The Dual Antiplatelet Therapy Study (DAPT Study)

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ClinicalTrials.gov Identifier: NCT00977938

Recruitment Status : Completed

First Posted : September 16, 2009

Results First Posted : October 22, 2015

Last Update Posted : June 9, 2017

View this study on Beta.ClinicalTrials.gov

Sponsor:

Collaborators:

Abbott

Boston Scientific Corporation

Bristol-Myers Squibb

Sanofi-Synthelabo

Cordis Corporation

Eli Lilly and Company

Daiichi Sankyo, Inc.

Medtronic

Information provided by (Responsible Party):

Baim Institute for Clinical Research

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Treatment
Condition	Coronary Artery Disease
Interventions	Drug: Placebo & Aspirin Drug: Clopidogrel & Aspirin, Prasugrel & Aspirin
Enrollment	25682

Participant Flow

Recruitment Details	Between 08/13/2009 and 07/01/2011, a total of 25682 patients were enrolled into the DAPT Study either by HCRI (NCT00977938; 14491 pts) or from 1 of 4 PMS studies: Abbott Xience V US (NCT01106534; 2998 pts), Boston Scientific Liberté PAS (NCT00997503; 3904 pts), Cordis CYPRESS (NCT00954707; 2029 pts) and Medtronic EDUCATE (NCT01069003; 2260 pts).
Pre-assignment Details


Arm/Group Title	DES 30-month DAPT	DES 12-month DAPT	BMS 30-month DAPT	BMS 12-month DAPT
Arm/Group Description	Of the 22,866 DES enrolled pts, a t...	Of the 22,866 DES enrolled pts, a t...	Of the 2,816 BMS enrolled pts, a to...	Of the 2,816 BMS enrolled pts, a to...
Arm/Group Description	Of the 22,866 DES enrolled pts, a total of 9,961 pts underwent randomization at 12 months (4,941 to 12m DAPT and 5,020 to 30m DAPT).	Of the 22,866 DES enrolled pts, a total of 9,961 pts underwent randomization at 12 months (4,941 to 12m DAPT and 5,020 to 30m DAPT).	Of the 2,816 BMS enrolled pts, a total of 1,687 pts underwent randomization at 12 months (845 to 12-month DAPT and 842 to 30-month DAPT).	Of the 2,816 BMS enrolled pts, a total of 1,687 pts underwent randomization at 12 months (845 to 12-month DAPT and 842 to 30-month DAPT).
Period Title: Treatment (12-30 mo. Post Procedure)
Started	5020	4941	842	845
Completed	4783	4716	796	784
Not Completed	237	225	46	61
Reason Not Completed
Withdrawal by Subject	132	116	13	20
Lost to Follow-up	88	91	30	37
Other	17	18	3	4
Period Title: Observation (30-33 mo. Post Procedure)
Started	4783	4716	796	784
Completed	4732	4658	784	781
Not Completed	51	58	12	3
Reason Not Completed
Withdrawal by Subject	9	12	2	0
Lost to Follow-up	34	42	10	3
Other	8	4	0	0

Baseline Characteristics

Arm/Group Title		DES 30-month DAPT	DES 12-month DAPT	BMS 30-month DAPT	BMS 12-month DAPT	Total
Arm/Group Description		Patients who were treated with DES ...	Patients who were treated with DES ...	Patients who were treated with BMS ...	Patients who were treated with BMS ...	Total of all reporting groups
Arm/Group Description		Patients who were treated with DES at the index procedure and were randomized at 12 months post procedure to receive a total of 30 months of DAPT	Patients who were treated with DES at the index procedure and were randomized at 12 months post procedure to receive a total of 12 months of DAPT	Patients who were treated with BMS at the index procedure and were randomized at 12 months post procedure to receive a total of 30 months of DAPT	Patients who were treated with BMS at the index procedure and were randomized at 12 months post procedure to receive a total of 12 months of DAPT	Total of all reporting groups
Overall Number of Baseline Participants		5020	4941	842	845	11648
Baseline Analysis Population Description		[Not Specified]
Baseline Analysis Population Description		[Not Specified]
Age, Continuous Mean (Standard Deviation) Unit of measure: Years
	Number Analyzed	5020 participants	4941 participants	842 participants	845 participants	11648 participants
		61.84 (10.18)	61.60 (10.12)	58.86 (10.54)	59.18 (11.07)	61.33 (10.29)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	5020 participants	4941 participants	842 participants	845 participants	11648 participants
	Female	1242 24.7%	1284 26.0%	215 25.5%	184 21.8%	2925 25.1%
	Male	3778 75.3%	3657 74.0%	627 74.5%	661 78.2%	8723 74.9%
Race/Ethnicity, Customized ^[1] Measure Type: Number Unit of measure: Participants	Number Analyzed	5020 participants	4941 participants	842 participants	845 participants	11648 participants
American Indian or Alaska Native		17	41	0	2	60
Asian		48	35	3	2	88
Black or African American		252	253	38	33	576
Native Hawaiian or Other Pacific Islander		13	9	1	1	24
White		4480	4428	768	774	10450
Other		108	106	20	23	257
		[1] Measure Description: Race was self-reported
Region of Enrollment Measure Type: Number Unit of measure: Participants	Number Analyzed	5020 participants	4941 participants	842 participants	845 participants	11648 participants
North America		4502	4416	509	519	9946
Europe		402	405	304	300	1411
Australia		47	55	14	12	128
New Zealand		69	65	15	14	163
weight Mean (Standard Deviation) Unit of measure: Kg
	Number Analyzed	5020 participants	4941 participants	842 participants	845 participants	11648 participants
		91.49 (19.74)	91.52 (19.43)	87.99 (18.40)	88.54 (18.77)	91.04 (19.48)
Body Mass Index (BMI) Mean (Standard Deviation) Unit of measure: Kg/m2
	Number Analyzed	5020 participants	4941 participants	842 participants	845 participants	11648 participants
		30.54 (5.79)	30.55 (5.77)	29.49 (5.18)	29.61 (5.55)	30.40 (5.73)
Diabetes Mellitus Measure Type: Number Unit of measure: Participants
	Number Analyzed	5020 participants	4941 participants	842 participants	845 participants	11648 participants
		1556	1481	181	173	3391
Hypertension Measure Type: Number Unit of measure: Participants
	Number Analyzed	5020 participants	4941 participants	842 participants	845 participants	11648 participants
		3796	3649	534	543	8522
Current cigarette smoker or within past year ^[1] Measure Type: Number Unit of measure: Participants
	Number Analyzed	5020 participants	4941 participants	842 participants	845 participants	11648 participants
		1222	1210	360	350	3142
		[1] Measure Description: "Current cigarette smoker or within past year" was defined as follows: HCRI DAPT: current cigarette smoker or within past year Abbott Xience V: current tobacco user or former tobacco user within the past month Boston Scientific Liberte PAS: smoking status of "current" from medical history Cordis CYPRESS: smoking within 30 days Medtronic EDUCATE: smoking/tobacco usage = "current" or "within last year"
Stroke/Transient Ischemic Attack (TIA) Measure Type: Number Unit of measure: Participants
	Number Analyzed	5020 participants	4941 participants	842 participants	845 participants	11648 participants
		155	169	43	34	401
Congestive heart failure Measure Type: Number Unit of measure: Participants
	Number Analyzed	5020 participants	4941 participants	842 participants	845 participants	11648 participants
		238	223	35	28	524
Peripheral arterial disease Measure Type: Number Unit of measure: Participants
	Number Analyzed	5020 participants	4941 participants	842 participants	845 participants	11648 participants
		284	284	35	46	649
Prior percutaneous coronary intervention (PCI) Measure Type: Number Unit of measure: Participants
	Number Analyzed	5020 participants	4941 participants	842 participants	845 participants	11648 participants
		1518	1529	150	171	3368
Prior coronary artery bypass graf (CABG) Measure Type: Number Unit of measure: Participants
	Number Analyzed	5020 participants	4941 participants	842 participants	845 participants	11648 participants
		568	581	50	50	1249
Prior myocardial infarction (MI) Measure Type: Number Unit of measure: Participants
	Number Analyzed	5020 participants	4941 participants	842 participants	845 participants	11648 participants
		1092	1026	160	178	2456
Indication for PCI ^[1] Measure Type: Number Unit of measure: Participants	Number Analyzed	5020 participants	4941 participants	842 participants	845 participants	11648 participants
ST elevation MI (STEMI)		534	511	311	324	1680
Non-ST elevation MI (NSTEMI)		776	767	184	169	1896
Unstable angina		838	825	77	81	1821
Stable angina		1882	1870	199	198	4149
Other		990	968	71	73	2102
		[1] Measure Description: "Unstable angina" includes unstable angina without reported elevation of cardiac enzymes
Any risk factor for stent thrombosis ^[1] Measure Type: Number Unit of measure: Participants
	Number Analyzed	5020 participants	4941 participants	842 participants	845 participants	11648 participants
		2410	2389	568	569	5936
		[1] Measure Description: Any clinical or lesion-related risk factors for stent thrombosis. Clinical risk factors for stent thrombosis included: Acute coronary syndrome (ACS) at presentation ST elevation MI (STEMI) at presentation Renal insufficiency or failure Ejection fraction <30%. Lesion-related risk factors for stent thrombosis included: More than two vessels stented >2 lesions per vessel Lesion length ≥30 mm Bifurcation lesion with side branch ≥2.5 mm In-stent restenosis of a DES Vein bypass graft Unprotected left main Thrombus containing lesion Prior brachytherapy
Number of treated lesions (per-patient) Mean (Standard Deviation) Unit of measure: Lesions
	Number Analyzed	5020 participants	4941 participants	842 participants	845 participants	11648 participants
		1.30 (0.55)	1.29 (0.54)	1.16 (0.40)	1.17 (0.42)	1.28 (0.53)
Number of treated vessels (per-patient) Mean (Standard Deviation) Unit of measure: Vessels
	Number Analyzed	5020 participants	4941 participants	842 participants	845 participants	11648 participants
		1.11 (0.33)	1.12 (0.34)	1.03 (0.18)	1.05 (0.23)	1.11 (0.32)
Number of stents (per-patient) Mean (Standard Deviation) Unit of measure: Stents
	Number Analyzed	5020 participants	4941 participants	842 participants	845 participants	11648 participants
		1.47 (0.75)	1.45 (0.75)	1.32 (0.60)	1.32 (0.60)	1.44 (0.73)
Minimum stent diameter (per-patient) Measure Type: Number Unit of measure: Participants	Number Analyzed	5020 participants	4941 participants	842 participants	845 participants	11648 participants
<3 mm		2341	2293	201	206	5041
≥3 mm		2679	2648	641	639	6607
Total stent length (per-patient) Mean (Standard Deviation) Unit of measure: Mm
	Number Analyzed	5020 participants	4941 participants	842 participants	845 participants	11648 participants
		27.70 (16.77)	27.43 (17.02)	23.96 (13.01)	23.85 (13.12)	27.04 (16.44)
Treated Vessel ^[1] Measure Type: Number Unit of measure: Lesions	Number Analyzed	5020 participants	4941 participants	842 participants	845 participants	11648 participants
Left main		55	55	0	1	111
Left anterior descending (LAD)		2715	2586	308	306	5915
Right coronary artery (RCA)		2153	2057	437	452	5099
Circumflex		1473	1506	206	207	3392
Venous graft		154	173	24	25	376
Arterial graft		36	30	0	0	66
		[1] Measure Description: The 5,020 DES 30-month DAPT patients had a total of 6,594 lesions; The 4,941 DES 12-month DAPT patients had a total of 6,413 lesions; The 842 BMS 30-month DAPT patients had a total of 975 lesions; The 845 BMS 12-month DAPT patients had a total of 991 lesions
Modified ACC-AHA lesion class B2 or C ^[1] Measure Type: Number Unit of measure: Lesions
	Number Analyzed	5020 participants	4941 participants	842 participants	845 participants	11648 participants
		2754	2643	440	450	6287
		[1] Measure Description: The 5,020 DES 30-month DAPT patients had a total of 6,594 lesions; The 4,941 DES 12-month DAPT patients had a total of 6,413 lesions; The 842 BMS 30-month DAPT patients had a total of 975 lesions; The 845 BMS 12-month DAPT patients had a total of 991 lesions; The definitions of class B2 and class C lesions according to the modified ACC/AHA criteria

