Trial to Assess the Effects of Vorapaxar (SCH 530348; MK-5348) in Preventing Heart Attack and Stroke in Particpants With Acute Coronary Syndrome (TRA•CER) (Study P04736)

• Sponsor: Merck Sharp & Dohme LLC (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00527943
• Collaborator: Duke Clinical Research Institute (Other)
• Enrollment: 12,944
• Arms: 2
• Actual Duration (Months): 43

Study Details

Study Description

Brief Summary

The study is designed to determine whether vorapaxar, when added to the existing standard of care (eg, aspirin, clopidogrel) for preventing heart attack and stroke in patients with acute coronary syndrome, will yield additional benefit over the existing standard of care in preventing heart attack and stroke.

The study is also designed to assess risk of bleeding with vorapaxar added to the standard of care versus the standard of care alone.

Condition or Disease	Intervention/Treatment	Phase
Atherosclerosis; Myocardial Ischemia; Myocardial Infarction	Drug: Vorapaxar; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 12944 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of SCH 530348 in Addition to Standard of Care in Subjects With Acute Coronary Syndrome: Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRA•CER)
• Actual Study Start Date: Dec 1, 2007
• Actual Primary Completion Date: Jul 1, 2011
• Actual Study Completion Date: Jul 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Loading oral dose of one 40 mg vorapaxar placebo tablet on Day 1, then one 2.5 mg vorapaxar placebo tablet daily, orally for at least 1 year in addition to current treatment of acute coronary syndrome, which will be continued to be administered as per current stand of care.	Drug: Placebo; oral tablets; matching placebo for vorapaxar; loading and maintenance dosing; once daily for at least 1 year
Experimental: Vorapaxar Loading oral dose of one 40 mg vorapaxar tablet on Day 1, then one 2.5 mg vorapaxar tablet daily, orally for at least 1 year in addition to current treatment of acute coronary syndrome, which will be continued to be administered as per current stand of care.	Drug: Vorapaxar; oral tablets; 40-mg loading dose on first day, followed by 2.5 mg once daily for at least 1 year; Other Names: SCH 530348 MK-5348

Outcome Measures

Primary Outcome Measures

1. Kaplan-Meier Estimate of the Percentage of Participants Who Experienced Cardiovascular Death, Myocardial Infarction, Stroke, Recurrent Ischemia With Re-hospitalization, and/or Urgent Coronary Revascularization Within 2 Years From Randomization [Up to 2 years]

   The time (in days) from study start to the first occurrence of any of the following clinical outcomes was recorded: cardiovascular (CV) death, myocardial infarction (MI), stroke, recurrent ischemia with re-hospitalization (RIR), and/or urgent coronary revascularization (UCR). A Clinical Endpoints Committee (CEC) reviewed and adjudicated each suspected efficacy endpoint event while blinded to treatment. Participants who did not have any endpoint event until last visit or participants who were lost to follow-up and had no event were censored at the time of last available information (last study visit). If a participant had a fatal event that was not part of a specific endpoint for analysis, they were censored at the time of death. The Kaplan-Meier estimate reports the percentage of participants who experienced at least 1 of the components of the primary composite efficacy endpoint within 2 years from randomization.

Secondary Outcome Measures

1. Kaplan-Meier Estimate of the Percentage of Participants Who Experienced Cardiovascular Death, Myocardial Infarction, and/or Stroke Within 2 Years From Randomization [up to 2 years]

   The time (in days) from study start to the first occurrence of any of the following clinical outcomes was recorded: cardiovascular (CV) death, myocardial infarction (MI), and/or stroke. A CEC reviewed and adjudicated each suspected efficacy endpoint event while blinded to treatment. Participants who did not have any endpoint event until last visit or participants who were lost to follow-up and had no event were censored at the time of last available information (last study visit). If a participant had a fatal event that was not part of a specific endpoint for analysis, they were censored at the time of death. The Kaplan-Meier estimate reports the percentage of participants who experienced at least 1 of the components of the secondary composite efficacy endpoint within 2 years from randomization.

2. Kaplan-Meier Estimate of the Percentage of Participants Who Met Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Arteries (GUSTO) Moderate or Severe Bleeding Criteria Within 2 Years From Randomization [Up to 2 years]

   Adverse events were categorized as "bleeding events" if the intensity of the event was other or more than would be normally expected in the given situation (eg, mild nosebleed in a person who does not normally have nosebleeds, greater bruising than expected for a given injury, greater volume of blood loss than expected for a given procedure). The investigator graded the intensity of bleeding events according to the GUSTO cooperative group criteria as follows: Mild , Moderate or Severe and the grading was adjudicated by the CEC. The Kaplan-Meier estimate reports the percentage of participants who experienced GUSTO moderate or severe bleeding within 2 years from randomization.

