A Comparison of Prasugrel and Clopidogrel in Acute Coronary Syndrome Subjects (TRILOGY ACS)

• ClinicalTrials.gov Identifier: NCT00699998
• Recruitment Status: Completed
• First Posted: June 18, 2008
• Results First Posted: May 7, 2013
• Last Update Posted: May 7, 2013
• Sponsor: Eli Lilly and Company
• Collaborators: Daiichi Sankyo Co., Ltd.; Duke Clinical Research Institute
• Information provided by (Responsible Party): Eli Lilly and Company

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Acute Coronary Syndrome
• Interventions: Drug: Clopidogrel; Drug: Prasugrel; Drug: Commercially-available Aspirin
• Enrollment: 9326

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Prasugrel: <75 Years of Age	Prasugrel: 75 Years of Age or Older	Clopidogrel: <75 Years of Age	Clopidogrel: 75 Years of Age or Older
Arm/Group Description	Prasugrel and Low-dose Commercially-available Aspirin in participants less than (<) 75 years of age. Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study. Prasugrel: 30 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and either 5 mg or 10 mg (based upon weight) orally, once daily as maintenance dose through end of study.	Prasugrel and Low-dose Commercially-available Aspirin in participants 75 years of age or older. Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study. Prasugrel: 30 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and 5 mg orally, once daily as maintenance dose through end of study.	Clopidogrel and Low-Dose Commercially-available Aspirin in participants less than (<) 75 years of age. Commercially-available Aspirin : Low-dose aspirin, oral, as prescribed by physician through end of study Clopidogrel: 300 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and 75 mg, oral, once daily as maintenance dose through end of study	Clopidogrel and Low-Dose Commercially-available Aspirin in participants 75 years of age or older. Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study. Clopidogrel: 300 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and 75 mg, oral, once daily as maintenance dose through end of study.
Period Title: Overall Study
Started	3620	1043	3623	1040
Received at Least 1 Dose of Study Drug	3590	1033	3590	1027
Completed	3421	957	3417	958
Not Completed	199	86	206	82
Reason Not Completed
Withdrawal by Subject	194	83	202	80
Physician Decision	3	2	1	1
Lost to Follow-up	2	1	3	1

Baseline Characteristics

Arm/Group Title		Prasugrel: <75 Years of Age	Prasugrel: 75 Years of Age or Older	Clopidogrel: <75 Years of Age	Clopidogrel: 75 Years of Age or Older	Total
Arm/Group Description		Prasugrel and Low-dose Commercially-available Aspirin in participants less than (<) 75 years of age. Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study. Prasugrel : 30 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and either 5 mg or 10 mg (based upon weight) orally, once daily as maintenance dose through end of study.	Prasugrel and Low-dose Commercially-available Aspirin in participants 75 years of age or older. Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study. Prasugrel: 30 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and 5 mg orally, once daily as maintenance dose through end of study.	Clopidogrel and Low-Dose Commercially-available Aspirin in participants less than (<) 75 years of age. Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study. Clopidogrel: 300 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and 75 mg, oral, once daily as maintenance dose through end of study.	Clopidogrel and Low-Dose Commercially-available Aspirin in participants 75 years of age or older. Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study. Clopidogrel: 300 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and 75 mg, oral, once daily as maintenance dose through end of study.	Total of all reporting groups
Overall Number of Baseline Participants		3620	1043	3623	1040	9326
Baseline Analysis Population Description		[Not Specified]
Age Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	3620 participants	1043 participants	3623 participants	1040 participants	9326 participants
		61.4 (8.55)	80.3 (4.29)	61.5 (8.38)	80.3 (4.39)	65.7 (11.02)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	3620 participants	1043 participants	3623 participants	1040 participants	9326 participants
	Female	1309 36.2%	520 49.9%	1290 35.6%	531 51.1%	3650 39.1%
	Male	2311 63.8%	523 50.1%	2333 64.4%	509 48.9%	5676 60.9%
Race/Ethnicity, Customized; Measure Type: Number; Unit of measure: Participants	Number Analyzed	3620 participants	1043 participants	3623 participants	1040 participants	9326 participants
Caucasian		2362	767	2374	773	6276
African		87	14	72	12	185
Hispanic		321	109	346	86	862
Asian		821	147	800	164	1932
Other		29	6	30	5	70
Unknown		0	0	1	0	1
Region of Enrollment; Measure Type: Number; Unit of measure: Participants	Number Analyzed	3620 participants	1043 participants	3623 participants	1040 participants	9326 participants
Portugal		18	11	14	11	54
Philippines		58	7	48	14	127
Taiwan		6	6	4	9	25
Slovakia		62	20	60	20	162
Greece		14	8	10	11	43
Costa Rica		5	1	2	2	10
Thailand		30	17	36	10	93
Ukraine		326	28	311	42	707
Chile		28	15	33	13	89
Italy		71	44	70	47	232
India		513	56	508	64	1141
France		29	22	29	19	99
Denmark		21	7	17	10	55
Korea, Republic of		35	7	33	7	82
Panama		29	7	24	10	70
Turkey		76	24	81	19	200
Czech Republic		37	31	32	38	138
Mexico		38	15	40	16	109
Canada		58	14	61	13	146
Brazil		154	27	147	34	362
Romania		103	26	105	23	257
Croatia		63	28	60	31	182
Sweden		4	3	6	1	14
United States		430	133	446	116	1125
Serbia		42	4	40	5	91
Spain		13	8	10	12	43
Ireland		5	4	6	3	18
Israel		75	33	85	21	214
Russian Federation		128	22	135	14	299
Colombia		40	21	45	17	123
Switzerland		6	4	4	6	20
Malaysia		35	7	33	9	84
Peru		58	19	67	12	156
Australia		13	6	15	7	41
South Africa		27	11	27	12	77
Netherlands		55	23	53	24	155
Tunisia		20	3	20	4	47
China		126	38	120	44	328
Finland		3	3	5	2	13
Lithuania		29	8	32	4	73
Austria		6	6	6	5	23
Malta		9	1	10	2	22
United Kingdom		33	21	40	12	106
Egypt		65	1	62	4	132
Hungary		86	43	87	44	260
Argentina		120	58	138	41	357
Poland		137	59	129	68	393
Belgium		7	7	7	8	29
Singapore		2	5	5	1	13
Bulgaria		216	48	209	55	528
Germany		46	20	46	21	133
New Zealand		10	3	10	3	26
History of Diabetes; Measure Type: Number; Unit of measure: Participants	Number Analyzed	3620 participants	1043 participants	3623 participants	1040 participants	9326 participants
Yes		1393	363	1418	365	3539
No		2221	678	2193	675	5767
Unknown		6	2	12	0	20
History of Myocardial Infarction (MI); Measure Type: Number; Unit of measure: Participants	Number Analyzed	3620 participants	1043 participants	3623 participants	1040 participants	9326 participants
Yes		1556	426	1612	393	3987
No		2035	603	1988	633	5259
Unknown		29	14	23	14	80
History of Coronary Revascularization (PCI or CABG) [1]; Measure Type: Number; Unit of measure: Participants	Number Analyzed	3620 participants	1043 participants	3623 participants	1040 participants	9326 participants
Yes		1279	330	1365	299	3273
No		2332	703	2239	734	6008
Unknown		9	10	19	7	45
		[1] Measure Description: History of Coronary Revascularization due to percutaneous coronary intervention (PCI) or coronary artery bypass graft surgery (CABG)
Clinical Presentation of UA or NSTEMI [1]; Measure Type: Number; Unit of measure: Participants	Number Analyzed	3620 participants	1043 participants	3623 participants	1040 participants	9326 participants
Unstable Angina		963	166	981	192	2302
Non-ST-segment Elevation Myocardial Infarction		2453	829	2434	804	6520
Unknown/Did not meet criteria		204	48	208	44	504
		[1] Measure Description: Clinical Presentation of unstable angina (UA) or non-ST-segment elevation myocardial infarction (NSTEMI)

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With a Composite Endpoint of Cardiovascular (CV) Death, Myocardial Infarction (MI), or Stroke
Description	The percentage of participants is the total number of participants experiencing a CV death, nonfatal MI, or nonfatal stroke divided by number of participants in the treatment arm multiplied by 100. Endpoint events were adjudicated by the Clinical Endpoint Committee.
Time Frame	Randomization through end of study (30-month visit)