Outcome Measures

1.Primary Outcome


Title	MACCE (Death, Myocardial Infarction or Stroke) - Randomized DES ITT
Description	The coprimary efficacy endpoints were the cumulative incidence of MACC...
Description	The coprimary efficacy endpoints were the cumulative incidence of MACCE and the cumulative incidence of ARC definite or probable stent thrombosis within randomized DES ITT patients between 12 and 30 months post procedure.
Time Frame	18 months (12-30 months post-index procedure)

Outcome Measure Data

Analysis Population Description

All randomized DES ITT patients; Patients were analyzed according to the treatment to which they were randomized (regardless of post-randomization compliance with the randomized treatment); Patients not experiencing the endpoint were censored at 30 months or at last known follow-up, whichever was earlier.


Arm/Group Title	DES 30-month DAPT	DES 12-month DAPT
Arm/Group Description:	Patients who were treated with DES ...	Patients who were treated with DES ...
Arm/Group Description:	Patients who were treated with DES at the index procedure and were randomized at 12 months post procedure to receive a total of 30 months of DAPT	Patients who were treated with DES at the index procedure and were randomized at 12 months post procedure to receive a total of 12 months of DAPT
Overall Number of Participants Analyzed	5020	4941
Measure Type: Number Unit of Measure: percentage of patients (KM estimate)
	4.34	5.92

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DES 30-month DAPT, DES 12-month DAPT
	Comments	The primary efficacy analysis was a superiority analysis. We controlled the two-sided family-wise error rate of 0.05 across the two coprimary end points using the Hochberg-Benjamini method. With this method, the null hypothesis of randomized treatment equivalence is rejected if significance is achieved for both end points at a two-sided alpha level of 0.05 or for one end point at a two-sided alpha level of 0.025.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	<0.001
	Comments	P-value was stratified according to geographic region (NA, EU, or AU and NZ), thienopyridine received at the time of randomization, and presence or absence of risk factors for ST; P-value was adjudsted using the Benjamini Hochberg approach.
	Method	Log Rank
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.71
	Confidence Interval	(2-Sided) 95% 0.59 to 0.85
	Estimation Comments	30-month DAPT vs. 12-month DAPT; HR was stratified according to geographic region (NA, EU, or AU and NZ), thienopyridine drug received at the time of randomization, and presence or absence of risk factors for stent thrombosis.

2.Primary Outcome


Title	Definite or Probable Stent Thrombosis (ST) - Randomized DES ITT
Description	The coprimary efficacy endpoints were the cumulative incidence of MACC...
Description	The coprimary efficacy endpoints were the cumulative incidence of MACCE and the cumulative incidence of definite or probable ST within randomized DES ITT patients between 12 and 30 months post procedure. ST was assessed according to the Academic Research Consortium (ARC) definitions.
Time Frame	18 months (12-30 months post-index procedure)

Outcome Measure Data

Analysis Population Description


Arm/Group Title	DES 30-month DAPT	DES 12-month DAPT
Arm/Group Description:	Patients who were treated with DES ...	Patients who were treated with DES ...
Arm/Group Description:	Patients who were treated with DES at the index procedure and were randomized at 12 months post procedure to receive a total of 30 months of DAPT	Patients who were treated with DES at the index procedure and were randomized at 12 months post procedure to receive a total of 12 months of DAPT
Overall Number of Participants Analyzed	5020	4941
Measure Type: Number Unit of Measure: percentage of patients (KM estimate)
	0.40	1.35

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DES 30-month DAPT, DES 12-month DAPT
	Comments	The primary efficacy analysis was a superiority analysis. We controlled the two-sided family-wise error rate of 0.05 across the two coprimary end points using the Hochberg-Benjamini method. With this method, the null hypothesis of randomized treatment equivalence is rejected if significance is achieved for both end points at a two-sided alpha level of 0.05 or for one end point at a two-sided alpha level of 0.025.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	<0.001
	Comments	P-value was stratified according to geographic region (NA, EU, or AU and NZ), thienopyridine received at the time of randomization, and presence or absence of risk factors for ST; P-value was adjudsted using the Benjamini Hochberg approach.
	Method	Log Rank
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.29
	Confidence Interval	(2-Sided) 95% 0.17 to 0.48
	Estimation Comments	30-month DAPT vs. 12-month DAPT; HR was stratified according to geographic region (NA, EU, or AU and NZ), thienopyridine drug received at the time of randomization, and presence or absence of risk factors for stent thrombosis.

3.Primary Outcome


Title	GUSTO Severe or Moderate Bleeding - Randomized DES ITT
Description	The primary safety endpoint was moderate or severe bleeding within ran...
Description	The primary safety endpoint was moderate or severe bleeding within randomized DES ITT patients between 12 and 30 months post procedure. Bleeding was assessed according to the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Arteries (GUSTO) criteria.
Time Frame	18 months (12-30 months post-index procedure)

Outcome Measure Data

Analysis Population Description

Only patients who could be evaluated were included in this analysis (i.e., patients whose last contact date was ≥510 days after randomization or who had any adjudicated bleeding event at or before 540 days).


Arm/Group Title	DES 30-month DAPT	DES 12-month DAPT
Arm/Group Description:	Patients who were treated with DES ...	Patients who were treated with DES ...
Arm/Group Description:	Patients who were treated with DES at the index procedure and were randomized at 12 months post procedure to receive a total of 30 months of DAPT	Patients who were treated with DES at the index procedure and were randomized at 12 months post procedure to receive a total of 12 months of DAPT
Overall Number of Participants Analyzed	4710	4649
Measure Type: Number Unit of Measure: percentage of patients
	2.53	1.57

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DES 30-month DAPT, DES 12-month DAPT
	Comments	[Not Specified]
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The primary safety analysis was a noninferiority analysis performed with the use of the Farrington-Manning risk-difference approach. Assuming an annualized rate for moderate or severe bleeding of 1.9% and an absolute noninferiority margin of 0.8%, at a one-sided alpha level of significance of 0.025, we calculated that a sample size of 9960 patients would give the study 80% power to detect noninferiority.

Statistical Test of Hypothesis	P-Value	0.704
	Comments	One-sided P-value for non-inferiority
	Method	Farrington-Manning
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	0.96
	Confidence Interval	(2-Sided) 95% 0.38 to 1.53
	Estimation Comments	30-month DAPT vs. 12-month DAPT

4.Secondary Outcome


Title	MACCE (Death, Myocardial Infarction or Stroke) - Propensity Matched DES vs. BMS
Description	Secondary powered endpoint
Description	Secondary powered endpoint
Time Frame	33 months (0-33 months post-index procedure)

Outcome Measure Data

Analysis Population Description

A subsample created by matching BMS- to DES-treated patients exactly on prevalence of STEMI and then matching on remaining baseline characteristics via propensity score, using a caliper width of 0.10. A BMS-treated patient was matched to a variable number of DES-treated patients without replacement, up to a maximum of 8.