3. Kaplan-Meier Estimate of the Percentage of Participants Who Experienced Clinically Significant Bleeding Within 2 Years From Randomization [Up to 2 years]

   Adverse events were categorized as "bleeding events" if the intensity of the event was other or more than would be normally expected in the given situation (eg, mild nosebleed in a person who does not normally have nosebleeds, greater bruising than expected for a given injury, greater volume of blood loss than expected for a given procedure). The investigator graded the intensity of bleeding events according to the Thrombolysis in Myocardial Infarction (TIMI) Study Group criteria as major, minor or other. "Clinically Significant Bleeding" was defined as the composite of TIMI Major bleeding, TIMI Minor bleeding, or bleeding that required unplanned medical or surgical treatment or unplanned laboratory evaluation even if it did not meet the criteria for TIMI major or minor bleeding. The Kaplan-Meier estimate reports the percentage of participants who experienced clinically significant bleeding within 2 years from randomization.

4. Kaplan-Meier Estimate of the Percentage of Participants Who Experienced CV Death, MI, Stroke, or UCR Within 2 Years From Randomization [Up to 2 years]

   The time (in days) from study start to the first occurrence of any of the following clinical outcomes was recorded: CV death, MI, stroke, or UCR. A CEC reviewed and adjudicated each suspected efficacy endpoint event while blinded to treatment. Participants who did not have any endpoint event until last visit or participants who were lost to follow-up and had no event were censored at the time of last available information (last study visit). If a participant had a fatal event that was not part of a specific endpoint for analysis, they were censored at the time of death. The Kaplan-Meier estimate reports the percentage of participants who experienced CV death, MI, stroke, or UCR within 2 years from randomization.

5. Kaplan-Meier Estimate of the Percentage of Participants Who Experienced CV Death or MI Within 2 Years From Randomization [Up to 2 years]

   The time (in days) from study start to the first occurrence of any of the following clinical outcomes was recorded: CV death or MI. A CEC reviewed and adjudicated each suspected efficacy endpoint event while blinded to treatment. Participants who did not have any endpoint event until last visit or participants who were lost to follow-up and had no event were censored at the time of last available information (last study visit). If a participant had a fatal event that was not part of a specific endpoint for analysis, they were censored at the time of death. The Kaplan-Meier estimate reports the percentage of participants who experienced CV death or MI within 2 years from randomization.

6. Kaplan-Meier Estimate of the Percentage of Participants Who Experienced All-cause Death, MI, Stroke, RIR, or UCR Within 2 Years From Randomization [Up to 2 years]

   The time (in days) from study start to the first occurrence of any of the following clinical outcomes was recorded: all-cause death, MI, stroke, RIR, or UCR. A CEC reviewed and adjudicated each suspected efficacy endpoint event while blinded to treatment. Participants who did not have any endpoint event until last visit or participants who were lost to follow-up and had no event were censored at the time of last available information (last study visit). The Kaplan-Meier estimate reports the percentage of participants who experienced all-cause death, MI, stroke, RIR, or UCR within 2 years from randomization.

7. Kaplan-Meier Estimate of the Percentage of Participants Who Experienced All-cause Death, MI, Stroke, or UCR Within 2 Years From Randomization [Up to 2 years]

   The time (in days) from study start to the first occurrence of any of the following clinical outcomes was recorded: all-cause death, MI, stroke, or UCR. A CEC reviewed and adjudicated each suspected efficacy endpoint event while blinded to treatment. Participants who did not have any endpoint event until last visit or participants who were lost to follow-up and had no event were censored at the time of last available information (last study visit). The Kaplan-Meier estimate reports the percentage of participants who experienced all-cause Death, MI, stroke, or UCR I within 2 years from randomization.

8. Kaplan-Meier Estimate of the Percentage of Participants Who Experienced CV Death Within 2 Years From Randomization [Up to 2 years]

   The time (in days) from study start to the CV death (if reported) was recorded. A CEC reviewed and adjudicated each suspected efficacy endpoint event while blinded to treatment. Participants who did not have any endpoint event until last visit or participants who were lost to follow-up and had no event were censored at the time of last available information (last study visit). If a participant had a fatal event that was not part of a specific endpoint for analysis, they were censored at the time of death. The Kaplan-Meier estimate reports the percentage of participants who experienced CV death within 2 years from randomization.

9. Kaplan-Meier Estimate of the Percentage of Participants Who Experienced an MI Within 2 Years From Randomization [Up to 2 years]

   The time (in days) from study start to the first occurrence of an MI was recorded. A CEC reviewed and adjudicated each suspected efficacy endpoint event while blinded to treatment. Participants who did not have any endpoint event until last visit or participants who were lost to follow-up and had no event were censored at the time of last available information (last study visit). If a participant had a fatal event that was not part of a specific endpoint for analysis, they were censored at the time of death. The Kaplan-Meier estimate reports the percentage of participants who experienced an MI within 2 years from randomization.

