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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
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
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
Hide 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
Arm/Group Title DES 30-month DAPT DES 12-month DAPT BMS 30-month DAPT BMS 12-month DAPT Total
Hide 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
Hide 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
1.Primary Outcome
Title MACCE (Death, Myocardial Infarction or Stroke) - Randomized DES ITT
Hide 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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
Show Statistical Analysis 1 Hide 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
Hide 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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
Show Statistical Analysis 1 Hide 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
Hide 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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
Show Statistical Analysis 1 Hide 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
Hide Description Secondary powered endpoint
Time Frame 33 months (0-33 months post-index procedure)
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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
Show Statistical Analysis 1 Hide 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
Hide Description Secondary powered endpoint
Time Frame 33 months (0-33 months post-index procedure)
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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
Show Statistical Analysis 1 Hide 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
Hide Description [Not Specified]
Time Frame 21 months (12-33 months post-index procedure)
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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
Show Statistical Analysis 1 Hide 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
Hide Description ST was assessed according to the Academic Research Consortium (ARC) definitions.
Time Frame 21 months (12-33 months post-index procedure)
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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
Show Statistical Analysis 1 Hide 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
Hide 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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
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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
Hide Description [Not Specified]
Time Frame 18 months (12-30 months post-index procedure)
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Hide 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
Hide 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
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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
Hide Description ST was assessed according to the Academic Research Consortium (ARC) definitions.
Time Frame 18 months (12-30 months post-index procedure)
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Hide 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
Hide 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
Show Statistical Analysis 1 Hide 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
Hide 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)
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Hide 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 BMS 30-month DAPT BMS 12-month DAPT
Hide 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
Show Statistical Analysis 1 Hide 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
Hide Description [Not Specified]
Time Frame 21 months (12-33 months post-index procedure)
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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
Show Statistical Analysis 1 Hide 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
Hide Description ST was assessed according to the Academic Research Consortium (ARC) definitions.
Time Frame 21 months (12-33 months post-index procedure)
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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
Show Statistical Analysis 1 Hide 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
Hide 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide 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 BMS 30-month DAPT BMS 12-month DAPT
Hide 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
Show Statistical Analysis 1 Hide 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
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
Hide 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   --/--      --/--      --/--      --/--    
Show Serious Adverse Events Hide 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%)