Arm/Group Title	Propensity-matched DES	Propensity-matched BMS
Arm/Group Description:	Because patients were not randomize...	Because patients were not randomize...
Arm/Group Description:	Because patients were not randomized to DES or BMS, DES comparisons vs. BMS on stent thrombosis and MACCE were carried out on sample matched on baseline characteristics via propensity score matching. The analyses were restricted to patients enrolled into the 3 contributing studies that planned to follow all enrolled patients (whether or not a patient was randomized) for 33 months. Patients prematurely withdrawing before 29 months follow-up (earliest allowable follow-up time for the 30-month visit) or before experiencing the endpoint were excluded. A total of 13,257 DES-treated patients were eligible for propensity matching, of whom 8,308 patients were matched to BMS-treated patients (up to 8 DES patients could be matched to a BMS patient; i.e., the BMS:DES matching ratio ranged from 1:1 to 1:8).	Because patients were not randomized to DES or BMS, DES comparisons vs. BMS on stent thrombosis and MACCE were carried out on sample matched on baseline characteristics via propensity score matching. The analyses were restricted to patients enrolled into the 3 contributing studies that planned to follow all enrolled patients (whether or not a patient was randomized) for 33 months. Patients prematurely withdrawing before 29 months follow-up (earliest allowable follow-up time for the 30-month visit) or before experiencing the endpoint were excluded. A total of 2,056 BMS-treated patients were eligible for propensity matching, of whom 1,718 were matched to at least one DES-treated patient (a BMS patient could be matched to up to 8 DES patients; i.e., the BMS:DES matching ratio ranged from 1:1 to 1:8).
Overall Number of Participants Analyzed	8308	1718
Measure Type: Number Unit of Measure: percentage of patients
	11.37	13.24

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Propensity-matched DES, Propensity-matched BMS
	Comments	The null hypothesis was that DAPT patients treated with DES would have MACCE rate between 0 and 33 months post-index procedure that exceeds that of the control arm (patients treated with BMS) by at least a pre-specified absolute margin of δ.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority margin of 2.28% (0.0228)

Statistical Test of Hypothesis	P-Value	<0.001
	Comments	One-sided P-value for non-inferiority
	Method	Nam and Kwon
	Comments	P-value was computed for clustered matched pairs based on Nam and Kwon (2009).

Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-1.82
	Confidence Interval	(1-Sided) 97.5% 0.03
	Estimation Comments	Weighted RD and 1-sided 97.5% upper CL were computed for clustered matched pairs based on Nam and Kwon (2009).

5.Secondary Outcome


Title	Definite or Probable Stent Thrombosis (ST) - Propensity Matched DES vs. BMS
Description	Secondary powered endpoint
Description	Secondary powered endpoint
Time Frame	33 months (0-33 months post-index procedure)

Outcome Measure Data

Analysis Population Description


Arm/Group Title	Propensity-matched DES	Propensity-matched BMS
Arm/Group Description:	Because patients were not randomize...	Because patients were not randomize...
Arm/Group Description:	Because patients were not randomized to DES or BMS, DES comparisons vs. BMS on stent thrombosis and MACCE were carried out on sample matched on baseline characteristics via propensity score matching. The analyses were restricted to patients enrolled into the 3 contributing studies that planned to follow all enrolled patients (whether or not a patient was randomized) for 33 months. Patients prematurely withdrawing before 29 months follow-up (earliest allowable follow-up time for the 30-month visit) or before experiencing the endpoint were excluded. A total of 13,257 DES-treated patients were eligible for propensity matching, of whom 8,308 patients were matched to BMS-treated patients (up to 8 DES patients could be matched to a BMS patient; i.e., the BMS:DES matching ratio ranged from 1:1 to 1:8).	Because patients were not randomized to DES or BMS, DES comparisons vs. BMS on stent thrombosis and MACCE were carried out on sample matched on baseline characteristics via propensity score matching. The analyses were restricted to patients enrolled into the 3 contributing studies that planned to follow all enrolled patients (whether or not a patient was randomized) for 33 months. Patients prematurely withdrawing before 29 months follow-up (earliest allowable follow-up time for the 30-month visit) or before experiencing the endpoint were excluded. A total of 2,056 BMS-treated patients were eligible for propensity matching, of whom 1,718 were matched to at least one DES-treated patient (a BMS patient could be matched to up to 8 DES patients; i.e., the BMS:DES matching ratio ranged from 1:1 to 1:8).
Overall Number of Participants Analyzed	8308	1718
Measure Type: Number Unit of Measure: percentage of patients
	1.70	2.61

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Propensity-matched DES, Propensity-matched BMS
	Comments	The null hypothesis was that DAPT patients treated with DES would have stent thrombosis rate between 0 and 33 months post-index procedure that exceeds that of the control arm (patients treated with BMS) by at least a pre-specified absolute margin of δ.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority margin of 0.97% (0.0097)

Statistical Test of Hypothesis	P-Value	<0.001
	Comments	One-sided P-value for non-inferiority
	Method	Nam and Kwon
	Comments	P-value was computed for clustered matched pairs based on Nam and Kwon (2009).

Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-1.05
	Confidence Interval	(1-Sided) 97.5% -0.27
	Estimation Comments	Weighted RD and 1-sided 95% upper CL were computed for clustered matched pairs based on Nam and Kwon (2009).

6.Secondary Outcome


Title	MACCE (Death, Myocardial Infarction or Stroke) - Randomized DES ITT
Description	[Not Specified]
Description	[Not Specified]
Time Frame	21 months (12-33 months post-index procedure)

Outcome Measure Data

Analysis Population Description

All randomized DES ITT patients; Patients were analyzed according to the treatment to which they were randomized (regardless of post-randomization compliance with the randomized treatment); Patients not experiencing the endpoint were censored at 33 months or at last known follow-up, whichever was earlier.


Arm/Group Title	DES 30-month DAPT	DES 12-month DAPT
Arm/Group Description:	Patients who were treated with DES ...	Patients who were treated with DES ...
Arm/Group Description:	Patients who were treated with DES at the index procedure and were randomized at 12 months post procedure to receive a total of 30 months of DAPT	Patients who were treated with DES at the index procedure and were randomized at 12 months post procedure to receive a total of 12 months of DAPT
Overall Number of Participants Analyzed	5020	4941
Measure Type: Number Unit of Measure: percentage of patients (KM estimate)
	5.62	6.49

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DES 30-month DAPT, DES 12-month DAPT
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.82
	Confidence Interval	(2-Sided) 95% 0.70 to 0.97
	Estimation Comments	30-month DAPT vs. 12-month DAPT; HR was stratified according to geographic region (NA, EU, or AU and NZ), thienopyridine drug received at the time of randomization, and presence or absence of risk factors for stent thrombosis

7.Secondary Outcome


Title	Definite or Probable Stent Thrombosis (ST) - Randomized DES ITT
Description	ST was assessed according to the Academic Research Consortium (ARC) de...
Description	ST was assessed according to the Academic Research Consortium (ARC) definitions.
Time Frame	21 months (12-33 months post-index procedure)

Outcome Measure Data

Analysis Population Description

All randomized DES ITT patients; Patients were analyzed according to the treatment to which they were randomized (regardless of post-randomization compliance with the randomized treatment); Patients not experiencing the endpoint were censored at 33 months or at last known follow-up, whichever was earlier.


Arm/Group Title	DES 30-month DAPT	DES 12-month DAPT
Arm/Group Description:	Patients who were treated with DES ...	Patients who were treated with DES ...
Arm/Group Description:	Patients who were treated with DES at the index procedure and were randomized at 12 months post procedure to receive a total of 30 months of DAPT	Patients who were treated with DES at the index procedure and were randomized at 12 months post procedure to receive a total of 12 months of DAPT
Overall Number of Participants Analyzed	5020	4941
Measure Type: Number Unit of Measure: percentage of patients (KM estimate)
	0.69	1.45

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DES 30-month DAPT, DES 12-month DAPT
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.45
	Confidence Interval	(2-Sided) 95% 0.29 to 0.69
	Estimation Comments	30-month DAPT vs. 12-month DAPT; HR was stratified according to geographic region (NA, EU, or AU and NZ), thienopyridine drug received at the time of randomization, and presence or absence of risk factors for stent thrombosis

8.Secondary Outcome


Title	GUSTO Severe or Moderate Bleeding - Randomized DES ITT
Description	Bleeding was assessed according to the Global Utilization of Streptoki...
Description	Bleeding was assessed according to the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Arteries (GUSTO) criteria.
Time Frame	21 months (12-33 months post-index procedure)

Outcome Measure Data

Analysis Population Description

Only patients who could be evaluated were included in this analysis (i.e., patients whose last contact date was ≥600 days after randomization or who had any adjudicated bleeding event at or before 630 days).


Arm/Group Title	DES 30-month DAPT	DES 12-month DAPT
Arm/Group Description:	Patients who were treated with DES ...	Patients who were treated with DES ...
Arm/Group Description:	Patients who were treated with DES at the index procedure and were randomized at 12 months post procedure to receive a total of 30 months of DAPT	Patients who were treated with DES at the index procedure and were randomized at 12 months post procedure to receive a total of 12 months of DAPT
Overall Number of Participants Analyzed	4525	4476
Measure Type: Number Unit of Measure: percentage of patients
	2.74	1.88

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DES 30-month DAPT, DES 12-month DAPT
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	0.86
	Confidence Interval	(2-Sided) 95% 0.24 to 1.48
	Estimation Comments	30-month DAPT vs. 12-month DAPT

9.Secondary Outcome


Title	MACCE (Death, Myocardial Infarction or Stroke) - Randomized BMS ITT
Description	[Not Specified]
Description	[Not Specified]
Time Frame	18 months (12-30 months post-index procedure)

Outcome Measure Data

Analysis Population Description

All randomized BMS ITT patients; Patients were analyzed according to the treatment to which they were randomized (regardless of post-randomization compliance with the randomized treatment); Patients not experiencing the endpoint were censored at 30 months or at last known follow-up, whichever was earlier.