10. Kaplan-Meier Estimate of the Percentage of Participants Who Experienced RIR Within 2 Years From Randomization [Up to 2 years]

    The time (in days) from study start to the first occurrence of RIR was recorded. A CEC reviewed and adjudicated each suspected efficacy endpoint event while blinded to treatment. Participants who did not have any endpoint event until last visit or participants who were lost to follow-up and had no event were censored at the time of last available information (last study visit). If a participant had a fatal event that was not part of a specific endpoint for analysis, they were censored at the time of death. The Kaplan-Meier estimate reports the percentage of participants who experienced RIR within 2 years from randomization.

11. Kaplan-Meier Estimate of the Percentage of Participants Who Experienced UCR Within 2 Years From Randomization [Up to 2 years]

    The time (in days) from study start to the first occurrence of UCR was recorded. A CEC reviewed and adjudicated each suspected efficacy endpoint event while blinded to treatment. Participants who did not have any endpoint event until last visit or participants who were lost to follow-up and had no event were censored at the time of last available information (last study visit). If a participant had a fatal event that was not part of a specific endpoint for analysis, they were censored at the time of death. The Kaplan-Meier estimate reports the percentage of participants who experienced UCR within 2 years from randomization.

12. Kaplan-Meier Estimate of the Percentage of Participants Who Died From Any Cause Within 2 Years From Randomization [Up to 2 years]

    The time (in days) from study start to death from any cause was recorded. A CEC reviewed and adjudicated each suspected efficacy endpoint event while blinded to treatment. Participants who did not have any endpoint event until last visit or participants who were lost to follow-up and had no event were censored at the time of last available information (last study visit). The Kaplan-Meier estimate reports the percentage of participants who died from any cause within 2 years from randomization.

13. Kaplan-Meier Estimate of the Percentage of Participants Who Experienced a Stroke Within 2 Years From Randomization [Up to 2 years]

    The time (in days) from study start to first experience of a stroke was recorded. A CEC reviewed and adjudicated each suspected efficacy endpoint event while blinded to treatment. Participants who did not have any endpoint event until last visit or participants who were lost to follow-up and had no event were censored at the time of last available information (last study visit). If a participant had a fatal event that was not part of a specific endpoint for analysis, they were censored at the time of death. The Kaplan-Meier estimate reports the percentage of participants who experienced a stroke within 2 years from randomization.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

Men and women at least 18 years old with current clinical manifestation of non-ST-segment-elevation myocardial infarction (heart attack) according to the following three criteria:

• current symptoms of cardiac ischemia (chest pain leading to cardiac ischemia or heart attack)

AND

• either of the following:

• concurrent elevation of troponin I or T, or of creatine kinase - myocardial band (CK-MB) to a level above the upper limit of normal, OR

• concurrent appropriate electrocardiographic evidence

AND

• any one (or more) of the following:

• age >= 55 years

• documented history of prior heart attack or coronary revascularization (eg, angioplasty [PCI], coronary artery replacement [CABG])

• diabetes (documented use of insulin or oral hypoglycemic[s])

• documented history of peripheral arterial disease

Exclusion Criteria:

• history of intracranial hemorrhage or of central nervous system (CNS) surgery, tumor, or aneurysm

• any bleeding disorder or abnormality

• sustained severe hypertension or valvular heart disease

• current or recent platelet count <100,000 mm^3

• planned or ongoing treatment with a blood thinning medication

• pregnancy

• any significant medical or physiological condition or abnormality that could put the subject at increased risk or limit the subject's ability to participate for the duration of the study

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Merck Sharp & Dohme LLC
• Duke Clinical Research Institute

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Merck Sharp & Dohme LLC
• ClinicalTrials.gov Identifier: NCT00527943
• Other Study ID Numbers: P04736; TRA•CER; 2006-002809-31; MK-5348-014
• First Posted: Sep 11, 2007
• Last Update Posted: Sep 21, 2018
• Last Verified: Aug 1, 2018

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Additional relevant MeSH terms: Myocardial Infarction; Acute Coronary Syndrome; Atherosclerosis; Myocardial Ischemia; Infarction; Ischemia; Vorapaxar

Study Results

Participant Flow

Recruitment Details	Prior to the planned study completion, the Data Safety Monitoring Board recommended that all participants stop treatment and that the study be closed-out. The protocol-defined target number of primary efficacy endpoints had been reached by this time. However, follow-up in the study was terminated earlier than planned.
Pre-assignment Detail	The Intent to Treat (ITT) Population, defined as all enrolled participants who were randomly assigned to a treatment group.