Outcome Measure Data

Analysis Population Description

All randomized participants

Arm/Group Title	Prasugrel: <75 Years of Age	Prasugrel: 75 Years of Age or Older	Clopidogrel: <75 Years of Age	Clopidogrel: 75 Years of Age or Older
Arm/Group Description:	Prasugrel and Low-dose Commercially-available Aspirin in participants less than (<) 75 years of age. Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study Prasugrel: 30 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and either 5 mg or 10 mg (based upon weight) orally, once daily as maintenance dose through end of study.	Prasugrel and Low-dose Commercially-available Aspirin in participants 75 years of age or older. Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study. Prasugrel: 30 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and 5 mg orally, once daily as maintenance dose through end of study.	Clopidogrel and Low-Dose Commercially-available Aspirin in participants less than (<) 75 years of age. Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study. Clopidogrel: 300 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and 75 mg, oral, once daily as maintenance dose through end of study.	Clopidogrel and Low-Dose Commercially-available Aspirin in participants 75 years of age or older. Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study. Clopidogrel: 300 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and 75 mg, oral, once daily as maintenance dose through end of study.
Overall Number of Participants Analyzed	3620	1043	3623	1040
Measure Type: Number; Unit of Measure: percentage of participants with an event
	10.06	24.64	10.96	24.13

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Prasugrel: <75 Years of Age, Clopidogrel: <75 Years of Age
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.210
	Comments	Two-sided p-value based on a log-rank test stratified by clopidogrel status at randomization.
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.915
	Confidence Interval	(2-Sided) 95%; 0.793 to 1.055
	Estimation Comments	HR and two-sided 95% CI derived using Cox proportional hazards model with treatment and clopidogrel status at randomization as fixed effects.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Prasugrel: 75 Years of Age or Older, Clopidogrel: 75 Years of Age or Older
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.731
	Comments	Two-sided p-value based on a log-rank test stratified by clopidogrel status at randomization.
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.029
	Confidence Interval	(2-Sided) 95%; 0.865 to 1.225
	Estimation Comments	HR and two-sided 95% CI derived using Cox proportional hazards model with treatment and clopidogrel status at randomization as fixed effects.

2. Secondary Outcome

Title	Percentage of Participants With a Composite Endpoint of CV Death and MI
Description	The percentage of participants is the total number of participants experiencing a CV death or nonfatal MI divided by number of participants in the treatment arm. Endpoint events were adjudicated by the Clinical Endpoint Committee.
Time Frame	Randomization through end of study (30-month visit)

Outcome Measure Data

Analysis Population Description

All randomized participants

Arm/Group Title	Prasugrel: <75 Years of Age	Prasugrel: 75 Years of Age or Older	Clopidogrel: <75 Years of Age	Clopidogrel: 75 Years of Age or Older
Arm/Group Description:	Prasugrel and Low-dose Commercially-available Aspirin in participants less than (<) 75 years of age. Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study. Prasugrel: 30 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and either 5 mg or 10 mg (based upon weight) orally, once daily as maintenance dose through end of study.	Prasugrel and Low-dose Commercially-available Aspirin in participants 75 years of age or older. Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study. Prasugrel: 30 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and 5 mg orally, once daily as maintenance dose through end of study.	Clopidogrel and Low-Dose Commercially-available Aspirin in participants less than (<) 75 years of age. Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study. Clopidogrel: 300 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and 75 mg, oral, once daily as maintenance dose through end of study.	Clopidogrel and Low-Dose Commercially-available Aspirin in participants 75 years of age or older. Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study. Clopidogrel: 300 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and 75 mg, oral, once daily as maintenance dose through end of study.
Overall Number of Participants Analyzed	3620	1043	3623	1040
Measure Type: Number; Unit of Measure: percentage of participants with an event
	9.61	22.53	10.21	22.69

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Prasugrel: <75 Years of Age, Clopidogrel: <75 Years of Age
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.388
	Comments	[Not Specified]
	Method	Log Rank
	Comments	Two-sided p-value based on a log-rank test stratified by clopidogrel status at randomization.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.940
	Confidence Interval	(2-Sided) 95%; 0.812 to 1.088
	Estimation Comments	HR and two-sided 95% CI derived using Cox proportional hazards model with treatment and clopidogrel status at randomization as fixed effects.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Prasugrel: 75 Years of Age or Older, Clopidogrel: 75 Years of Age or Older
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.990
	Comments	Two-sided p-value based on a log-rank test stratified by clopidogrel status at randomization.
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.998
	Confidence Interval	(2-Sided) 95%; 0.833 to 1.195
	Estimation Comments	HR and two-sided 95% CI derived using Cox proportional hazards model with treatment and clopidogrel status at randomization as fixed effects.

3. Secondary Outcome

Title	Percentage of Participants With a Composite Endpoint of CV Death, MI, Stroke, or Re-hospitalization for Recurrent Unstable Angina (UA)
Description	The percentage of participants is the total number of participants experiencing a CV death, nonfatal MI, nonfatal stroke or re-hospitalization for a recurrent UA divided by number of participants in the treatment arm. Endpoints events were adjudicated by the Clinical Endpoint Committee.
Time Frame	Randomization through end of study (30-month visit)

Outcome Measure Data

Analysis Population Description

All randomized participants

Arm/Group Title	Prasugrel: <75 Years of Age	Prasugrel: 75 Years of Age or Older	Clopidogrel: <75 Years of Age	Clopidogrel: 75 Years of Age or Older
Arm/Group Description:	Prasugrel and Low-dose Commercially-available Aspirin in participants less than (<) 75 years of age. Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study. Prasugrel: 30 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and either 5 mg or 10 mg (based upon weight) orally, once daily as maintenance dose through end of study.	Prasugrel and Low-dose Commercially-available Aspirin in participants 75 years of age or older. Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study. Prasugrel: 30 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and 5 mg orally, once daily as maintenance dose through end of study.	Clopidogrel and Low-Dose Commercially-available Aspirin in participants less than (<) 75 years of age. Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study. Clopidogrel: 300 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and 75 mg, oral, once daily as maintenance dose through end of study.	Clopidogrel and Low-Dose Commercially-available Aspirin in participants 75 years of age or older. Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study. Clopidogrel: 300 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and 75 mg, oral, once daily as maintenance dose through end of study.
Overall Number of Participants Analyzed	3620	1043	3623	1040
Measure Type: Number; Unit of Measure: percentage of participants with an event
	12.13	26.27	12.83	25.67

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Prasugrel: <75 Years of Age, Clopidogrel: <75 Years of Age
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.353
	Comments	Two-sided p-value based on a log-rank test stratified by clopidogrel status at randomization.
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.941
	Confidence Interval	(2-Sided) 95%; 0.826 to 1.073
	Estimation Comments	HR and two-sided 95% CI derived using Cox proportional hazards model with treatment and clopidogrel status at randomization as fixed effects.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Prasugrel: 75 Years of Age or Older, Clopidogrel: 75 Years of Age or Older
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.719
	Comments	Two-sided p-value based on a log-rank test stratified by clopidogrel status at randomization.
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.029
	Confidence Interval	(2-Sided) 95%; 0.869 to 1.218
	Estimation Comments	HR and two-sided 95% CI derived using Cox proportional hazards model with treatment and clopidogrel status at randomization as fixed effects.

4. Secondary Outcome

Title	Percentage of Participants With a Composite Endpoint of All-cause Death, MI, or Stroke
Description	The percentage of participants is the total number of participants experiencing an all-cause death, nonfatal MI, or nonfatal stroke divided by number of participants in the treatment arm. Endpoint events were adjudicated by the Clinical Endpoint Committee.
Time Frame	Randomization through end of study (30-month visit)

Outcome Measure Data

Analysis Population Description

All randomized participants

Arm/Group Title	Prasugrel: <75 Years of Age	Prasugrel: 75 Years of Age or Older	Clopidogrel: <75 Years of Age	Clopidogrel: 75 Years of Age or Older
Arm/Group Description:	Prasugrel and Low-dose Commercially-available Aspirin in participants less than (<) 75 years of age. Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study. Prasugrel: 30 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and either 5 mg or 10 mg (based upon weight) orally, once daily as maintenance dose through end of study.	Prasugrel and Low-dose Commercially-available Aspirin in participants 75 years of age or older. Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study. Prasugrel: 30 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and 5 mg orally, once daily as maintenance dose through end of study.	Clopidogrel and Low-Dose Commercially-available Aspirin in participants less than (<) 75 years of age. Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study. Clopidogrel: 300 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and 75 mg, oral, once daily as maintenance dose through end of study.	Clopidogrel and Low-Dose Commercially-available Aspirin in participants 75 years of age or older. Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study. Clopidogrel: 300 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and 75 mg, oral, once daily as maintenance dose through end of study.
Overall Number of Participants Analyzed	3620	1043	3623	1040
Measure Type: Number; Unit of Measure: percentage of participants with an event
	10.61	27.04	11.12	26.83

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Prasugrel: <75 Years of Age, Clopidogrel: <75 Years of Age
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.270
	Comments	Two-sided p-value based on a log-rank test stratified by clopidogrel status at randomization.
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.928
	Confidence Interval	(2-Sided) 95%; 0.810 to 1.063
	Estimation Comments	HR and two-sided 95% CI derived using Cox proportional hazards model with treatment and clopidogrel status at randomization as fixed effects.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Prasugrel: 75 Years of Age or Older, Clopidogrel: 75 Years of Age or Older
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.831
	Comments	Two-sided p-value based on a log-rank test stratified by clopidogrel status at randomization.
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.017
	Confidence Interval	(2-Sided) 95%; 0.862 to 1.200
	Estimation Comments	HR and two-sided 95% CI derived using Cox proportional hazards model with treatment and clopidogrel status at randomization as fixed effects.