Arm/Group Title	BMS 30-month DAPT	BMS 12-month DAPT
Arm/Group Description:	Patients who were treated with BMS ...	Patients who were treated with BMS ...
Arm/Group Description:	Patients who were treated with BMS at the index procedure and were randomized at 12 months post procedure to receive a total of 30 months of DAPT	Patients who were treated with BMS at the index procedure and were randomized at 12 months post procedure to receive a total of 12 months of DAPT
Overall Number of Participants Analyzed	842	845
Measure Type: Number Unit of Measure: percentage of patients (KM estimate)
	4.04	4.69

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	BMS 30-month DAPT, BMS 12-month DAPT
	Comments	This analysis was not powered.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.722
	Comments	This analysis was not powered. P-value was stratified according to geographic region, thienopyridine received at the time of randomization, and presence or absence of risk factors for ST; P-value was adjudsted using the Benjamini Hochberg approach.
	Method	Log Rank
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.92
	Confidence Interval	(2-Sided) 95% 0.57 to 1.47
	Estimation Comments	30-month DAPT vs. 12-month DAPT; HR was stratified according to geographic region (NA, EU, or AU and NZ), thienopyridine drug received at the time of randomization, and presence or absence of risk factors for stent thrombosis.

10.Secondary Outcome


Title	Definite or Probable Stent Thrombosis (ST) - Randomized BMS ITT
Description	ST was assessed according to the Academic Research Consortium (ARC) de...
Description	ST was assessed according to the Academic Research Consortium (ARC) definitions.
Time Frame	18 months (12-30 months post-index procedure)

Outcome Measure Data

Analysis Population Description


Arm/Group Title	BMS 30-month DAPT	BMS 12-month DAPT
Arm/Group Description:	Patients who were treated with BMS ...	Patients who were treated with BMS ...
Arm/Group Description:	Patients who were treated with BMS at the index procedure and were randomized at 12 months post procedure to receive a total of 30 months of DAPT	Patients who were treated with BMS at the index procedure and were randomized at 12 months post procedure to receive a total of 12 months of DAPT
Overall Number of Participants Analyzed	842	845
Measure Type: Number Unit of Measure: percentage of patients (KM estimate)
	0.50	1.11

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	BMS 30-month DAPT, BMS 12-month DAPT
	Comments	This analysis was not powered.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.478
	Comments	This analysis was not powered. P-value was stratified according to geographic region, thienopyridine received at the time of randomization, and presence or absence of risk factors for ST; P-value was adjudsted using the Benjamini Hochberg approach.
	Method	Log Rank
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.49
	Confidence Interval	(2-Sided) 95% 0.15 to 1.64
	Estimation Comments	30-month DAPT vs. 12-month DAPT; HR was stratified according to geographic region (NA, EU, or AU and NZ), thienopyridine drug received at the time of randomization, and presence or absence of risk factors for stent thrombosis.

11.Secondary Outcome


Title	GUSTO Severe or Moderate Bleeding - Randomized BMS ITT
Description	Bleeding was assessed according to the Global Utilization of Streptoki...
Description	Bleeding was assessed according to the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Arteries (GUSTO) criteria.
Time Frame	18 months (12-30 months post-index procedure)

Outcome Measure Data

Analysis Population Description


Arm/Group Title	BMS 30-month DAPT	BMS 12-month DAPT
Arm/Group Description:	Patients who were treated with BMS ...	Patients who were treated with BMS ...
Arm/Group Description:	Patients who were treated with BMS at the index procedure and were randomized at 12 months post procedure to receive a total of 30 months of DAPT	Patients who were treated with BMS at the index procedure and were randomized at 12 months post procedure to receive a total of 12 months of DAPT
Overall Number of Participants Analyzed	790	776
Measure Type: Number Unit of Measure: percentage of patients
	2.03	0.90

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	BMS 30-month DAPT, BMS 12-month DAPT
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.706
	Comments	[Not Specified]
	Method	Farrington-Manning
	Comments	No formal hypothesis testing was done.

Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	1.12
	Confidence Interval	(2-Sided) 95% -0.06 to 2.31
	Estimation Comments	30-month DAPT vs. 12-month DAPT

12.Secondary Outcome


Title	MACCE (Death, Myocardial Infarction or Stroke) - Randomized BMS ITT
Description	[Not Specified]
Description	[Not Specified]
Time Frame	21 months (12-33 months post-index procedure)

Outcome Measure Data

Analysis Population Description

All randomized BMS ITT patients; Patients were analyzed according to the treatment to which they were randomized (regardless of post-randomization compliance with the randomized treatment); Patients not experiencing the endpoint were censored at 33 months or at last known follow-up, whichever was earlier.


Arm/Group Title	BMS 30-month DAPT	BMS 12-month DAPT
Arm/Group Description:	Patients who were treated with BMS ...	Patients who were treated with BMS ...
Arm/Group Description:	Patients who were treated with BMS at the index procedure and were randomized at 12 months post procedure to receive a total of 30 months of DAPT	Patients who were treated with BMS at the index procedure and were randomized at 12 months post procedure to receive a total of 12 months of DAPT
Overall Number of Participants Analyzed	842	845
Measure Type: Number Unit of Measure: percentage of patients (KM estimate)
	4.68	5.48

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	BMS 30-month DAPT, BMS 12-month DAPT
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.91
	Confidence Interval	(2-Sided) 95% 0.58 to 1.40
	Estimation Comments	30-month DAPT vs. 12-month DAPT; HR was stratified according to geographic region (NA, EU, or AU and NZ), thienopyridine drug received at the time of randomization, and presence or absence of risk factors for stent thrombosis

13.Secondary Outcome


Title	Definite or Probable Stent Thrombosis (ST) - Randomized BMS ITT
Description	ST was assessed according to the Academic Research Consortium (ARC) de...
Description	ST was assessed according to the Academic Research Consortium (ARC) definitions.
Time Frame	21 months (12-33 months post-index procedure)

Outcome Measure Data

Analysis Population Description

All randomized BMS ITT patients; Patients were analyzed according to the treatment to which they were randomized (regardless of post-randomization compliance with the randomized treatment); Patients not experiencing the endpoint were censored at 33 months or at last known follow-up, whichever was earlier.


Arm/Group Title	BMS 30-month DAPT	BMS 12-month DAPT
Arm/Group Description:	Patients who were treated with BMS ...	Patients who were treated with BMS ...
Arm/Group Description:	Patients who were treated with BMS at the index procedure and were randomized at 12 months post procedure to receive a total of 30 months of DAPT	Patients who were treated with BMS at the index procedure and were randomized at 12 months post procedure to receive a total of 12 months of DAPT
Overall Number of Participants Analyzed	842	845
Measure Type: Number Unit of Measure: percentage of patients (KM estimate)
	0.50	1.11

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	BMS 30-month DAPT, BMS 12-month DAPT
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.49
	Confidence Interval	(2-Sided) 95% 0.15 to 1.64
	Estimation Comments	30-month DAPT vs. 12-month DAPT; HR was stratified according to geographic region (NA, EU, or AU and NZ), thienopyridine drug received at the time of randomization, and presence or absence of risk factors for stent thrombosis.

14.Secondary Outcome


Title	GUSTO Severe or Moderate Bleeding - Randomized BMS ITT
Description	Bleeding was assessed according to the Global Utilization of Streptoki...
Description	Bleeding was assessed according to the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Arteries (GUSTO) criteria.
Time Frame	21 months (12-33 months post-index procedure)

Outcome Measure Data

Analysis Population Description


Arm/Group Title	BMS 30-month DAPT	BMS 12-month DAPT
Arm/Group Description:	Patients who were treated with BMS ...	Patients who were treated with BMS ...
Arm/Group Description:	Patients who were treated with BMS at the index procedure and were randomized at 12 months post procedure to receive a total of 30 months of DAPT	Patients who were treated with BMS at the index procedure and were randomized at 12 months post procedure to receive a total of 12 months of DAPT
Overall Number of Participants Analyzed	766	759
Measure Type: Number Unit of Measure: percentage of patients
	2.09	1.05

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	BMS 30-month DAPT, BMS 12-month DAPT
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	1.03
	Confidence Interval	(2-Sided) 95% -0.21 to 2.28
	Estimation Comments	30-month DAPT vs. 12-month DAPT

Adverse Events

Time Frame	12-33 months post-index procedure (randomization to 33 months post-index procedure)
Adverse Event Reporting Description	[Not Specified]