Arm/Group Title	Placebo	Vorapaxar
Arm/Group Description	Loading oral dose of one 40 mg vorapaxar placebo tablet on Day 1, then one 2.5 mg vorapaxar placebo tablet daily, orally for at least 1 year in addition to current treatment of acute coronary syndrome, which will be continued to be administered as per current stand of care.	Loading oral dose of one 40 mg vorapaxar tablet on Day 1, then one 2.5 mg vorapaxar tablet daily, orally for at least 1 year in addition to current treatment of acute coronary syndrome, which will be continued to be administered as per current stand of care.
Period Title: Overall Study
STARTED	6471	6473
Received Treatment	6441	6446
COMPLETED	6311	6327
NOT COMPLETED	160	146

Baseline Characteristics

Arm/Group Title	Placebo	Vorapaxar	Total
Arm/Group Description	Loading oral dose of one 40 mg vorapaxar placebo tablet on Day 1, then one 2.5 mg vorapaxar placebo tablet daily, orally for at least 1 year in addition to current treatment of acute coronary syndrome, which will be continued to be administered as per current stand of care.	Loading oral dose of one 40 mg vorapaxar tablet on Day 1, then one 2.5 mg vorapaxar tablet daily, orally for at least 1 year in addition to current treatment of acute coronary syndrome, which will be continued to be administered as per current stand of care.	Total of all reporting groups
Overall Participants	6471	6473	12944
Age, Customized (Number) [Number]
<65 years	3369 52.1%	3390 52.4%	6759 52.2%
65 to <75 years	2006 31%	1973 30.5%	3979 30.7%
>= 75 years	1096 16.9%	1110 17.1%	2206 17%
Sex: Female, Male (Count of Participants)
Female	1822 28.2%	1810 28%	3632 28.1%
Male	4649 71.8%	4663 72%	9312 71.9%

Outcome Measures

1. Primary Outcome

Title	Kaplan-Meier Estimate of the Percentage of Participants Who Experienced Cardiovascular Death, Myocardial Infarction, Stroke, Recurrent Ischemia With Re-hospitalization, and/or Urgent Coronary Revascularization Within 2 Years From Randomization
Description	The time (in days) from study start to the first occurrence of any of the following clinical outcomes was recorded: cardiovascular (CV) death, myocardial infarction (MI), stroke, recurrent ischemia with re-hospitalization (RIR), and/or urgent coronary revascularization (UCR). A Clinical Endpoints Committee (CEC) reviewed and adjudicated each suspected efficacy endpoint event while blinded to treatment. Participants who did not have any endpoint event until last visit or participants who were lost to follow-up and had no event were censored at the time of last available information (last study visit). If a participant had a fatal event that was not part of a specific endpoint for analysis, they were censored at the time of death. The Kaplan-Meier estimate reports the percentage of participants who experienced at least 1 of the components of the primary composite efficacy endpoint within 2 years from randomization.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

Intent to Treat Population, defined as all participants who were randomly assigned to a treatment arm.

Arm/Group Title	Placebo	Vorapaxar
Arm/Group Description	Loading oral dose of one 40 mg vorapaxar placebo tablet on Day 1, then one 2.5 mg vorapaxar placebo tablet daily, orally for at least 1 year in addition to current treatment of acute coronary syndrome, which will be continued to be administered as per current stand of care.	Loading oral dose of one 40 mg vorapaxar tablet on Day 1, then one 2.5 mg vorapaxar tablet daily, orally for at least 1 year in addition to current treatment of acute coronary syndrome, which will be continued to be administered as per current stand of care.
Measure Participants	6471	6473
Number [Percentage of Participants]	19.9 0.3%	18.5 0.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Vorapaxar
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.072
	Comments
	Method	Cox Proportional Hazards Regression
	Comments	Hazard Ratio calculated with covariates for treatment and stratification factors
Method of Estimation	Estimation Parameter	Cox Proportional Hazard
	Estimated Value	0.92
	Confidence Interval	(2-Sided) 95%; 0.85 to 1.01
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard ratio calculated by dividing the Kaplan-Meier (KM) Estimate for vorapaxar by the KM Estimate for Placebo and correcting for covariates. A hazard ratio <1 would indicate a lower hazard associated with vorapaxar relative to placebo.

2. Secondary Outcome

Title	Kaplan-Meier Estimate of the Percentage of Participants Who Experienced Cardiovascular Death, Myocardial Infarction, and/or Stroke Within 2 Years From Randomization
Description	The time (in days) from study start to the first occurrence of any of the following clinical outcomes was recorded: cardiovascular (CV) death, myocardial infarction (MI), and/or stroke. A CEC reviewed and adjudicated each suspected efficacy endpoint event while blinded to treatment. Participants who did not have any endpoint event until last visit or participants who were lost to follow-up and had no event were censored at the time of last available information (last study visit). If a participant had a fatal event that was not part of a specific endpoint for analysis, they were censored at the time of death. The Kaplan-Meier estimate reports the percentage of participants who experienced at least 1 of the components of the secondary composite efficacy endpoint within 2 years from randomization.
Time Frame	up to 2 years

Outcome Measure Data

Analysis Population Description

Intent to Treat Population, defined as all participants who were randomly assigned to a treatment arm.