5. Secondary Outcome

Title	Platelet Aggregation Measures
Description	Platelet aggregation was measured by as measured by Accumetrics Verify Now™ P2Y12. Results were reported in P2Y12 Reaction Units (PRU). PRU represents the rate and extent of adenosine (ADP)-stimulated platelet aggregation. Lower values indicate greater P2Y12 platelet inhibition and lower platelet activity and aggregation. ANCOVA Model was used and values were corrected for treatment + baseline value + clopidogrel status at randomization.
Time Frame	Day 30 and 12 Months

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of study drug, and had a baseline and post-baseline PRU measurement at Day 30 or Month 12.

Arm/Group Title	Prasugrel: <75 Years of Age	Prasugrel: 75 Years of Age or Older	Clopidogrel: <75 Years of Age	Clopidogrel: 75 Years of Age or Older
Arm/Group Description:	Prasugrel and Low-dose Commercially-available Aspirin in participants less than (<) 75 years of age. Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study. Prasugrel: 30 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and either 5 mg or 10 mg (based upon weight) orally, once daily as maintenance dose through end of study.	Prasugrel and Low-dose Commercially-available Aspirin in participants 75 years of age or older. Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study. Prasugrel: 30 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and 5 mg orally, once daily as maintenance dose through end of study.	Clopidogrel and Low-Dose Commercially-available Aspirin in participants less than (<) 75 years of age. Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study. Clopidogrel: 300 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and 75 mg, oral, once daily as maintenance dose through end of study.	Clopidogrel and Low-Dose Commercially-available Aspirin in participants 75 years of age or older. Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study. Clopidogrel: 300 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and 75 mg, oral, once daily as maintenance dose through end of study.
Overall Number of Participants Analyzed	720	158	683	179
Least Squares Mean (Standard Error); Unit of Measure: P2Y12 Reaction Units (PRU)
Day 30	93.280 (3.804)	151.872 (8.148)	193.489 (3.780)	200.285 (8.238)
Month 12 (n=386, 76, 400, 103)	94.529 (5.706)	135.096 (14.631)	199.003 (5.663)	181.360 (14.380)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Prasugrel: <75 Years of Age, Clopidogrel: <75 Years of Age
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	p-value is for Day 30 comparison. ANCOVA Model: Measurement = treatment + baseline value + clopidogrel status at randomization.
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-100.208
	Confidence Interval	(2-Sided) 95%; -107.872 to -92.545
	Estimation Comments	Estimated Mean Difference (Final Values) for Day 30 comparison

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Prasugrel: <75 Years of Age, Clopidogrel: <75 Years of Age
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	p-value is for 12 month comparison. ANCOVA Model: Measurement = treatment + baseline value + clopidogrel status at randomization.
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-104.475
	Confidence Interval	(2-Sided) 95%; -115.383 to -93.566
	Estimation Comments	Estimated Mean Difference (Final Values) for 12 month comparison.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Prasugrel: 75 Years of Age or Older, Clopidogrel: 75 Years of Age or Older
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	p-value is for 30 day comparison. ANCOVA Model: Measurement = treatment + baseline value + clopidogrel status at randomization.
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-48.413
	Confidence Interval	(2-Sided) 95%; -63.718 to -33.108
	Estimation Comments	Estimated Mean Difference (Final Values) is for the 30 day comparison.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Prasugrel: 75 Years of Age or Older, Clopidogrel: 75 Years of Age or Older
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	p-value is for the 12 month comparison. ANCOVA Model: Measurement = treatment + baseline value + clopidogrel status at randomization.
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-46.264
	Confidence Interval	(2-Sided) 95%; -69.061 to -23.468
	Estimation Comments	Estimated Mean Difference (Final Values) is for the 12 month comparison.

6. Secondary Outcome

Title	Biomarker Measurements of Inflammation/Hemodynamic Stress: Brain Natriuretic Peptide (BNP)
Description	Brain natriuretic peptide (BNP) is secreted by the ventricles of the heart in response to hemodynamic stress and is a biomarker associated with increased CV risk. Results are presented as geometric least squares means (Geometric LS means). Geometric LS means were adjusted for treatment + baseline value + clopidogrel status at randomization.
Time Frame	Day 30 and 6 Months

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study therapy and had baseline and post-baseline BNP measurement at Day 30 or 6 Months.

Arm/Group Title	Prasugrel: <75 Years of Age	Prasugrel: 75 Years of Age or Older	Clopidogrel: <75 Years of Age	Clopidogrel: 75 Years of Age or Older
Arm/Group Description:	Prasugrel and Low-dose Commercially-available Aspirin in participants less than (<) 75 years of age. Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study. Prasugrel: 30 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and either 5 mg or 10 mg (based upon weight) orally, once daily as maintenance dose through end of study.	Prasugrel and Low-dose Commercially-available Aspirin in participants 75 years of age or older. Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study. Prasugrel: 30 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and 5 mg orally, once daily as maintenance dose through end of study.	Clopidogrel and Low-Dose Commercially-available Aspirin in participants less than (<) 75 years of age. Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study. Clopidogrel: 300 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and 75 mg, oral, once daily as maintenance dose through end of study.	Clopidogrel and Low-Dose Commercially-available Aspirin in participants 75 years of age or older. Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study. Clopidogrel: 300 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and 75 mg, oral, once daily as maintenance dose through end of study.
Overall Number of Participants Analyzed	859	196	840	224
Geometric Mean (Standard Error); Unit of Measure: picograms per milliliter (pg/mL)
Day 30	313.494 (1.039)	1082.396 (1.093)	319.345 (1.039)	951.359 (1.092)
6 Months (n=725, 125, 701, 174)	253.434 (1.049)	770.132 (1.135)	250.982 (1.049)	722.750 (1.130)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Prasugrel: <75 Years of Age, Clopidogrel: <75 Years of Age
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.631
	Comments	p-value is for the 30 day comparison. ANCOVA Model: Measurement = treatment + baseline value + clopidogrel status at randomization.
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Geometric Ratio Estimate
	Estimated Value	0.982
	Confidence Interval	(2-Sided) 95%; 0.910 to 1.059
	Estimation Comments	Geometric Ratio Estimate is for the 30 day comparison.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Prasugrel: <75 Years of Age, Clopidogrel: <75 Years of Age
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.844
	Comments	p-value is for the 6 month comparison. ANCOVA Model: Measurement = treatment + baseline value + clopidogrel status at randomization.
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Geometric Ratio Estimate
	Estimated Value	1.010
	Confidence Interval	(2-Sided) 95%; 0.916 to 1.113
	Estimation Comments	Geometric Ratio Estimate is for the 6 month comparison.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Prasugrel: 75 Years of Age or Older, Clopidogrel: 75 Years of Age or Older
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.098
	Comments	p-value is for the 30 day comparison. ANCOVA Model: Measurement = treatment + baseline value + clopidogrel status at randomization.
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Geometric Ratio Estimate
	Estimated Value	1.138
	Confidence Interval	(2-Sided) 95%; 0.977 to 1.325
	Estimation Comments	Geometric Ratio Estimate is for the 30 day comparison.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Prasugrel: 75 Years of Age or Older, Clopidogrel: 75 Years of Age or Older
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.545
	Comments	p-value is for the 6 month comparison. ANCOVA Model: Measurement = treatment + baseline value + clopidogrel status at randomization.
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Geometric Ratio Estimate
	Estimated Value	1.066
	Confidence Interval	(2-Sided) 95%; 0.867 to 1.310
	Estimation Comments	Geometric Ratio Estimate is for the 6 month comparison.

7. Secondary Outcome

Title	Biomarker Measurements of Inflammation/Hemodynamic Stress: C-Reactive Protein (CRP)
Description	C-Reactive Protein (CRP) is a biomarker associated with inflammation and increased CV risk. Results are presented as geometric least squares means (Geometric LS means). Geometric LS means were adjusted for treatment + baseline value + clopidogrel status at randomization.
Time Frame	Day 30 and Month 6

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study therapy and had baseline and post-baseline CRP measurement at Day 30 or 6 Months.