Arm/Group Title	HCRI DAPT - DES 30-month DAPT		HCRI DAPT - DES 12-month DAPT		HCRI DAPT - BMS 30-month DAPT		HCRI DAPT - BMS 12-month DAPT
Arm/Group Description	Patients who were enrolled by HCRI ...		Patients who were enrolled by HCRI ...		Patients who were enrolled by HCRI ...		Patients who were enrolled by HCRI ...
Arm/Group Description	Patients who were enrolled by HCRI into the HCRI DAPT Study, treated with DES at the index procedure and randomized at 12 months post procedure to receive a total of 30 months of DAPT		Patients who were enrolled by HCRI into the HCRI DAPT Study, treated with DES at the index procedure and randomized at 12 months post procedure to receive a total of 12 months of DAPT		Patients who were enrolled by HCRI into the HCRI DAPT Study, treated with BMS at the index procedure and randomized at 12 months post procedure to receive a total of 30 months of DAPT		Patients who were enrolled by HCRI into the HCRI DAPT Study, treated with BMS at the index procedure and randomized at 12 months post procedure to receive a total of 12 months of DAPT
All-Cause Mortality
	HCRI DAPT - DES 30-month DAPT		HCRI DAPT - DES 12-month DAPT		HCRI DAPT - BMS 30-month DAPT		HCRI DAPT - BMS 12-month DAPT
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--		--/--		--/--
Serious Adverse Events Serious Adverse Events
	HCRI DAPT - DES 30-month DAPT		HCRI DAPT - DES 12-month DAPT		HCRI DAPT - BMS 30-month DAPT		HCRI DAPT - BMS 12-month DAPT
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	617/2642 (23.35%)		572/2634 (21.72%)		144/842 (17.10%)		150/845 (17.75%)
Blood and lymphatic system disorders
ANAEMIA	12/2642 (0.45%)		9/2634 (0.34%)		1/842 (0.12%)		1/845 (0.12%)
ANAEMIA OF CHRONIC DISEASE	2/2642 (0.08%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
COAGULOPATHY	0/2642 (0.00%)		0/2634 (0.00%)		0/842 (0.00%)		1/845 (0.12%)
IRON DEFICIENCY ANAEMIA	1/2642 (0.04%)		3/2634 (0.11%)		1/842 (0.12%)		0/845 (0.00%)
RETROPERITONEAL LYMPHADENOPATHY	0/2642 (0.00%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
SPLENIC INFARCTION	0/2642 (0.00%)		0/2634 (0.00%)		1/842 (0.12%)		0/845 (0.00%)
THROMBOCYTOPENIA	1/2642 (0.04%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
Cardiac disorders
ACUTE CORONARY SYNDROME	0/2642 (0.00%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
ANGINA PECTORIS	55/2642 (2.08%)		55/2634 (2.09%)		13/842 (1.54%)		18/845 (2.13%)
ANGINA UNSTABLE	27/2642 (1.02%)		40/2634 (1.52%)		4/842 (0.48%)		5/845 (0.59%)
AORTIC VALVE INCOMPETENCE	0/2642 (0.00%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
ARRHYTHMIA	3/2642 (0.11%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
ARTERIOSCLEROSIS CORONARY ARTERY	1/2642 (0.04%)		0/2634 (0.00%)		0/842 (0.00%)		1/845 (0.12%)
ARTERIOSPASM CORONARY	0/2642 (0.00%)		1/2634 (0.04%)		1/842 (0.12%)		0/845 (0.00%)
ATRIAL FIBRILLATION	24/2642 (0.91%)		14/2634 (0.53%)		3/842 (0.36%)		9/845 (1.07%)
ATRIAL FLUTTER	2/2642 (0.08%)		6/2634 (0.23%)		1/842 (0.12%)		0/845 (0.00%)
ATRIAL TACHYCARDIA	1/2642 (0.04%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
ATRIOVENTRICULAR BLOCK	0/2642 (0.00%)		1/2634 (0.04%)		0/842 (0.00%)		1/845 (0.12%)
ATRIOVENTRICULAR BLOCK COMPLETE	1/2642 (0.04%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
BRADYCARDIA	2/2642 (0.08%)		5/2634 (0.19%)		1/842 (0.12%)		2/845 (0.24%)
BUNDLE BRANCH BLOCK LEFT	0/2642 (0.00%)		0/2634 (0.00%)		0/842 (0.00%)		1/845 (0.12%)
CARDIAC ARREST	8/2642 (0.30%)		9/2634 (0.34%)		2/842 (0.24%)		0/845 (0.00%)
CARDIAC DISORDER	0/2642 (0.00%)		0/2634 (0.00%)		1/842 (0.12%)		1/845 (0.12%)
CARDIAC FAILURE	5/2642 (0.19%)		7/2634 (0.27%)		2/842 (0.24%)		1/845 (0.12%)
CARDIAC FAILURE ACUTE	0/2642 (0.00%)		1/2634 (0.04%)		2/842 (0.24%)		1/845 (0.12%)
CARDIAC FAILURE CONGESTIVE	22/2642 (0.83%)		14/2634 (0.53%)		4/842 (0.48%)		5/845 (0.59%)
CARDIO-RESPIRATORY ARREST	0/2642 (0.00%)		2/2634 (0.08%)		1/842 (0.12%)		1/845 (0.12%)
CARDIOGENIC SHOCK	1/2642 (0.04%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
CARDIOMYOPATHY	1/2642 (0.04%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
CARDIOPULMONARY FAILURE	1/2642 (0.04%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
CONGESTIVE CARDIOMYOPATHY	1/2642 (0.04%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
CORONARY ARTERY DISEASE	22/2642 (0.83%)		16/2634 (0.61%)		9/842 (1.07%)		6/845 (0.71%)
CORONARY ARTERY DISSECTION	0/2642 (0.00%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
CORONARY ARTERY OCCLUSION	2/2642 (0.08%)		1/2634 (0.04%)		1/842 (0.12%)		0/845 (0.00%)
CORONARY ARTERY STENOSIS	5/2642 (0.19%)		7/2634 (0.27%)		0/842 (0.00%)		1/845 (0.12%)
EXTRASYSTOLES	1/2642 (0.04%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
ISCHAEMIC CARDIOMYOPATHY	2/2642 (0.08%)		0/2634 (0.00%)		1/842 (0.12%)		1/845 (0.12%)
LEFT VENTRICULAR DYSFUNCTION	1/2642 (0.04%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
LEFT VENTRICULAR FAILURE	0/2642 (0.00%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
MITRAL VALVE INCOMPETENCE	1/2642 (0.04%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
MYOCARDIAL ISCHAEMIA	2/2642 (0.08%)		1/2634 (0.04%)		0/842 (0.00%)		5/845 (0.59%)
PALPITATIONS	1/2642 (0.04%)		4/2634 (0.15%)		0/842 (0.00%)		0/845 (0.00%)
PERICARDIAL EFFUSION	1/2642 (0.04%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
PERICARDITIS	1/2642 (0.04%)		1/2634 (0.04%)		1/842 (0.12%)		0/845 (0.00%)
SICK SINUS SYNDROME	2/2642 (0.08%)		0/2634 (0.00%)		2/842 (0.24%)		1/845 (0.12%)
SUBENDOCARDIAL ISCHAEMIA	0/2642 (0.00%)		0/2634 (0.00%)		0/842 (0.00%)		1/845 (0.12%)
SUPRAVENTRICULAR EXTRASYSTOLES	0/2642 (0.00%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
SUPRAVENTRICULAR TACHYCARDIA	4/2642 (0.15%)		2/2634 (0.08%)		0/842 (0.00%)		2/845 (0.24%)
TACHYCARDIA	1/2642 (0.04%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
VENTRICULAR FIBRILLATION	1/2642 (0.04%)		2/2634 (0.08%)		0/842 (0.00%)		0/845 (0.00%)
VENTRICULAR TACHYCARDIA	0/2642 (0.00%)		4/2634 (0.15%)		0/842 (0.00%)		1/845 (0.12%)
Congenital, familial and genetic disorders
ARTERIOVENOUS MALFORMATION	1/2642 (0.04%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
ATRIAL SEPTAL DEFECT	1/2642 (0.04%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
HYDROCELE	1/2642 (0.04%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
MYOTONIC DYSTROPHY	1/2642 (0.04%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
Ear and labyrinth disorders
EXOSTOSIS OF EXTERNAL EAR CANAL	0/2642 (0.00%)		0/2634 (0.00%)		1/842 (0.12%)		0/845 (0.00%)
MENIERE'S DISEASE	0/2642 (0.00%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
VERTIGO	2/2642 (0.08%)		5/2634 (0.19%)		0/842 (0.00%)		0/845 (0.00%)
Endocrine disorders
HYPERPARATHYROIDISM	0/2642 (0.00%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
HYPOTHYROIDISM	1/2642 (0.04%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
INAPPROPRIATE ANTIDIURETIC HORMONE SECRETION	0/2642 (0.00%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
THYROID MASS	0/2642 (0.00%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
Eye disorders
CATARACT	2/2642 (0.08%)		0/2634 (0.00%)		1/842 (0.12%)		0/845 (0.00%)
EYE PAIN	0/2642 (0.00%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
GLAUCOMA	0/2642 (0.00%)		0/2634 (0.00%)		0/842 (0.00%)		1/845 (0.12%)
MACULAR DEGENERATION	0/2642 (0.00%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
RETINAL DETACHMENT	0/2642 (0.00%)		1/2634 (0.04%)		1/842 (0.12%)		0/845 (0.00%)
RETINAL HAEMORRHAGE	0/2642 (0.00%)		0/2634 (0.00%)		0/842 (0.00%)		1/845 (0.12%)
VISUAL ACUITY REDUCED	2/2642 (0.08%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
Gastrointestinal disorders
ABDOMINAL HERNIA	0/2642 (0.00%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
ABDOMINAL PAIN	3/2642 (0.11%)		1/2634 (0.04%)		1/842 (0.12%)		3/845 (0.36%)
ABDOMINAL PAIN LOWER	1/2642 (0.04%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
ABDOMINAL PAIN UPPER	1/2642 (0.04%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
APHTHOUS STOMATITIS	1/2642 (0.04%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
ASCITES	1/2642 (0.04%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