Arm/Group Title	Placebo	Vorapaxar
Arm/Group Description	Loading oral dose of one 40 mg vorapaxar placebo tablet on Day 1, then one 2.5 mg vorapaxar placebo tablet daily, orally for at least 1 year in addition to current treatment of acute coronary syndrome, which will be continued to be administered as per current stand of care.	Loading oral dose of one 40 mg vorapaxar tablet on Day 1, then one 2.5 mg vorapaxar tablet daily, orally for at least 1 year in addition to current treatment of acute coronary syndrome, which will be continued to be administered as per current stand of care.
Measure Participants	6471	6473
Number [Percentage of Participants]	16.4 0.3%	14.7 0.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Vorapaxar
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.018
	Comments
	Method	Cox Proportional Hazards Regression
	Comments	Hazard Ratio calculated with covariates for treatment and stratification factors
Method of Estimation	Estimation Parameter	Cox Proportional Hazard
	Estimated Value	0.89
	Confidence Interval	(2-Sided) 95%; 0.81 to 0.98
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard ratio calculated by dividing the Kaplan-Meier (KM) Estimate for vorapaxar by the KM Estimate for Placebo and correcting for covariates. A hazard ratio <1 would indicate a lower hazard associated with vorapaxar relative to placebo.

3. Secondary Outcome

Title	Kaplan-Meier Estimate of the Percentage of Participants Who Met Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Arteries (GUSTO) Moderate or Severe Bleeding Criteria Within 2 Years From Randomization
Description	Adverse events were categorized as "bleeding events" if the intensity of the event was other or more than would be normally expected in the given situation (eg, mild nosebleed in a person who does not normally have nosebleeds, greater bruising than expected for a given injury, greater volume of blood loss than expected for a given procedure). The investigator graded the intensity of bleeding events according to the GUSTO cooperative group criteria as follows: Mild , Moderate or Severe and the grading was adjudicated by the CEC. The Kaplan-Meier estimate reports the percentage of participants who experienced GUSTO moderate or severe bleeding within 2 years from randomization.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

As Treated Population, which included all participants who received at least 1 dose of study medication.

Arm/Group Title	Placebo	Vorapaxar
Arm/Group Description	Loading oral dose of one 40 mg vorapaxar placebo tablet on Day 1, then one 2.5 mg vorapaxar placebo tablet daily, orally for at least 1 year in addition to current treatment of acute coronary syndrome, which will be continued to be administered as per current stand of care.	Loading oral dose of one 40 mg vorapaxar tablet on Day 1, then one 2.5 mg vorapaxar tablet daily, orally for at least 1 year in addition to current treatment of acute coronary syndrome, which will be continued to be administered as per current stand of care.
Measure Participants	6441	6446
Number [Percentage of Participants]	5.8 0.1%	7.6 0.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Vorapaxar
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Cox Proportional Hazards Regression
	Comments	Hazard Ratio calculated with covariates for treatment and stratification factors
Method of Estimation	Estimation Parameter	Cox Proportional Hazard
	Estimated Value	1.36
	Confidence Interval	(2-Sided) 95%; 1.18 to 1.57
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard ratio calculated by dividing the Kaplan-Meier (KM) Estimate for vorapaxar by the KM Estimate for Placebo and correcting for covariates. A hazard ratio <1 would indicate a lower hazard associated with vorapaxar relative to placebo.

4. Secondary Outcome

Title	Kaplan-Meier Estimate of the Percentage of Participants Who Experienced Clinically Significant Bleeding Within 2 Years From Randomization
Description	Adverse events were categorized as "bleeding events" if the intensity of the event was other or more than would be normally expected in the given situation (eg, mild nosebleed in a person who does not normally have nosebleeds, greater bruising than expected for a given injury, greater volume of blood loss than expected for a given procedure). The investigator graded the intensity of bleeding events according to the Thrombolysis in Myocardial Infarction (TIMI) Study Group criteria as major, minor or other. "Clinically Significant Bleeding" was defined as the composite of TIMI Major bleeding, TIMI Minor bleeding, or bleeding that required unplanned medical or surgical treatment or unplanned laboratory evaluation even if it did not meet the criteria for TIMI major or minor bleeding. The Kaplan-Meier estimate reports the percentage of participants who experienced clinically significant bleeding within 2 years from randomization.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

As Treated Population, which included all participants who received at least 1 dose of study medication.

Arm/Group Title	Placebo	Vorapaxar
Arm/Group Description	Loading oral dose of one 40 mg vorapaxar placebo tablet on Day 1, then one 2.5 mg vorapaxar placebo tablet daily, orally for at least 1 year in addition to current treatment of acute coronary syndrome, which will be continued to be administered as per current stand of care.	Loading oral dose of one 40 mg vorapaxar tablet on Day 1, then one 2.5 mg vorapaxar tablet daily, orally for at least 1 year in addition to current treatment of acute coronary syndrome, which will be continued to be administered as per current stand of care.
Measure Participants	6441	6446
Number [Percentage of Participants]	14.6 0.2%	19.5 0.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Vorapaxar
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Cox Proportional Hazards Regression
	Comments	Hazard Ratio calculated with covariates for treatment and stratification factors
Method of Estimation	Estimation Parameter	Cox Proportional Hazard
	Estimated Value	1.41
	Confidence Interval	(2-Sided) 95%; 1.29 to 1.54
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard ratio calculated by dividing the Kaplan-Meier (KM) Estimate for vorapaxar by the KM Estimate for Placebo and correcting for covariates. A hazard ratio <1 would indicate a lower hazard associated with vorapaxar relative to placebo.