Arm/Group Title	Prasugrel: <75 Years of Age	Prasugrel: 75 Years of Age or Older	Clopidogrel: <75 Years of Age	Clopidogrel: 75 Years of Age or Older
Arm/Group Description:	Prasugrel and Low-dose Commercially-available Aspirin in participants less than (<) 75 years of age. Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study Prasugrel: 30 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and either 5 mg or 10 mg (based upon weight) orally, once daily as maintenance dose through end of study.	Prasugrel and Low-dose Commercially-available Aspirin in participants 75 years of age or older. Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study. Prasugrel: 30 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and 5 mg orally, once daily as maintenance dose through end of study.	Clopidogrel and Low-Dose Commercially-available Aspirin in participants less than (<) 75 years of age. Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study. Clopidogrel: 300 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and 75 mg, oral, once daily as maintenance dose through end of study.	Clopidogrel and Low-Dose Commercially-available Aspirin in participants 75 years of age or older. Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study. Clopidogrel: 300 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and 75 mg, oral, once daily as maintenance dose through end of study.
Overall Number of Participants Analyzed	888	209	863	226
Geometric Mean (Standard Error); Unit of Measure: milligrams per liter (mg/L)
Day 30	2.330 (1.053)	2.441 (1.150)	2.287 (1.053)	2.226 (1.150)
6 Months (n=755, 143, 745, 178)	2.272 (1.060)	1.593 (1.173)	2.149 (1.059)	1.543 (1.170)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Prasugrel: <75 Years of Age, Clopidogrel: <75 Years of Age
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.727
	Comments	p-value is for the 30 day comparison. ANCOVA Model: Measurement = treatment + baseline value + clopidogrel status at randomization.
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Geometric Ratio Estimate
	Estimated Value	1.018
	Confidence Interval	(2-Sided) 95%; 0.919 to 1.129
	Estimation Comments	Geometric Ratio Estimate is for the 30 day comparison.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Prasugrel: <75 Years of Age, Clopidogrel: <75 Years of Age
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.346
	Comments	p-value is for the 6 month comparison. ANCOVA Model: Measurement = treatment + baseline value + clopidogrel status at randomization.
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Geometric Ratio Estimate
	Estimated Value	1.057
	Confidence Interval	(2-Sided) 95%; 0.942 to 1.187
	Estimation Comments	Geometric Ratio Estimate is for the 6 month comparison.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Prasugrel: 75 Years of Age or Older, Clopidogrel: 75 Years of Age or Older
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.458
	Comments	p-value is for the 30 day comparison. ANCOVA Model: Measurement = treatment + baseline value + clopidogrel status at randomization.
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Geometric Ratio Estimate
	Estimated Value	1.096
	Confidence Interval	(2-Sided) 95%; 0.859 to 1.399
	Estimation Comments	Geometric Ratio Estimate is for the 30 day comparison.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Prasugrel: 75 Years of Age or Older, Clopidogrel: 75 Years of Age or Older
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.802
	Comments	p-value is for the 6 month comparison. ANCOVA Model: Measurement = treatment + baseline value + clopidogrel status at randomization.
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Geometric Ratio Estimate
	Estimated Value	1.033
	Confidence Interval	(2-Sided) 95%; 0.803 to 1.329
	Estimation Comments	Geometric Ratio Estimate is for the 6 month comparison.

8. Secondary Outcome

Title	Genotyping Related to Drug Metabolism
Description	Variation in the genes encoding the cytochrome P450 (CYP) enzymes (CYP2C19) can reduce the ability to metabolize clopidogrel and a reduced platelet response and have been associated with increased rates of CV events including CV death. Participants were classified as extensive metabolizers (EM); reduced metabolizers (RM); or unknown (UNK) metabolizers based on their CYP2C19 genotype. Possible extensive metabolizer (EM) phenotypes include EM=extensive metabolizer, UM=ultra-rapid metabolizer, and EM (non-UM) that are not UM. Possible reduced metabolizer (RM) phenotypes include IM=intermediate metabolizer and PM=poor metabolizer. Genotypes associated with each predicted phenotype are presented; predicted phenotype is presented first followed by the genotype. Percentage=(number of participants with the predicted phenotype and genotype divided by the total number of participants per arm) multiplied by 100.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

All randomized participants who provided a DNA sample.

Arm/Group Title	Prasugrel: <75 Years of Age	Prasugrel: 75 Years of Age or Older	Clopidogrel: <75 Years of Age	Clopidogrel: 75 Years of Age or Older
Arm/Group Description:	Prasugrel and Low-dose Commercially-available Aspirin in participants less than (<) 75 years of age. Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study Prasugrel: 30 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and either 5 mg or 10 mg (based upon weight) orally, once daily as maintenance dose through end of study.	Prasugrel and Low-dose Commercially-available Aspirin in participants 75 years of age or older. Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study. Prasugrel: 30 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and 5 mg orally, once daily as maintenance dose through end of study.	Clopidogrel and Low-Dose Commercially-available Aspirin in participants less than (<) 75 years of age. Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study. Clopidogrel: 300 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and 75 mg, oral, once daily as maintenance dose through end of study.	Clopidogrel and Low-Dose Commercially-available Aspirin in participants 75 years of age or older. Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study. Clopidogrel: 300 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and 75 mg, oral, once daily as maintenance dose through end of study.
Overall Number of Participants Analyzed	2210	639	2237	650
Measure Type: Number; Unit of Measure: percentage participants with geneotype
UM, *1/*17	24.0	25.0	25.1	21.8
UM, *17/*17	5.1	3.6	5.4	4.3
EM (non-UM), *1/*1	38.8	42.1	35.7	41.2
IM, *1/*2	18.6	18.3	19.8	19.7
IM, *1/*3	0.8	0.6	0.5	0.6
IM, *1/*4	0.4	0.0	0.1	0.3
IM, *1/*6	0.0	0.2	0.0	0.2
IM, *1/*8	0.1	0.5	0.4	0.3
PM, *2/*2	3.9	2.2	4.3	3.8
PM, *2/*3	0.3	0.2	0.3	0.3
PM, *2/*4	0.0	0.2	0.2	0.2
PM, *2/*6	0.0	0.0	0.0	0.0
PM, *2/*8	0.0	0.0	0.0	0.0
PM, *3/*3	0.0	0.0	0.2	0.0
UNK, *1/*10	0.0	0.0	0.1	0.0
UNK, *1/*13	0.0	0.2	0.0	0.0
UNK, *1/*9	0.1	0.2	0.0	0.0
UNK, *1/*9, *9/*17	0.0	0.0	0.0	0.0
UNK, *13/*17	0.0	0.0	0.0	0.0
UNK, *2/*13	0.0	0.0	0.0	0.0
UNK, *2/*17	6.3	6.1	6.8	6.2
UNK, *2/*9	0.0	0.0	0.1	0.0
UNK, *3/*17	0.1	0.0	0.0	0.3
UNK, *4/*17	0.2	0.2	0.2	0.0
UNK, *4/*9	0.0	0.0	0.0	0.0
UNK, *6/*17	0.0	0.0	0.0	0.2
UNK, *8/*17	0.2	0.0	0.1	0.0
UNK, *9/*17	0.0	0.0	0.0	0.0
UNK, Undefined genotype	0.7	0.6	0.5	0.6

9. Secondary Outcome

Title	Economic and Quality of Life Outcomes
Description	Seattle Angina Questionnaire (SAQ) is a validated, disease-specific questionnaire containing 11 questions (Q) yielding 5 summary scales related to angina: physical limitations, angina stability, angina frequency, treatment satisfaction and disease perception. In this study only angina frequency and the physical limitations scales were assessed. Anginal Frequency was assessed using Q3 and Q4 which consists of a Likert scale ranging from 1 to 6 (higher values equals better quality of life) to assess how often a patient is having symptoms now. Physical limitations was assessed using Q1 which contains 9 items each assessed via Likert scale ranging from 1 to 6 (higher values equals better quality of life) to assess how much a participant's condition is hampering their ability to do what they want to do. Scale scores are transformed to a 0-100 by subtracting the lowest possible score, dividing by the range of the scale, and multiplying by 100. Higher values equal better quality of life.
Time Frame	Baseline and follow-up (24 months)

Outcome Measure Data

Analysis Population Description

All randomized participants (combined <75 years and 75 years and older) with SAQ data.