COLITIS	1/2642 (0.04%)		2/2634 (0.08%)		0/842 (0.00%)		1/845 (0.12%)
COLITIS ISCHAEMIC	2/2642 (0.08%)		1/2634 (0.04%)		1/842 (0.12%)		0/845 (0.00%)
COLITIS ULCERATIVE	0/2642 (0.00%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
CROHN'S DISEASE	2/2642 (0.08%)		0/2634 (0.00%)		1/842 (0.12%)		0/845 (0.00%)
DIARRHOEA	2/2642 (0.08%)		1/2634 (0.04%)		2/842 (0.24%)		1/845 (0.12%)
DIVERTICULAR PERFORATION	1/2642 (0.04%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
DIVERTICULUM	0/2642 (0.00%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
DIVERTICULUM INTESTINAL HAEMORRHAGIC	1/2642 (0.04%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
DUODENITIS	1/2642 (0.04%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
EPIPLOIC APPENDAGITIS	1/2642 (0.04%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
GASTRIC ULCER	1/2642 (0.04%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
GASTRITIS	2/2642 (0.08%)		0/2634 (0.00%)		1/842 (0.12%)		0/845 (0.00%)
GASTRITIS EROSIVE	1/2642 (0.04%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
GASTROINTESTINAL HAEMORRHAGE	10/2642 (0.38%)		2/2634 (0.08%)		0/842 (0.00%)		0/845 (0.00%)
GASTROINTESTINAL PAIN	0/2642 (0.00%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
GASTROOESOPHAGEAL REFLUX DISEASE	0/2642 (0.00%)		2/2634 (0.08%)		3/842 (0.36%)		1/845 (0.12%)
HAEMATOCHEZIA	0/2642 (0.00%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
HAEMORRHOIDAL HAEMORRHAGE	1/2642 (0.04%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
HAEMORRHOIDS	0/2642 (0.00%)		2/2634 (0.08%)		0/842 (0.00%)		0/845 (0.00%)
HIATUS HERNIA	0/2642 (0.00%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
IMPAIRED GASTRIC EMPTYING	0/2642 (0.00%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
INGUINAL HERNIA	3/2642 (0.11%)		3/2634 (0.11%)		2/842 (0.24%)		2/845 (0.24%)
INGUINAL HERNIA, OBSTRUCTIVE	0/2642 (0.00%)		0/2634 (0.00%)		0/842 (0.00%)		1/845 (0.12%)
INTESTINAL ISCHAEMIA	0/2642 (0.00%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
INTESTINAL OBSTRUCTION	0/2642 (0.00%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
LARGE INTESTINE PERFORATION	1/2642 (0.04%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
LOWER GASTROINTESTINAL HAEMORRHAGE	0/2642 (0.00%)		0/2634 (0.00%)		1/842 (0.12%)		0/845 (0.00%)
MELAENA	1/2642 (0.04%)		0/2634 (0.00%)		1/842 (0.12%)		1/845 (0.12%)
NAUSEA	1/2642 (0.04%)		0/2634 (0.00%)		0/842 (0.00%)		2/845 (0.24%)
OESOPHAGEAL PERFORATION	0/2642 (0.00%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
OESOPHAGEAL SPASM	0/2642 (0.00%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
OESOPHAGITIS	1/2642 (0.04%)		0/2634 (0.00%)		0/842 (0.00%)		1/845 (0.12%)
PANCREATIC MASS	0/2642 (0.00%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
PANCREATIC PSEUDOCYST	0/2642 (0.00%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
PANCREATITIS	2/2642 (0.08%)		2/2634 (0.08%)		1/842 (0.12%)		1/845 (0.12%)
PANCREATITIS ACUTE	3/2642 (0.11%)		3/2634 (0.11%)		0/842 (0.00%)		1/845 (0.12%)
PHARYNGOESOPHAGEAL DIVERTICULUM	1/2642 (0.04%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
POLYP COLORECTAL	0/2642 (0.00%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
RECTAL HAEMORRHAGE	1/2642 (0.04%)		1/2634 (0.04%)		1/842 (0.12%)		0/845 (0.00%)
RECTAL POLYP	1/2642 (0.04%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
SMALL INTESTINAL OBSTRUCTION	1/2642 (0.04%)		5/2634 (0.19%)		1/842 (0.12%)		0/845 (0.00%)
SPIGELIAN HERNIA	1/2642 (0.04%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
UMBILICAL HERNIA	2/2642 (0.08%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
UPPER GASTROINTESTINAL HAEMORRHAGE	0/2642 (0.00%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
VOLVULUS	0/2642 (0.00%)		0/2634 (0.00%)		0/842 (0.00%)		1/845 (0.12%)
VOMITING	0/2642 (0.00%)		0/2634 (0.00%)		1/842 (0.12%)		1/845 (0.12%)
General disorders
ADVERSE DRUG REACTION	0/2642 (0.00%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
ASTHENIA	1/2642 (0.04%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
CHEST DISCOMFORT	8/2642 (0.30%)		4/2634 (0.15%)		0/842 (0.00%)		1/845 (0.12%)
CHEST PAIN	43/2642 (1.63%)		45/2634 (1.71%)		12/842 (1.43%)		7/845 (0.83%)
DEATH	1/2642 (0.04%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
HERNIA	1/2642 (0.04%)		0/2634 (0.00%)		2/842 (0.24%)		0/845 (0.00%)
HERNIA OBSTRUCTIVE	0/2642 (0.00%)		2/2634 (0.08%)		1/842 (0.12%)		0/845 (0.00%)
NON-CARDIAC CHEST PAIN	54/2642 (2.04%)		51/2634 (1.94%)		12/842 (1.43%)		15/845 (1.78%)
OEDEMA PERIPHERAL	1/2642 (0.04%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
PAIN	4/2642 (0.15%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
PELVIC MASS	0/2642 (0.00%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
PYREXIA	1/2642 (0.04%)		1/2634 (0.04%)		1/842 (0.12%)		0/845 (0.00%)
SWELLING	3/2642 (0.11%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
SYSTEMIC INFLAMMATORY RESPONSE SYNDROME	1/2642 (0.04%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
Hepatobiliary disorders
ALCOHOLIC LIVER DISEASE	1/2642 (0.04%)		0/2634 (0.00%)		0/842 (0.00%)		1/845 (0.12%)
BILE DUCT OBSTRUCTION	1/2642 (0.04%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
BILE DUCT STENOSIS	0/2642 (0.00%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
BILE DUCT STONE	0/2642 (0.00%)		0/2634 (0.00%)		0/842 (0.00%)		1/845 (0.12%)
BILIARY COLIC	0/2642 (0.00%)		2/2634 (0.08%)		0/842 (0.00%)		0/845 (0.00%)
CHOLANGITIS	1/2642 (0.04%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
CHOLECYSTITIS	5/2642 (0.19%)		2/2634 (0.08%)		0/842 (0.00%)		0/845 (0.00%)
CHOLECYSTITIS ACUTE	7/2642 (0.26%)		7/2634 (0.27%)		0/842 (0.00%)		0/845 (0.00%)
CHOLELITHIASIS	2/2642 (0.08%)		3/2634 (0.11%)		0/842 (0.00%)		1/845 (0.12%)
CHOLESTASIS	1/2642 (0.04%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
CHRONIC HEPATIC FAILURE	1/2642 (0.04%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
HEPATIC CIRRHOSIS	1/2642 (0.04%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
Immune system disorders
ALLERGY TO METALS	0/2642 (0.00%)		0/2634 (0.00%)		0/842 (0.00%)		1/845 (0.12%)
Infections and infestations
ABDOMINAL WALL ABSCESS	0/2642 (0.00%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
ABSCESS	0/2642 (0.00%)		2/2634 (0.08%)		0/842 (0.00%)		1/845 (0.12%)
ABSCESS LIMB	1/2642 (0.04%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
ANAL ABSCESS	1/2642 (0.04%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
APPENDICITIS	7/2642 (0.26%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
APPENDICITIS PERFORATED	1/2642 (0.04%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
ARTERIOVENOUS GRAFT SITE INFECTION	1/2642 (0.04%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
BACTERAEMIA	2/2642 (0.08%)		1/2634 (0.04%)		1/842 (0.12%)		0/845 (0.00%)
BRONCHIECTASIS	1/2642 (0.04%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
BRONCHITIS	5/2642 (0.19%)		5/2634 (0.19%)		2/842 (0.24%)		0/845 (0.00%)
BRONCHITIS BACTERIAL	1/2642 (0.04%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
BRONCHOPNEUMONIA	2/2642 (0.08%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
CAMPYLOBACTER INTESTINAL INFECTION	1/2642 (0.04%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
CELLULITIS	8/2642 (0.30%)		9/2634 (0.34%)		1/842 (0.12%)		2/845 (0.24%)
CELLULITIS STAPHYLOCOCCAL	0/2642 (0.00%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
CHOLECYSTITIS INFECTIVE	0/2642 (0.00%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
CLOSTRIDIAL INFECTION	0/2642 (0.00%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
CLOSTRIDIUM DIFFICILE COLITIS	2/2642 (0.08%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
DIVERTICULITIS	6/2642 (0.23%)		6/2634 (0.23%)		1/842 (0.12%)		3/845 (0.36%)
ERYSIPELAS	0/2642 (0.00%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
ESCHERICHIA URINARY TRACT INFECTION	1/2642 (0.04%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
GALLBLADDER ABSCESS	0/2642 (0.00%)		0/2634 (0.00%)		1/842 (0.12%)		0/845 (0.00%)
GANGRENE	2/2642 (0.08%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