5. Secondary Outcome

Title	Kaplan-Meier Estimate of the Percentage of Participants Who Experienced CV Death, MI, Stroke, or UCR Within 2 Years From Randomization
Description	The time (in days) from study start to the first occurrence of any of the following clinical outcomes was recorded: CV death, MI, stroke, or UCR. A CEC reviewed and adjudicated each suspected efficacy endpoint event while blinded to treatment. Participants who did not have any endpoint event until last visit or participants who were lost to follow-up and had no event were censored at the time of last available information (last study visit). If a participant had a fatal event that was not part of a specific endpoint for analysis, they were censored at the time of death. The Kaplan-Meier estimate reports the percentage of participants who experienced CV death, MI, stroke, or UCR within 2 years from randomization.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

Intent to Treat Population, defined as all participants who were randomly assigned to a treatment arm.

Arm/Group Title	Placebo	Vorapaxar
Arm/Group Description	Loading oral dose of one 40 mg vorapaxar placebo tablet on Day 1, then one 2.5 mg vorapaxar placebo tablet daily, orally for at least 1 year in addition to current treatment of acute coronary syndrome, which will be continued to be administered as per current stand of care.	Loading oral dose of one 40 mg vorapaxar tablet on Day 1, then one 2.5 mg vorapaxar tablet daily, orally for at least 1 year in addition to current treatment of acute coronary syndrome, which will be continued to be administered as per current stand of care.
Measure Participants	6471	6473
Number [Percentage of Participants]	19.2 0.3%	17.5 0.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Vorapaxar
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.038
	Comments
	Method	Cox Proportional Hazards Regression
	Comments	Hazard Ratio calculated with covariates for treatment and stratification factors
Method of Estimation	Estimation Parameter	Cox Proportional Hazard
	Estimated Value	0.91
	Confidence Interval	(2-Sided) 95%; 0.84 to 1.00
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard ratio calculated by dividing the Kaplan-Meier (KM) Estimate for vorapaxar by the KM Estimate for Placebo and correcting for covariates. A hazard ratio <1 would indicate a lower hazard associated with vorapaxar relative to placebo.

6. Secondary Outcome

Title	Kaplan-Meier Estimate of the Percentage of Participants Who Experienced CV Death or MI Within 2 Years From Randomization
Description	The time (in days) from study start to the first occurrence of any of the following clinical outcomes was recorded: CV death or MI. A CEC reviewed and adjudicated each suspected efficacy endpoint event while blinded to treatment. Participants who did not have any endpoint event until last visit or participants who were lost to follow-up and had no event were censored at the time of last available information (last study visit). If a participant had a fatal event that was not part of a specific endpoint for analysis, they were censored at the time of death. The Kaplan-Meier estimate reports the percentage of participants who experienced CV death or MI within 2 years from randomization.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

Intent to Treat Population, defined as all participants who were randomly assigned to a treatment arm.

Arm/Group Title	Placebo	Vorapaxar
Arm/Group Description	Loading oral dose of one 40 mg vorapaxar placebo tablet on Day 1, then one 2.5 mg vorapaxar placebo tablet daily, orally for at least 1 year in addition to current treatment of acute coronary syndrome, which will be continued to be administered as per current stand of care.	Loading oral dose of one 40 mg vorapaxar tablet on Day 1, then one 2.5 mg vorapaxar tablet daily, orally for at least 1 year in addition to current treatment of acute coronary syndrome, which will be continued to be administered as per current stand of care.
Measure Participants	6471	6473
Number [Percentage of Participants]	14.9 0.2%	13.5 0.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Vorapaxar
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.027
	Comments
	Method	Cox Proportional Hazards Regression
	Comments	Hazard Ratio calculated with covariates for treatment and stratification factors
Method of Estimation	Estimation Parameter	Cox Proportional Hazard
	Estimated Value	0.90
	Confidence Interval	(2-Sided) 95%; 0.81 to 0.99
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard ratio calculated by dividing the Kaplan-Meier (KM) Estimate for vorapaxar by the KM Estimate for Placebo and correcting for covariates. A hazard ratio <1 would indicate a lower hazard associated with vorapaxar relative to placebo.