Arm/Group Title	Prasugrel	Clopidogrel
Arm/Group Description:	Prasugrel and Low-dose Commercially-available Aspirin in participants. Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study Prasugrel: 30 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and either 5 mg or 10 mg (based upon weight and age), oral, once daily as maintenance dose through end of study.	Clopidogrel and Low-Dose Commercially-available Aspirin in participants. Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study. Clopidogrel: 300 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and 75 mg, oral, once daily as maintenance dose through end of study.
Overall Number of Participants Analyzed	1506	1506
Mean (Standard Deviation); Unit of Measure: units on a scale
Baseline, physical limitations	67.8 (26.1)	67.0 (26.5)
Baseline, angina frequency	73.6 (22.9)	73.1 (23.5)
24 Months, physical limitations (n=420, 412)	75.1 (24.4)	74.5 (25.7)
24 Months, angina frequency (n=420, 412)	89.7 (20.0)	89.5 (19.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Prasugrel, Clopidogrel
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.5
	Comments	p-value is for the comparison of physical limitations at baseline. p-values are from a regression model with treatment group and the respective baseline quality-of-life measure as predictors.
	Method	ANCOVA
	Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Prasugrel, Clopidogrel
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.72
	Comments	p-value is for the comparison of angina frequency at baseline. p-values are from a regression model with treatment group and the respective baseline quality-of-life measure as predictors.
	Method	ANCOVA
	Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Prasugrel, Clopidogrel
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.63
	Comments	p-value is for the comparison of physical limitations at 24 months. p-values are from a regression model with treatment group and the respective baseline quality-of-life measure as predictors.
	Method	ANCOVA
	Comments	[Not Specified]

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Prasugrel, Clopidogrel
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.53
	Comments	p-value is for the comparison of angina frequency at at 24 months. p-values are from a regression model with treatment group and the respective baseline quality-of-life measure as predictors.
	Method	ANCOVA
	Comments	[Not Specified]

10. Secondary Outcome

Title	Summary of All Deaths
Description	All deaths, regardless of possible relatedness, with the exception of 1 event, were adjudicated by the Clinical Endpoint Committee (CEC) and are reported in this table. The 1 event which was not adjudicated was a result of the revocation of consent by the participant prior to their death. Deaths possibly related to study drug in the opinion of the investigator are also contained in the Serious Adverse Event (SAE) module.
Time Frame	Randomization through end of study (30-month visit)

Outcome Measure Data

Analysis Population Description

All randomized participants

Arm/Group Title	Prasugrel: <75 Years of Age	Prasugrel: 75 Years of Age or Older	Clopidogrel: <75 Years of Age	Clopidogrel: 75 Years of Age or Older
Arm/Group Description:	Prasugrel and Low-dose Commercially-available Aspirin in participants less than (<) 75 years of age. Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study. Prasugrel: 30 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and either 5 mg or 10 mg (based upon weight) orally, once daily as maintenance dose through end of study.	Prasugrel and Low-dose Commercially-available Aspirin in participants 75 years of age or older. Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study. Prasugrel: 30 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and either 5 mg orally, once daily as maintenance dose through end of study.	Clopidogrel and Low-Dose Commercially-available Aspirin in participants less than (<) 75 years of age. Commercially-available Aspirin : Low-dose aspirin, oral, as prescribed by physician through end of study Clopidogrel : 300 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and 75 mg, oral, once daily as maintenance dose through end of study	Clopidogrel and Low-Dose Commercially-available Aspirin in participants 75 years of age or older. Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study. Clopidogrel: 300 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and 75 mg, oral, once daily as maintenance dose through end of study.
Overall Number of Participants Analyzed	3620	1043	3623	1040
Measure Type: Number; Unit of Measure: participants
Congestive Heart Failure	10	21	13	23
Cardiogenic Shock	8	4	10	9
Cardiac Rupture	0	1	0	0
Myocardial Infarction	16	24	24	21
Dysrhythmia	5	2	6	3
Stent Thrombosis	0	0	0	0
Directly Related to Revascularization-CABG or PCI	1	1	1	1
Intracranial Hemorrhage	2	1	4	1
Non-Hemorrhagic Stroke	4	4	4	3
Sudden death due to cardiovascular event	75	39	70	43
Pulmonary Embolism	0	1	2	1
Stroke, unknown type	0	1	0	0
Other Cardiovascular Event	6	1	0	1
Cardiovascular event, unknown type	40	41	45	45
Accidental	1	0	1	1
Trauma	2	3	0	1
Hemorrhage, not intracranial	1	1	0	4
Infection	14	21	16	17
Malignancy	14	7	14	11
Suicide	1	0	0	0
Other Non-Cardiovascular event	8	4	8	6
Cause unknown (nonadjudicated event)	0	1	0	0