GASTRIC INFECTION	1/2642 (0.04%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
GASTROENTERITIS	3/2642 (0.11%)		2/2634 (0.08%)		0/842 (0.00%)		1/845 (0.12%)
GASTROENTERITIS VIRAL	2/2642 (0.08%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
GIARDIASIS	1/2642 (0.04%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
INFECTION	2/2642 (0.08%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
INFLUENZA	2/2642 (0.08%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
INTERVERTEBRAL DISCITIS	1/2642 (0.04%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
LOBAR PNEUMONIA	2/2642 (0.08%)		2/2634 (0.08%)		0/842 (0.00%)		0/845 (0.00%)
MASTOIDITIS	1/2642 (0.04%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
MENINGITIS ASEPTIC	1/2642 (0.04%)		0/2634 (0.00%)		0/842 (0.00%)		1/845 (0.12%)
NEUTROPENIC SEPSIS	1/2642 (0.04%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
OSTEOMYELITIS	2/2642 (0.08%)		2/2634 (0.08%)		0/842 (0.00%)		0/845 (0.00%)
PANCREATIC ABSCESS	0/2642 (0.00%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
PHARYNGITIS	0/2642 (0.00%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
PILONIDAL CYST	0/2642 (0.00%)		0/2634 (0.00%)		1/842 (0.12%)		0/845 (0.00%)
PNEUMONIA	21/2642 (0.79%)		17/2634 (0.65%)		4/842 (0.48%)		4/845 (0.47%)
POSTOPERATIVE WOUND INFECTION	2/2642 (0.08%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
PSEUDOMONAL SEPSIS	1/2642 (0.04%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
PSEUDOMONAS INFECTION	1/2642 (0.04%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
PYELONEPHRITIS	3/2642 (0.11%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
PYELONEPHRITIS ACUTE	1/2642 (0.04%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
SEPSIS	9/2642 (0.34%)		7/2634 (0.27%)		1/842 (0.12%)		0/845 (0.00%)
SEPSIS SYNDROME	0/2642 (0.00%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
SINUSITIS	0/2642 (0.00%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
STAPHYLOCOCCAL BACTERAEMIA	0/2642 (0.00%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
STAPHYLOCOCCAL INFECTION	1/2642 (0.04%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
STITCH ABSCESS	1/2642 (0.04%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
UPPER RESPIRATORY TRACT INFECTION	0/2642 (0.00%)		0/2634 (0.00%)		0/842 (0.00%)		1/845 (0.12%)
URINARY TRACT INFECTION	5/2642 (0.19%)		7/2634 (0.27%)		2/842 (0.24%)		1/845 (0.12%)
UROSEPSIS	3/2642 (0.11%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
VIRAL INFECTION	0/2642 (0.00%)		3/2634 (0.11%)		0/842 (0.00%)		0/845 (0.00%)
WOUND INFECTION	1/2642 (0.04%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
Injury, poisoning and procedural complications
BURNS THIRD DEGREE	1/2642 (0.04%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
CARTILAGE INJURY	1/2642 (0.04%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
CERVICAL VERTEBRAL FRACTURE	1/2642 (0.04%)		3/2634 (0.11%)		0/842 (0.00%)		0/845 (0.00%)
CLAVICLE FRACTURE	0/2642 (0.00%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
COLLAPSE OF LUNG	0/2642 (0.00%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
COMPRESSION FRACTURE	0/2642 (0.00%)		0/2634 (0.00%)		1/842 (0.12%)		2/845 (0.24%)
CONTUSION	2/2642 (0.08%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
CORONARY ARTERY RESTENOSIS	1/2642 (0.04%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
CYSTITIS RADIATION	0/2642 (0.00%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
DEVICE MALFUNCTION	1/2642 (0.04%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
FALL	4/2642 (0.15%)		2/2634 (0.08%)		0/842 (0.00%)		1/845 (0.12%)
FEMORAL NECK FRACTURE	2/2642 (0.08%)		0/2634 (0.00%)		1/842 (0.12%)		1/845 (0.12%)
FEMUR FRACTURE	1/2642 (0.04%)		2/2634 (0.08%)		0/842 (0.00%)		0/845 (0.00%)
FOOT FRACTURE	1/2642 (0.04%)		1/2634 (0.04%)		1/842 (0.12%)		0/845 (0.00%)
HEAD INJURY	0/2642 (0.00%)		2/2634 (0.08%)		0/842 (0.00%)		0/845 (0.00%)
HEPATIC HAEMATOMA	1/2642 (0.04%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
HIP FRACTURE	1/2642 (0.04%)		3/2634 (0.11%)		2/842 (0.24%)		2/845 (0.24%)
HUMERUS FRACTURE	0/2642 (0.00%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
IN-STENT ARTERIAL RESTENOSIS	3/2642 (0.11%)		0/2634 (0.00%)		2/842 (0.24%)		1/845 (0.12%)
IN-STENT CORONARY ARTERY RESTENOSIS	11/2642 (0.42%)		5/2634 (0.19%)		4/842 (0.48%)		2/845 (0.24%)
INCISIONAL HERNIA	0/2642 (0.00%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
INJURY	3/2642 (0.11%)		1/2634 (0.04%)		1/842 (0.12%)		0/845 (0.00%)
JOINT DISLOCATION	1/2642 (0.04%)		2/2634 (0.08%)		0/842 (0.00%)		0/845 (0.00%)
LACERATION	0/2642 (0.00%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
LIMB INJURY	1/2642 (0.04%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
LOWER LIMB FRACTURE	0/2642 (0.00%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
MENISCUS LESION	1/2642 (0.04%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
MULTIPLE FRACTURES	1/2642 (0.04%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
MUSCLE RUPTURE	0/2642 (0.00%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
OVERDOSE	0/2642 (0.00%)		0/2634 (0.00%)		0/842 (0.00%)		1/845 (0.12%)
POSTOPERATIVE ILEUS	0/2642 (0.00%)		0/2634 (0.00%)		0/842 (0.00%)		1/845 (0.12%)
PUBIC RAMI FRACTURE	1/2642 (0.04%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
RIB FRACTURE	1/2642 (0.04%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
ROAD TRAFFIC ACCIDENT	2/2642 (0.08%)		0/2634 (0.00%)		1/842 (0.12%)		2/845 (0.24%)
SKIN LACERATION	1/2642 (0.04%)		0/2634 (0.00%)		1/842 (0.12%)		1/845 (0.12%)
SPINAL CORD INJURY	1/2642 (0.04%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
SPINAL FRACTURE	1/2642 (0.04%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
SUBDURAL HAEMATOMA	1/2642 (0.04%)		1/2634 (0.04%)		0/842 (0.00%)		1/845 (0.12%)
SUBDURAL HAEMORRHAGE	0/2642 (0.00%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
TENDON INJURY	1/2642 (0.04%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
TENDON RUPTURE	1/2642 (0.04%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
THERMAL BURN	0/2642 (0.00%)		1/2634 (0.04%)		1/842 (0.12%)		0/845 (0.00%)
THORACIC VERTEBRAL FRACTURE	1/2642 (0.04%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
THROMBOSIS IN DEVICE	0/2642 (0.00%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
UPPER LIMB FRACTURE	1/2642 (0.04%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
URETHRAL INJURY	1/2642 (0.04%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
URINARY BLADDER RUPTURE	0/2642 (0.00%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
VASCULAR BYPASS DYSFUNCTION	0/2642 (0.00%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
VASCULAR GRAFT OCCLUSION	0/2642 (0.00%)		0/2634 (0.00%)		1/842 (0.12%)		0/845 (0.00%)
VASCULAR PSEUDOANEURYSM	2/2642 (0.08%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
WOUND DEHISCENCE	2/2642 (0.08%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
Investigations
ANTIMICROBIAL SUSCEPTIBILITY TEST RESISTANT	0/2642 (0.00%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
BLOOD CREATININE	1/2642 (0.04%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
BLOOD GLUCOSE FLUCTUATION	1/2642 (0.04%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
BLOOD POTASSIUM INCREASED	0/2642 (0.00%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
BRONCHOSCOPY	1/2642 (0.04%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
EJECTION FRACTION DECREASED	1/2642 (0.04%)		0/2634 (0.00%)		0/842 (0.00%)		1/845 (0.12%)
PROSTATIC SPECIFIC ANTIGEN INCREASED	1/2642 (0.04%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
TROPONIN I INCREASED	0/2642 (0.00%)		0/2634 (0.00%)		0/842 (0.00%)		1/845 (0.12%)
Metabolism and nutrition disorders
DEHYDRATION	1/2642 (0.04%)		2/2634 (0.08%)		1/842 (0.12%)		0/845 (0.00%)
DIABETES MELLITUS	2/2642 (0.08%)		0/2634 (0.00%)		2/842 (0.24%)		1/845 (0.12%)
DIABETIC FOOT	1/2642 (0.04%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
FAILURE TO THRIVE	1/2642 (0.04%)		1/2634 (0.04%)		1/842 (0.12%)		0/845 (0.00%)
GOUT	0/2642 (0.00%)		0/2634 (0.00%)		1/842 (0.12%)		0/845 (0.00%)
HYPERCALCAEMIA	0/2642 (0.00%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