7. Secondary Outcome

Title	Kaplan-Meier Estimate of the Percentage of Participants Who Experienced All-cause Death, MI, Stroke, RIR, or UCR Within 2 Years From Randomization
Description	The time (in days) from study start to the first occurrence of any of the following clinical outcomes was recorded: all-cause death, MI, stroke, RIR, or UCR. A CEC reviewed and adjudicated each suspected efficacy endpoint event while blinded to treatment. Participants who did not have any endpoint event until last visit or participants who were lost to follow-up and had no event were censored at the time of last available information (last study visit). The Kaplan-Meier estimate reports the percentage of participants who experienced all-cause death, MI, stroke, RIR, or UCR within 2 years from randomization.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

Intent to Treat population, defined as all participants who were randomly assigned to a treatment arm.

Arm/Group Title	Placebo	Vorapaxar
Arm/Group Description	Loading oral dose of one 40 mg vorapaxar placebo tablet on Day 1, then one 2.5 mg vorapaxar placebo tablet daily, orally for at least 1 year in addition to current treatment of acute coronary syndrome, which will be continued to be administered as per current stand of care.	Loading oral dose of one 40 mg vorapaxar tablet on Day 1, then one 2.5 mg vorapaxar tablet daily, orally for at least 1 year in addition to current treatment of acute coronary syndrome, which will be continued to be administered as per current stand of care.
Measure Participants	6471	6473
Number [Percentage of Participants]	21.5 0.3%	20.6 0.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Vorapaxar
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.174
	Comments
	Method	Cox Proportional Hazards Regression
	Comments	Hazard Ratio calculated with covariates for treatment and stratification factors
Method of Estimation	Estimation Parameter	Cox Proportional Hazard
	Estimated Value	0.94
	Confidence Interval	(2-Sided) 95%; 0.87 to 1.03
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard ratio calculated by dividing the Kaplan-Meier (KM) Estimate for vorapaxar by the KM Estimate for Placebo and correcting for covariates. A hazard ratio <1 would indicate a lower hazard associated with vorapaxar relative to placebo.

8. Secondary Outcome

Title	Kaplan-Meier Estimate of the Percentage of Participants Who Experienced All-cause Death, MI, Stroke, or UCR Within 2 Years From Randomization
Description	The time (in days) from study start to the first occurrence of any of the following clinical outcomes was recorded: all-cause death, MI, stroke, or UCR. A CEC reviewed and adjudicated each suspected efficacy endpoint event while blinded to treatment. Participants who did not have any endpoint event until last visit or participants who were lost to follow-up and had no event were censored at the time of last available information (last study visit). The Kaplan-Meier estimate reports the percentage of participants who experienced all-cause Death, MI, stroke, or UCR I within 2 years from randomization.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

Intent to Treat Population, defined as all participants who were randomly assigned to a treatment arm.

Arm/Group Title	Placebo	Vorapaxar
Arm/Group Description	Loading oral dose of one 40 mg vorapaxar placebo tablet on Day 1, then one 2.5 mg vorapaxar placebo tablet daily, orally for at least 1 year in addition to current treatment of acute coronary syndrome, which will be continued to be administered as per current stand of care.	Loading oral dose of one 40 mg vorapaxar tablet on Day 1, then one 2.5 mg vorapaxar tablet daily, orally for at least 1 year in addition to current treatment of acute coronary syndrome, which will be continued to be administered as per current stand of care.
Measure Participants	6471	6473
Number [Percentage of Participants]	20.8 0.3%	19.6 0.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Vorapaxar
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.108
	Comments
	Method	Cox Proportional Hazards Regression
	Comments	Hazard Ratio calculated with covariates for treatment and stratification factors
Method of Estimation	Estimation Parameter	Cox Proportional Hazard
	Estimated Value	0.93
	Confidence Interval	(2-Sided) 95%; 0.86 to 1.02
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard ratio calculated by dividing the Kaplan-Meier (KM) Estimate for vorapaxar by the KM Estimate for Placebo and correcting for covariates. A hazard ratio <1 would indicate a lower hazard associated with vorapaxar relative to placebo.

9. Secondary Outcome

Title	Kaplan-Meier Estimate of the Percentage of Participants Who Experienced CV Death Within 2 Years From Randomization
Description	The time (in days) from study start to the CV death (if reported) was recorded. A CEC reviewed and adjudicated each suspected efficacy endpoint event while blinded to treatment. Participants who did not have any endpoint event until last visit or participants who were lost to follow-up and had no event were censored at the time of last available information (last study visit). If a participant had a fatal event that was not part of a specific endpoint for analysis, they were censored at the time of death. The Kaplan-Meier estimate reports the percentage of participants who experienced CV death within 2 years from randomization.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

Intent to Treat Population, defined as all participants who were randomly assigned to a treatment arm.