Adverse Events

Time Frame	[Not Specified]
Adverse Event Reporting Description	Events leading to death, MI, stroke, stent thrombosis, or rehospitalization for recurrent UA were not recorded as an SAEs unless the event was possibly due to study drug.
Arm/Group Title	Prasugrel		Clopidogrel
Arm/Group Description	Prasugrel and Low-dose Commercially-available Aspirin in participants. Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study Prasugrel: 30 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and either 5 mg or 10 mg (based upon weight and age), oral, once daily as maintenance dose through end of study.		Clopidogrel and Low-Dose Commercially-available Aspirin in participants. Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study. Clopidogrel: 300 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and 75 mg, oral, once daily as maintenance dose through end of study.
All-Cause Mortality
	Prasugrel		Clopidogrel
	Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--
Serious Adverse Events
	Prasugrel		Clopidogrel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1573/4623 (34.03%)		1594/4617 (34.52%)
Blood and lymphatic system disorders
Anaemia † 1	23/4623 (0.50%)	23	23/4617 (0.50%)	23
Anaemia haemolytic autoimmune † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Autoimmune thrombocytopenia † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Bicytopenia † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Coagulopathy † 1	0/4623 (0.00%)	0	2/4617 (0.04%)	2
Haemorrhagic anaemia † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Hypochromic anaemia † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Iron deficiency anaemia † 1	3/4623 (0.06%)	3	5/4617 (0.11%)	5
Microcytic anaemia † 1	1/4623 (0.02%)	1	1/4617 (0.02%)	1
Normochromic normocytic anaemia † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Pancytopenia † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Red blood cell abnormality † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Splenic infarction † 1	1/4623 (0.02%)	1	1/4617 (0.02%)	1
Thrombocytopenia † 1	1/4623 (0.02%)	1	1/4617 (0.02%)	1
Cardiac disorders
Acute coronary syndrome † 1	17/4623 (0.37%)	17	19/4617 (0.41%)	24
Acute left ventricular failure † 1	8/4623 (0.17%)	11	9/4617 (0.19%)	10
Acute myocardial infarction † 1	194/4623 (4.20%)	241	194/4617 (4.20%)	244
Angina pectoris † 1	115/4623 (2.49%)	125	129/4617 (2.79%)	139
Angina unstable † 1	290/4623 (6.27%)	351	310/4617 (6.71%)	374
Aortic valve disease † 1	1/4623 (0.02%)	1	1/4617 (0.02%)	1
Aortic valve incompetence † 1	2/4623 (0.04%)	2	2/4617 (0.04%)	2
Aortic valve stenosis † 1	2/4623 (0.04%)	2	1/4617 (0.02%)	1
Arrhythmia † 1	7/4623 (0.15%)	7	2/4617 (0.04%)	2
Arrhythmia supraventricular † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Arteriosclerosis coronary artery † 1	4/4623 (0.09%)	4	4/4617 (0.09%)	4
Arteriospasm coronary † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Atrial fibrillation † 1	82/4623 (1.77%)	88	69/4617 (1.49%)	71
Atrial flutter † 1	12/4623 (0.26%)	12	4/4617 (0.09%)	5
Atrial tachycardia † 1	2/4623 (0.04%)	2	3/4617 (0.06%)	3
Atrial thrombosis † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Atrioventricular block † 1	3/4623 (0.06%)	3	6/4617 (0.13%)	7
Atrioventricular block complete † 1	2/4623 (0.04%)	2	5/4617 (0.11%)	5
Atrioventricular block second degree † 1	0/4623 (0.00%)	0	2/4617 (0.04%)	2
Bradyarrhythmia † 1	1/4623 (0.02%)	1	1/4617 (0.02%)	1
Bradycardia † 1	7/4623 (0.15%)	8	14/4617 (0.30%)	14
Bundle branch block left † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Bundle branch block right † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Cardiac arrest † 1	29/4623 (0.63%)	30	28/4617 (0.61%)	28
Cardiac disorder † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Cardiac failure † 1	68/4623 (1.47%)	75	67/4617 (1.45%)	81
Cardiac failure acute † 1	12/4623 (0.26%)	12	19/4617 (0.41%)	19
Cardiac failure chronic † 1	36/4623 (0.78%)	36	41/4617 (0.89%)	41
Cardiac failure congestive † 1	83/4623 (1.80%)	96	104/4617 (2.25%)	111
Cardiac flutter † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Cardiac tamponade † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Cardiac valve disease † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Cardio-respiratory arrest † 1	8/4623 (0.17%)	8	14/4617 (0.30%)	14
Cardiogenic shock † 1	15/4623 (0.32%)	15	23/4617 (0.50%)	23
Cardiomegaly † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Cardiomyopathy † 1	3/4623 (0.06%)	3	1/4617 (0.02%)	1
Cardiopulmonary failure † 1	5/4623 (0.11%)	5	3/4617 (0.06%)	3
Cardiovascular insufficiency † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Congestive cardiomyopathy † 1	2/4623 (0.04%)	2	1/4617 (0.02%)	2
Cor pulmonale † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Coronary artery disease † 1	43/4623 (0.93%)	43	39/4617 (0.84%)	39
Coronary artery dissection † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Coronary artery occlusion † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Coronary artery perforation † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Coronary artery stenosis † 1	8/4623 (0.17%)	8	7/4617 (0.15%)	7
Coronary artery thrombosis † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Diastolic dysfunction † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Ischaemic cardiomyopathy † 1	4/4623 (0.09%)	4	3/4617 (0.06%)	3
Left ventricular dysfunction † 1	1/4623 (0.02%)	1	2/4617 (0.04%)	2
Left ventricular failure † 1	4/4623 (0.09%)	4	8/4617 (0.17%)	8
Low cardiac output syndrome † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Mitral valve disease † 1	1/4623 (0.02%)	1	1/4617 (0.02%)	1
Mitral valve incompetence † 1	2/4623 (0.04%)	2	1/4617 (0.02%)	1
Myocardial fibrosis † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Myocardial infarction † 1	142/4623 (3.07%)	166	143/4617 (3.10%)	166
Myocardial ischaemia † 1	31/4623 (0.67%)	31	41/4617 (0.89%)	41
Palpitations † 1	2/4623 (0.04%)	2	3/4617 (0.06%)	3
Pericardial effusion † 1	2/4623 (0.04%)	2	0/4617 (0.00%)	0
Pericarditis † 1	2/4623 (0.04%)	2	0/4617 (0.00%)	0
Postinfarction angina † 1	5/4623 (0.11%)	5	4/4617 (0.09%)	4
Prinzmetal angina † 1	2/4623 (0.04%)	2	0/4617 (0.00%)	0
Sick sinus syndrome † 1	1/4623 (0.02%)	1	3/4617 (0.06%)	3
Sinus arrest † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Sinus bradycardia † 1	2/4623 (0.04%)	2	1/4617 (0.02%)	1
Stress cardiomyopathy † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Supraventricular tachycardia † 1	4/4623 (0.09%)	4	8/4617 (0.17%)	8
Tachycardia † 1	1/4623 (0.02%)	1	3/4617 (0.06%)	3
Ventricle rupture † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Ventricular arrhythmia † 1	4/4623 (0.09%)	4	0/4617 (0.00%)	0
Ventricular extrasystoles † 1	2/4623 (0.04%)	2	5/4617 (0.11%)	5
Ventricular fibrillation † 1	3/4623 (0.06%)	3	15/4617 (0.32%)	17
Ventricular tachycardia † 1	15/4623 (0.32%)	17	20/4617 (0.43%)	23
Congenital, familial and genetic disorders
Branchial cyst † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Gastrointestinal angiodysplasia † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Glucose-6-phosphate dehydrogenase deficiency † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Hydrocele † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Phimosis † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Ear and labyrinth disorders
Deafness unilateral † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Vertigo † 1	5/4623 (0.11%)	5	4/4617 (0.09%)	4
Vertigo positional † 1	1/4623 (0.02%)	1	2/4617 (0.04%)	2
Endocrine disorders
Goitre † 1	1/4623 (0.02%)	1	1/4617 (0.02%)	1
Hyperthyroidism † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Primary hyperaldosteronism † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Primary hypothyroidism † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Eye disorders
Amaurosis † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Cataract † 1	8/4623 (0.17%)	9	4/4617 (0.09%)	5
Conjunctival haemorrhage † 1	1/4623 (0.02%)	1	1/4617 (0.02%)	1
Corneal oedema † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Diabetic retinopathy † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	2
Diplopia † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Eye haemorrhage † 1	1/4623 (0.02%)	1	1/4617 (0.02%)	1
Glaucoma † 1	0/4623 (0.00%)	0	2/4617 (0.04%)	2
Open angle glaucoma † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Ophthalmoplegia † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Retinal artery occlusion † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Retinal detachment † 1	0/4623 (0.00%)	0	2/4617 (0.04%)	3
Retinal haemorrhage † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Retinal vein thrombosis † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Vision blurred † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Vitreous haemorrhage † 1	1/4623 (0.02%)	1	2/4617 (0.04%)	2
Gastrointestinal disorders
Abdominal adhesions † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Abdominal hernia † 1	2/4623 (0.04%)	2	2/4617 (0.04%)	2
Abdominal hernia obstructive † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Abdominal pain † 1	6/4623 (0.13%)	6	6/4617 (0.13%)	6
Abdominal pain lower † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Abdominal pain upper † 1	3/4623 (0.06%)	3	4/4617 (0.09%)	4
Abdominal wall haematoma † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Acute abdomen † 1	2/4623 (0.04%)	2	0/4617 (0.00%)	0
Anal fissure † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Anal fistula † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Ascites † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Colitis † 1	1/4623 (0.02%)	1	1/4617 (0.02%)	1
Colitis ischaemic † 1	1/4623 (0.02%)	1	2/4617 (0.04%)	2
Colonic polyp † 1	3/4623 (0.06%)	3	2/4617 (0.04%)	2
Constipation † 1	2/4623 (0.04%)	2	3/4617 (0.06%)	3
Dental caries † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Diarrhoea † 1	1/4623 (0.02%)	1	4/4617 (0.09%)	4
Diarrhoea haemorrhagic † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Diverticulum † 1	1/4623 (0.02%)	1	2/4617 (0.04%)	2
Diverticulum intestinal † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Diverticulum intestinal haemorrhagic † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Duodenal polyp † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Duodenal ulcer † 1	6/4623 (0.13%)	6	4/4617 (0.09%)	4
Duodenal ulcer haemorrhage † 1	4/4623 (0.09%)	4	2/4617 (0.04%)	2
Duodenitis † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Dyspepsia † 1	5/4623 (0.11%)	5	2/4617 (0.04%)	2
Dysphagia † 1	3/4623 (0.06%)	3	4/4617 (0.09%)	4
Enteritis † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Epigastric discomfort † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Erosive duodenitis † 1	2/4623 (0.04%)	2	0/4617 (0.00%)	0
Faecaloma † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Femoral hernia † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Gastric disorder † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Gastric haemorrhage † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Gastric ulcer † 1	3/4623 (0.06%)	3	1/4617 (0.02%)	1
Gastric ulcer haemorrhage † 1	3/4623 (0.06%)	3	2/4617 (0.04%)	2
Gastric ulcer, obstructive † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Gastritis † 1	11/4623 (0.24%)	11	4/4617 (0.09%)	4
Gastritis erosive † 1	2/4623 (0.04%)	2	3/4617 (0.06%)	3
Gastritis haemorrhagic † 1	0/4623 (0.00%)	0	2/4617 (0.04%)	2
Gastrointestinal disorder † 1	2/4623 (0.04%)	2	1/4617 (0.02%)	1