HYPERGLYCAEMIA	2/2642 (0.08%)		3/2634 (0.11%)		0/842 (0.00%)		0/845 (0.00%)
HYPERKALAEMIA	3/2642 (0.11%)		3/2634 (0.11%)		0/842 (0.00%)		1/845 (0.12%)
HYPOGLYCAEMIA	1/2642 (0.04%)		3/2634 (0.11%)		0/842 (0.00%)		0/845 (0.00%)
HYPOKALAEMIA	0/2642 (0.00%)		2/2634 (0.08%)		0/842 (0.00%)		0/845 (0.00%)
HYPONATRAEMIA	1/2642 (0.04%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
METABOLIC ACIDOSIS	0/2642 (0.00%)		0/2634 (0.00%)		0/842 (0.00%)		1/845 (0.12%)
OBESITY	1/2642 (0.04%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
TYPE 2 DIABETES MELLITUS	1/2642 (0.04%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
Musculoskeletal and connective tissue disorders
ARTHRALGIA	3/2642 (0.11%)		4/2634 (0.15%)		0/842 (0.00%)		0/845 (0.00%)
ARTHRITIS	8/2642 (0.30%)		5/2634 (0.19%)		1/842 (0.12%)		0/845 (0.00%)
ARTHROPATHY	1/2642 (0.04%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
BACK PAIN	3/2642 (0.11%)		5/2634 (0.19%)		1/842 (0.12%)		0/845 (0.00%)
CERVICAL SPINAL STENOSIS	1/2642 (0.04%)		4/2634 (0.15%)		0/842 (0.00%)		0/845 (0.00%)
CHONDROCALCINOSIS PYROPHOSPHATE	0/2642 (0.00%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
COMPARTMENT SYNDROME	0/2642 (0.00%)		0/2634 (0.00%)		1/842 (0.12%)		0/845 (0.00%)
COSTOCHONDRITIS	1/2642 (0.04%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
FLANK PAIN	0/2642 (0.00%)		0/2634 (0.00%)		0/842 (0.00%)		1/845 (0.12%)
FOOT DEFORMITY	1/2642 (0.04%)		0/2634 (0.00%)		1/842 (0.12%)		0/845 (0.00%)
GOUTY ARTHRITIS	1/2642 (0.04%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
HAEMARTHROSIS	1/2642 (0.04%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
INTERVERTEBRAL DISC DEGENERATION	0/2642 (0.00%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
INTERVERTEBRAL DISC DISORDER	2/2642 (0.08%)		1/2634 (0.04%)		1/842 (0.12%)		0/845 (0.00%)
INTERVERTEBRAL DISC PROTRUSION	1/2642 (0.04%)		5/2634 (0.19%)		1/842 (0.12%)		1/845 (0.12%)
LUMBAR SPINAL STENOSIS	7/2642 (0.26%)		7/2634 (0.27%)		0/842 (0.00%)		1/845 (0.12%)
MUSCLE SPASMS	0/2642 (0.00%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
MUSCULAR WEAKNESS	0/2642 (0.00%)		0/2634 (0.00%)		1/842 (0.12%)		0/845 (0.00%)
MUSCULOSKELETAL CHEST PAIN	3/2642 (0.11%)		3/2634 (0.11%)		1/842 (0.12%)		1/845 (0.12%)
MUSCULOSKELETAL PAIN	3/2642 (0.11%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
NECK PAIN	3/2642 (0.11%)		1/2634 (0.04%)		1/842 (0.12%)		0/845 (0.00%)
NEUROPATHIC ARTHROPATHY	1/2642 (0.04%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
OSTEOARTHRITIS	29/2642 (1.10%)		25/2634 (0.95%)		7/842 (0.83%)		5/845 (0.59%)
OSTEOLYSIS	0/2642 (0.00%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
OSTEOPOROSIS	0/2642 (0.00%)		0/2634 (0.00%)		1/842 (0.12%)		0/845 (0.00%)
PAIN IN EXTREMITY	2/2642 (0.08%)		2/2634 (0.08%)		0/842 (0.00%)		0/845 (0.00%)
PAIN IN JAW	1/2642 (0.04%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
RHABDOMYOLYSIS	2/2642 (0.08%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
RHEUMATOID ARTHRITIS	0/2642 (0.00%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
ROTATOR CUFF SYNDROME	2/2642 (0.08%)		1/2634 (0.04%)		0/842 (0.00%)		1/845 (0.12%)
SPINAL COLUMN STENOSIS	1/2642 (0.04%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
SPINAL OSTEOARTHRITIS	2/2642 (0.08%)		3/2634 (0.11%)		1/842 (0.12%)		1/845 (0.12%)
SPONDYLOARTHROPATHY	0/2642 (0.00%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
SPONDYLOLISTHESIS	0/2642 (0.00%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
TENDON DISORDER	0/2642 (0.00%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
ACUTE MYELOID LEUKAEMIA	1/2642 (0.04%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
ADENOCARCINOMA	3/2642 (0.11%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
ADENOCARCINOMA PANCREAS	1/2642 (0.04%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
ANGIOSARCOMA	0/2642 (0.00%)		0/2634 (0.00%)		1/842 (0.12%)		0/845 (0.00%)
B-CELL LYMPHOMA	0/2642 (0.00%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
BASAL CELL CARCINOMA	3/2642 (0.11%)		4/2634 (0.15%)		1/842 (0.12%)		0/845 (0.00%)
BENIGN DUODENAL NEOPLASM	1/2642 (0.04%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
BLADDER CANCER	2/2642 (0.08%)		2/2634 (0.08%)		2/842 (0.24%)		0/845 (0.00%)
BLADDER CANCER RECURRENT	1/2642 (0.04%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
BLADDER TRANSITIONAL CELL CARCINOMA	1/2642 (0.04%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
BRAIN NEOPLASM	2/2642 (0.08%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
BREAST CANCER	4/2642 (0.15%)		4/2634 (0.15%)		0/842 (0.00%)		1/845 (0.12%)
BREAST CANCER STAGE III	0/2642 (0.00%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
CARCINOID TUMOUR OF THE SMALL BOWEL	0/2642 (0.00%)		0/2634 (0.00%)		1/842 (0.12%)		0/845 (0.00%)
CARDIAC MYXOMA	0/2642 (0.00%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
CHRONIC LYMPHOCYTIC LEUKAEMIA	1/2642 (0.04%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
CHRONIC MYELOMONOCYTIC LEUKAEMIA	1/2642 (0.04%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
COLON CANCER	4/2642 (0.15%)		3/2634 (0.11%)		3/842 (0.36%)		1/845 (0.12%)
EXTRANODAL MARGINAL ZONE B-CELL LYMPHOMA (MALT TYPE)	1/2642 (0.04%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
GASTRIC CANCER	1/2642 (0.04%)		0/2634 (0.00%)		0/842 (0.00%)		1/845 (0.12%)
HEPATIC NEOPLASM MALIGNANT	2/2642 (0.08%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
INTRAVASCULAR PAPILLARY ENDOTHELIAL HYPERPLASIA	0/2642 (0.00%)		0/2634 (0.00%)		0/842 (0.00%)		1/845 (0.12%)
LANGERHANS' CELL GRANULOMATOSIS	0/2642 (0.00%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
LENTIGO MALIGNA STAGE UNSPECIFIED	0/2642 (0.00%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
LIP AND/OR ORAL CAVITY CANCER	1/2642 (0.04%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
LIP NEOPLASM MALIGNANT STAGE UNSPECIFIED	0/2642 (0.00%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
LUNG CANCER METASTATIC	1/2642 (0.04%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
LUNG CARCINOMA CELL TYPE UNSPECIFIED RECURRENT	0/2642 (0.00%)		0/2634 (0.00%)		1/842 (0.12%)		0/845 (0.00%)
LUNG NEOPLASM	0/2642 (0.00%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
LUNG NEOPLASM MALIGNANT	5/2642 (0.19%)		2/2634 (0.08%)		1/842 (0.12%)		4/845 (0.47%)
LYMPHOMA	1/2642 (0.04%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
MALIGNANT MELANOMA	0/2642 (0.00%)		2/2634 (0.08%)		0/842 (0.00%)		0/845 (0.00%)
MALIGNANT MELANOMA STAGE II	0/2642 (0.00%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
METASTASES TO BONE	1/2642 (0.04%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
METASTASES TO CENTRAL NERVOUS SYSTEM	1/2642 (0.04%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
METASTATIC NEOPLASM	1/2642 (0.04%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
MULTIPLE MYELOMA	0/2642 (0.00%)		1/2634 (0.04%)		0/842 (0.00%)		1/845 (0.12%)
NEOPLASM MALIGNANT	0/2642 (0.00%)		0/2634 (0.00%)		1/842 (0.12%)		0/845 (0.00%)
NEOPLASM PROSTATE	0/2642 (0.00%)		0/2634 (0.00%)		1/842 (0.12%)		0/845 (0.00%)
NON-HODGKIN'S LYMPHOMA	0/2642 (0.00%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
NON-SMALL CELL LUNG CANCER	2/2642 (0.08%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
NON-SMALL CELL LUNG CANCER STAGE IV	0/2642 (0.00%)		1/2634 (0.04%)		0/842 (0.00%)		0/845 (0.00%)
OESOPHAGEAL ADENOCARCINOMA	0/2642 (0.00%)		0/2634 (0.00%)		0/842 (0.00%)		1/845 (0.12%)
OESOPHAGEAL CARCINOMA	0/2642 (0.00%)		2/2634 (0.08%)		0/842 (0.00%)		0/845 (0.00%)
OVARIAN CANCER METASTATIC	1/2642 (0.04%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
PANCREATIC CARCINOMA	1/2642 (0.04%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
PITUITARY TUMOUR BENIGN	1/2642 (0.04%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
PROSTATE CANCER	13/2642 (0.49%)		10/2634 (0.38%)		0/842 (0.00%)		0/845 (0.00%)
PROSTATE CANCER METASTATIC	1/2642 (0.04%)		0/2634 (0.00%)		0/842 (0.00%)		1/845 (0.12%)
RECTAL CANCER	1/2642 (0.04%)		0/2634 (0.00%)		0/842 (0.00%)		0/845 (0.00%)
RECTOSIGMOID CANCER	0/2642 (0.00%)		0/2634 (0.00%)