0/39 (0%)		2/38 (5.3%)		0/18 (0%)		0/18 (0%)		2/44 (4.5%)		0/42 (0%)		0/13 (0%)		0/16 (0%)
Musculoskeletal and connective tissue disorders
ARTHRALGIA	0/39 (0%)		0/38 (0%)		0/18 (0%)		0/18 (0%)		0/44 (0%)		1/42 (2.4%)		1/13 (7.7%)		0/16 (0%)
MYALGIA	0/39 (0%)		1/38 (2.6%)		0/18 (0%)		0/18 (0%)		0/44 (0%)		0/42 (0%)		1/13 (7.7%)		0/16 (0%)
Nervous system disorders
DIZZINESS	1/39 (2.6%)		3/38 (7.9%)		0/18 (0%)		2/18 (11.1%)		1/44 (2.3%)		1/42 (2.4%)		0/13 (0%)		0/16 (0%)
HEADACHE	2/39 (5.1%)		1/38 (2.6%)		0/18 (0%)		0/18 (0%)		0/44 (0%)		1/42 (2.4%)		0/13 (0%)		0/16 (0%)
PARAESTHESIA	0/39 (0%)		2/38 (5.3%)		0/18 (0%)		0/18 (0%)		1/44 (2.3%)		0/42 (0%)		0/13 (0%)		0/16 (0%)
RESTLESS LEGS SYNDROME	0/39 (0%)		1/38 (2.6%)		0/18 (0%)		1/18 (5.6%)		0/44 (0%)		0/42 (0%)		0/13 (0%)		0/16 (0%)
Respiratory, thoracic and mediastinal disorders
DYSPNOEA	7/39 (17.9%)		3/38 (7.9%)		1/18 (5.6%)		2/18 (11.1%)		6/44 (13.6%)		0/42 (0%)		0/13 (0%)		0/16 (0%)
EPISTAXIS	0/39 (0%)		0/38 (0%)		0/18 (0%)		0/18 (0%)		3/44 (6.8%)		0/42 (0%)		0/13 (0%)		0/16 (0%)
Skin and subcutaneous tissue disorders
INCREASED TENDENCY TO BRUISE	3/39 (7.7%)		1/38 (2.6%)		0/18 (0%)		0/18 (0%)		2/44 (4.5%)		2/42 (4.8%)		0/13 (0%)		1/16 (6.3%)

Limitations/Caveats

[Not Specified]

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Certain Agreements

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

An Investigator agrees to provide a copy of the publication to AZ for review at least 60 days in advance of submission for publication. Investigators in multicenter (MC) studies agree to postpone MC publications until the earlier of the date of the first AZ-authorized MC publication or a period up to 18 months from study completion at all sites.