Gastrointestinal haemorrhage † 1	39/4623 (0.84%)	39	22/4617 (0.48%)	22
Gastrointestinal inflammation † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Gastrointestinal pain † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Gastrointestinal ulcer haemorrhage † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Gastrooesophageal reflux disease † 1	6/4623 (0.13%)	6	3/4617 (0.06%)	3
Gingival bleeding † 1	1/4623 (0.02%)	1	1/4617 (0.02%)	1
Haematemesis † 1	6/4623 (0.13%)	6	0/4617 (0.00%)	0
Haematochezia † 1	2/4623 (0.04%)	2	2/4617 (0.04%)	2
Haemorrhagic erosive gastritis † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Haemorrhoidal haemorrhage † 1	1/4623 (0.02%)	1	3/4617 (0.06%)	3
Haemorrhoids † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Hiatus hernia † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Ileus † 1	1/4623 (0.02%)	1	1/4617 (0.02%)	1
Ileus paralytic † 1	1/4623 (0.02%)	1	1/4617 (0.02%)	1
Impaired gastric emptying † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Inguinal hernia † 1	2/4623 (0.04%)	3	6/4617 (0.13%)	6
Inguinal hernia strangulated † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Inguinal hernia, obstructive † 1	1/4623 (0.02%)	1	2/4617 (0.04%)	2
Intestinal angina † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Intestinal fistula † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Intestinal haemorrhage † 1	1/4623 (0.02%)	1	2/4617 (0.04%)	2
Intestinal ischaemia † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Intestinal mass † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Intestinal obstruction † 1	1/4623 (0.02%)	1	3/4617 (0.06%)	3
Irritable bowel syndrome † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Localised intraabdominal fluid collection † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Lower gastrointestinal haemorrhage † 1	8/4623 (0.17%)	8	3/4617 (0.06%)	3
Mallory-weiss syndrome † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Melaena † 1	4/4623 (0.09%)	4	1/4617 (0.02%)	1
Mesenteric artery embolism † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Nausea † 1	1/4623 (0.02%)	1	2/4617 (0.04%)	2
Oesophageal ulcer † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Oesophageal ulcer haemorrhage † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Oesophagitis † 1	1/4623 (0.02%)	1	1/4617 (0.02%)	1
Palatal oedema † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Pancreatitis † 1	1/4623 (0.02%)	1	5/4617 (0.11%)	6
Pancreatitis acute † 1	2/4623 (0.04%)	2	5/4617 (0.11%)	5
Pancreatitis chronic † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Pancreatitis haemorrhagic † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Pancreatitis relapsing † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Peptic ulcer † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Rectal haemorrhage † 1	11/4623 (0.24%)	12	4/4617 (0.09%)	4
Retroperitoneal haemorrhage † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Sigmoiditis † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Small intestinal obstruction † 1	3/4623 (0.06%)	5	3/4617 (0.06%)	4
Small intestinal perforation † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Subileus † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Umbilical hernia † 1	1/4623 (0.02%)	1	1/4617 (0.02%)	1
Upper gastrointestinal haemorrhage † 1	20/4623 (0.43%)	21	15/4617 (0.32%)	15
Varices oesophageal † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Vomiting † 1	2/4623 (0.04%)	2	1/4617 (0.02%)	1
General disorders
Adverse drug reaction † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Asthenia † 1	8/4623 (0.17%)	8	3/4617 (0.06%)	3
Cardiac death † 1	2/4623 (0.04%)	2	1/4617 (0.02%)	1
Chest discomfort † 1	3/4623 (0.06%)	3	4/4617 (0.09%)	4
Chest pain † 1	13/4623 (0.28%)	14	5/4617 (0.11%)	6
Chills † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Death † 1	34/4623 (0.74%)	34	40/4617 (0.87%)	40
Device malfunction † 1	1/4623 (0.02%)	1	1/4617 (0.02%)	1
Euthanasia † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Generalised oedema † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Hernia † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Impaired healing † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Malaise † 1	2/4623 (0.04%)	2	0/4617 (0.00%)	0
Medical device complication † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Multi-organ failure † 1	3/4623 (0.06%)	3	5/4617 (0.11%)	5
Necrosis † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Non-cardiac chest pain † 1	66/4623 (1.43%)	71	65/4617 (1.41%)	78
Oedema peripheral † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Pyrexia † 1	3/4623 (0.06%)	3	3/4617 (0.06%)	3
Sudden cardiac death † 1	12/4623 (0.26%)	12	16/4617 (0.35%)	16
Sudden death † 1	45/4623 (0.97%)	45	46/4617 (1.00%)	46
Thrombosis in device † 1	12/4623 (0.26%)	13	23/4617 (0.50%)	24
Ulcer haemorrhage † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Hepatobiliary disorders
Bile duct obstruction † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Bile duct stone † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Biliary tract disorder † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Cholecystitis † 1	6/4623 (0.13%)	6	4/4617 (0.09%)	4
Cholecystitis acute † 1	9/4623 (0.19%)	10	8/4617 (0.17%)	9
Cholecystitis chronic † 1	1/4623 (0.02%)	1	3/4617 (0.06%)	3
Cholelithiasis † 1	4/4623 (0.09%)	4	10/4617 (0.22%)	10
Cholestasis † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Hepatic cirrhosis † 1	4/4623 (0.09%)	4	0/4617 (0.00%)	0
Hepatic failure † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Hepatitis † 1	0/4623 (0.00%)	0	2/4617 (0.04%)	2
Hyperplastic cholecystopathy † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Portal vein thrombosis † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Immune system disorders
Atopy † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Drug hypersensitivity † 1	1/4623 (0.02%)	1	1/4617 (0.02%)	1
Hypersensitivity † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Immunosuppression † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Kidney transplant rejection † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	2
Infections and infestations
Abdominal abscess † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Abdominal sepsis † 1	1/4623 (0.02%)	1	1/4617 (0.02%)	1
Abdominal wall abscess † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Abscess limb † 1	2/4623 (0.04%)	2	1/4617 (0.02%)	1
Abscess neck † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	2
Acute sinusitis † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Anal abscess † 1	1/4623 (0.02%)	1	2/4617 (0.04%)	2
Appendiceal abscess † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Appendicitis † 1	1/4623 (0.02%)	1	3/4617 (0.06%)	3
Appendicitis perforated † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Bacteraemia † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Bronchitis † 1	11/4623 (0.24%)	12	15/4617 (0.32%)	15
Bronchitis bacterial † 1	0/4623 (0.00%)	0	2/4617 (0.04%)	2
Bronchopneumonia † 1	8/4623 (0.17%)	8	8/4617 (0.17%)	10
Bronchopulmonary aspergillosis † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Burkholderia cepacia complex infection † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Burkholderia pseudomallei infection † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Cellulitis † 1	9/4623 (0.19%)	9	11/4617 (0.24%)	12
Cholecystitis infective † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Cystitis † 1	1/4623 (0.02%)	1	1/4617 (0.02%)	1
Cytomegalovirus colitis † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Device related infection † 1	2/4623 (0.04%)	2	0/4617 (0.00%)	0
Diabetic gangrene † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Diarrhoea infectious † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Disseminated tuberculosis † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Diverticulitis † 1	3/4623 (0.06%)	3	1/4617 (0.02%)	1
Ear infection † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Eczema infected † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Enterocolitis bacterial † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Erysipelas † 1	2/4623 (0.04%)	2	5/4617 (0.11%)	5
Escherichia urinary tract infection † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Fungal infection † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Furuncle † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Gangrene † 1	4/4623 (0.09%)	4	1/4617 (0.02%)	1
Gastroenteritis † 1	7/4623 (0.15%)	7	7/4617 (0.15%)	7
Gastroenteritis norovirus † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Gastroenteritis viral † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Gastrointestinal viral infection † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Groin abscess † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Haematoma infection † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Helicobacter gastritis † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Hepatitis b † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Hepatitis c † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Herpes zoster † 1	2/4623 (0.04%)	2	0/4617 (0.00%)	0
Herpes zoster ophthalmic † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Infection † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Infectious peritonitis † 1	1/4623 (0.02%)	1	1/4617 (0.02%)	1
Infective exacerbation of chronic obstructive airways disease † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Labyrinthitis † 1	2/4623 (0.04%)	2	1/4617 (0.02%)	1
Lobar pneumonia † 1	2/4623 (0.04%)	2	1/4617 (0.02%)	1
Localised infection † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Lower respiratory tract infection † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Lower respiratory tract infection viral † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Lung abscess † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Lung infection † 1	0/4623 (0.00%)	0	2/4617 (0.04%)	2
Lymphangitis † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Malaria † 1	2/4623 (0.04%)	2	0/4617 (0.00%)	0
Mediastinitis † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Meningitis tuberculous † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Muscle abscess † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Onychomycosis † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Orchitis † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Osteomyelitis † 1	5/4623 (0.11%)	5	4/4617 (0.09%)	4
Osteomyelitis chronic † 1	1/4623 (0.02%)	1	1/4617 (0.02%)	1
Parametritis † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Paronychia † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Peridiverticular abscess † 1	2/4623 (0.04%)	2	0/4617 (0.00%)	0
Perirectal abscess † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Pneumonia † 1	74/4623 (1.60%)	86	76/4617 (1.65%)	79
Pneumonia bacterial † 1	2/4623 (0.04%)	2	0/4617 (0.00%)	0
Pneumonia haemophilus † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Pneumonia mycoplasmal † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Pneumonia staphylococcal † 1	1/4623 (0.02%)	1	1/4617 (0.02%)	1
Pneumonia viral † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Post procedural infection † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Postoperative wound infection † 1	2/4623 (0.04%)	2	1/4617 (0.02%)	1
Pulmonary tuberculosis † 1	1/4623 (0.02%)	1	1/4617 (0.02%)	1
Pyelonephritis † 1	1/4623 (0.02%)	1	2/4617 (0.04%)	2
Pyelonephritis acute † 1	2/4623 (0.04%)	2	2/4617 (0.04%)	2
Pyelonephritis chronic † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Pyonephrosis † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Rectal abscess † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Renal abscess † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Respiratory tract infection † 1	3/4623 (0.06%)	3	7/4617 (0.15%)	7
Salmonellosis † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Scrotal abscess † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Sepsis † 1	11/4623 (0.24%)	11	12/4617 (0.26%)	12
Septic shock † 1	6/4623 (0.13%)	6	8/4617 (0.17%)	8
Sinusitis † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Skin infection † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Staphylococcal bacteraemia † 1	1/4623 (0.02%)	1	1/4617 (0.02%)	1
Staphylococcal infection † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Staphylococcal sepsis † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Subcutaneous abscess † 1	2/4623 (0.04%)	2	0/4617 (0.00%)	0
Tracheobronchitis † 1	2/4623 (0.04%)	2	2/4617 (0.04%)	2
Tuberculosis † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Upper respiratory tract infection † 1	2/4623 (0.04%)	2	2/4617 (0.04%)	2
Urinary tract infection † 1	33/4623 (0.71%)	34	19/4617 (0.41%)	20
Urosepsis † 1	4/4623 (0.09%)	4	3/4617 (0.06%)	3
Viral diarrhoea † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Viral infection † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Viral upper respiratory tract infection † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Wound infection † 1	1/4623 (0.02%)	1	2/4617 (0.04%)	2
Injury, poisoning and procedural complications
Accidental overdose † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Alcohol poisoning † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Ankle fracture † 1	2/4623 (0.04%)	2	4/4617 (0.09%)	4
Arteriovenous fistula site haemorrhage † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Brain contusion † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Chemical burns of eye † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Concussion † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Confusion postoperative † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Contusion † 1	1/4623 (0.02%)	1	3/4617 (0.06%)	3
Coronary artery restenosis † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Face injury † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Facial bones fracture † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Fall † 1	5/4623 (0.11%)	5	1/4617 (0.02%)	1
Femoral neck fracture † 1	1/4623 (0.02%)	1	3/4617 (0.06%)	3
Femur fracture † 1	7/4623 (0.15%)	7	7/4617 (0.15%)	7
Fibula fracture † 1	0/4623 (0.00%)	0	2/4617 (0.04%)	2
Foot fracture † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Gun shot wound † 1	1/4623 (0.02%)	1	2/4617 (0.04%)	2
Haematuria traumatic † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Hand fracture † 1	2/4623 (0.04%)	2	1/4617 (0.02%)	1
Head injury † 1	2/4623 (0.04%)	2	1/4617 (0.02%)	1
Hip fracture † 1	6/4623 (0.13%)	6	6/4617 (0.13%)	6
Humerus fracture † 1	1/4623 (0.02%)	1	1/4617 (0.02%)	1
In-stent coronary artery restenosis † 1	3/4623 (0.06%)	3	7/4617 (0.15%)	7
Incisional hernia, obstructive † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Joint dislocation † 1	1/4623 (0.02%)	1	1/4617 (0.02%)	1
Limb injury † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Lower limb fracture † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Lumbar vertebral fracture † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Multiple drug overdose † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Muscle rupture † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Operative haemorrhage † 1	0/4623 (0.00%)	0	2/4617 (0.04%)	2
Overdose † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Pelvic fracture † 1	1/4623 (0.02%)	1	1/4617 (0.02%)	1
Periorbital haematoma † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Periorbital haemorrhage † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Poisoning † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Post procedural haematoma † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Post procedural haemorrhage † 1	5/4623 (0.11%)	5	4/4617 (0.09%)	4
Post procedural myocardial infarction † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Postoperative fever † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Postoperative thrombosis † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Postoperative wound complication † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Pubis fracture † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Rib fracture † 1	3/4623 (0.06%)	3	2/4617 (0.04%)	2
Road traffic accident † 1	4/4623 (0.09%)	4	1/4617 (0.02%)	1
Scapula fracture † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Skeletal injury † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Skull fractured base † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Soft tissue injury † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Spinal column injury † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Spinal compression fracture † 1	0/4623 (0.00%)	0	2/4617 (0.04%)	2
Spinal fracture † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Splenic rupture † 1	0/4623 (0.00%)	0	2/4617 (0.04%)	2
Stab wound † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Sternal fracture † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Subcutaneous haematoma † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Subdural haematoma † 1	7/4623 (0.15%)	8	7/4617 (0.15%)	7
Subdural haemorrhage † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Tendon rupture † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Thermal burn † 1	1/4623 (0.02%)	1	3/4617 (0.06%)	3
Tibia fracture † 1	1/4623 (0.02%)	1	2/4617 (0.04%)	2
Tooth fracture † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Toxicity to various agents † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Traumatic haematoma † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Traumatic intracranial haemorrhage † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Vascular graft occlusion † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Vascular pseudoaneurysm † 1	3/4623 (0.06%)	3	2/4617 (0.04%)	2
Weaning failure † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Wound † 1	2/4623 (0.04%)	2	0/4617 (0.00%)	0
Wound dehiscence † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Wound haemorrhage † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Wound secretion † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Investigations
Acinetobacter test positive † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Alanine aminotransferase increased † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Angiogram † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Aspartate aminotransferase increased † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Blood glucose fluctuation † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Blood glucose increased † 1	2/4623 (0.04%)	2	0/4617 (0.00%)	0
Blood pressure increased † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Catheterisation cardiac † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Coagulation time prolonged † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Ejection fraction decreased † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Electrocardiogram qt prolonged † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Electrocardiogram st segment elevation † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Haematocrit decreased † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Haemoglobin decreased † 1	2/4623 (0.04%)	2	1/4617 (0.02%)	1
Hepatic enzyme increased † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Occult blood † 1	1/4623 (0.02%)	1	1/4617 (0.02%)	1
Prostatic specific antigen increased † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Metabolism and nutrition disorders
Acidosis † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Cachexia † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Dehydration † 1	4/4623 (0.09%)	4	5/4617 (0.11%)	5
Diabetes mellitus † 1	13/4623 (0.28%)	13	9/4617 (0.19%)	9
Diabetes mellitus inadequate control † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Diabetic foot † 1	5/4623 (0.11%)	5	3/4617 (0.06%)	3
Diabetic ketoacidosis † 1	3/4623 (0.06%)	4	5/4617 (0.11%)	5
Electrolyte imbalance † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Failure to thrive † 1	1/4623 (0.02%)	1	1/4617 (0.02%)	1
Fluid overload † 1	2/4623 (0.04%)	2	0/4617 (0.00%)	0
Gout † 1	1/4623 (0.02%)	1	1/4617 (0.02%)	1
Hyperglycaemia † 1	6/4623 (0.13%)	7	5/4617 (0.11%)	6
Hyperkalaemia † 1	3/4623 (0.06%)	3	8/4617 (0.17%)	8
Hypoglycaemia † 1	10/4623 (0.22%)	11	13/4617 (0.28%)	14
Hypokalaemia † 1	1/4623 (0.02%)	1	3/4617 (0.06%)	3
Hyponatraemia † 1	6/4623 (0.13%)	6	4/4617 (0.09%)	4
Hypovolaemia † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Metabolic acidosis † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Obesity † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Shock hypoglycaemic † 1	1/4623 (0.02%)	1	1/4617 (0.02%)	1
Type 2 diabetes mellitus † 1	0/4623 (0.00%)	0	2/4617 (0.04%)	2
Musculoskeletal and connective tissue disorders
Arthralgia † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Arthritis † 1	0/4623 (0.00%)	0	2/4617 (0.04%)	2
Back pain † 1	5/4623 (0.11%)	5	5/4617 (0.11%)	5
Bursitis † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Cervical spinal stenosis † 1	1/4623 (0.02%)	1	1/4617 (0.02%)	1
Costochondritis † 1	2/4623 (0.04%)	2	4/4617 (0.09%)	4
Dupuytren's contracture † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Gouty arthritis † 1	1/4623 (0.02%)	1	2/4617 (0.04%)	2
Haemarthrosis † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Intervertebral disc degeneration † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Intervertebral disc disorder † 1	2/4623 (0.04%)	2	0/4617 (0.00%)	0
Intervertebral disc protrusion † 1	5/4623 (0.11%)	5	2/4617 (0.04%)	3
Joint effusion † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Musculoskeletal chest pain † 1	5/4623 (0.11%)	5	5/4617 (0.11%)	5
Musculoskeletal pain † 1	5/4623 (0.11%)	5	1/4617 (0.02%)	1
Myalgia † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Myopathy † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Osteoarthritis † 1	6/4623 (0.13%)	6	11/4617 (0.24%)	11
Osteochondritis † 1	1/4623 (0.02%)	1	1/4617 (0.02%)	1
Osteoporosis † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Pain in extremity † 1	1/4623 (0.02%)	1	1/4617 (0.02%)	1
Periarthritis † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Psoriatic arthropathy † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Rhabdomyolysis † 1	1/4623 (0.02%)	1	2/4617 (0.04%)	2
Rheumatoid arthritis † 1	2/4623 (0.04%)	2	1/4617 (0.02%)	1
Spinal column stenosis † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Spinal osteoarthritis † 1	1/4623 (0.02%)	1	4/4617 (0.09%)	4
Spondylitis † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Synovial cyst † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Synovitis † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Tenosynovitis † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Vertebral foraminal stenosis † 1	0/4623 (0.00%)	0	1/4617 (0.02%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Benign laryngeal neoplasm † 1	1/4623 (0.02%)	1	0/4617 (0.00%)	0
Benign ovarian tumour † 1	1/4623 (0.02%)