Arm/Group Title	Placebo	Vorapaxar
Arm/Group Description	Loading oral dose of one 40 mg vorapaxar placebo tablet on Day 1, then one 2.5 mg vorapaxar placebo tablet daily, orally for at least 1 year in addition to current treatment of acute coronary syndrome, which will be continued to be administered as per current stand of care.	Loading oral dose of one 40 mg vorapaxar tablet on Day 1, then one 2.5 mg vorapaxar tablet daily, orally for at least 1 year in addition to current treatment of acute coronary syndrome, which will be continued to be administered as per current stand of care.
Measure Participants	6471	6473
Number [Percentage of Participants]	3.8 0.1%	3.8 0.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Vorapaxar
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.963
	Comments
	Method	Cox Proportional Hazards Regression
	Comments	Hazard Ratio calculated with covariates for treatment and stratification factors
Method of Estimation	Estimation Parameter	Cox Proportional Hazard
	Estimated Value	1.00
	Confidence Interval	(2-Sided) 95%; 0.83 to 1.22
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard ratio calculated by dividing the Kaplan-Meier (KM) Estimate for vorapaxar by the KM Estimate for Placebo and correcting for covariates. A hazard ratio <1 would indicate a lower hazard associated with vorapaxar relative to placebo.

10. Secondary Outcome

Title	Kaplan-Meier Estimate of the Percentage of Participants Who Experienced an MI Within 2 Years From Randomization
Description	The time (in days) from study start to the first occurrence of an MI was recorded. A CEC reviewed and adjudicated each suspected efficacy endpoint event while blinded to treatment. Participants who did not have any endpoint event until last visit or participants who were lost to follow-up and had no event were censored at the time of last available information (last study visit). If a participant had a fatal event that was not part of a specific endpoint for analysis, they were censored at the time of death. The Kaplan-Meier estimate reports the percentage of participants who experienced an MI within 2 years from randomization.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

Intent to Treat Population, defined as all participants who were randomly assigned to a treatment arm.

Arm/Group Title	Placebo	Vorapaxar
Arm/Group Description	Loading oral dose of one 40 mg vorapaxar placebo tablet on Day 1, then one 2.5 mg vorapaxar placebo tablet daily, orally for at least 1 year in addition to current treatment of acute coronary syndrome, which will be continued to be administered as per current stand of care.	Loading oral dose of one 40 mg vorapaxar tablet on Day 1, then one 2.5 mg vorapaxar tablet daily, orally for at least 1 year in addition to current treatment of acute coronary syndrome, which will be continued to be administered as per current stand of care.
Measure Participants	6471	6473
Number [Percentage of Participants]	12.5 0.2%	11.1 0.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Vorapaxar
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.021
	Comments
	Method	Cox Proportional Hazards Regression
	Comments	Hazard Ratio calculated with covariates for treatment and stratification factors
Method of Estimation	Estimation Parameter	Cox Proportional Hazard
	Estimated Value	0.88
	Confidence Interval	(2-Sided) 95%; 0.79 to 0.98
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard ratio calculated by dividing the Kaplan-Meier (KM) Estimate for vorapaxar by the KM Estimate for Placebo and correcting for covariates. A hazard ratio <1 would indicate a lower hazard associated with vorapaxar relative to placebo.

11. Secondary Outcome

Title	Kaplan-Meier Estimate of the Percentage of Participants Who Experienced RIR Within 2 Years From Randomization
Description	The time (in days) from study start to the first occurrence of RIR was recorded. A CEC reviewed and adjudicated each suspected efficacy endpoint event while blinded to treatment. Participants who did not have any endpoint event until last visit or participants who were lost to follow-up and had no event were censored at the time of last available information (last study visit). If a participant had a fatal event that was not part of a specific endpoint for analysis, they were censored at the time of death. The Kaplan-Meier estimate reports the percentage of participants who experienced RIR within 2 years from randomization.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

Intent to Treat Population, defined as all participants who were randomly assigned to a treatment arm

Arm/Group Title	Placebo	Vorapaxar
Arm/Group Description	Loading oral dose of one 40 mg vorapaxar placebo tablet on Day 1, then one 2.5 mg vorapaxar placebo tablet daily, orally for at least 1 year in addition to current treatment of acute coronary syndrome, which will be continued to be administered as per current stand of care.	Loading oral dose of one 40 mg vorapaxar tablet on Day 1, then one 2.5 mg vorapaxar tablet daily, orally for at least 1 year in addition to current treatment of acute coronary syndrome, which will be continued to be administered as per current stand of care.
Measure Participants	6471	6473
Number [Percentage of Participants]	1.5 0%	1.6 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Vorapaxar
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.418
	Comments
	Method	Cox Proportional Hazards Regression
	Comments	Hazard Ratio calculated with covariates for treatment and stratification factors
Method of Estimation	Estimation Parameter	Cox Proportional Hazard
	Estimated Value	1.14
	Confidence Interval	(2-Sided) 95%; 0.83 to 1.58
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard ratio calculated by dividing the Kaplan-Meier (KM) Estimate for vorapaxar by the KM Estimate for Placebo and correcting for covariates. A hazard ratio <1 would indicate a lower hazard associated with vorapaxar relative to placebo.

12. Secondary Outcome

Title	Kaplan-Meier Estimate of the Percentage of Participants Who Experienced UCR Within 2 Years From Randomization
Description	The time (in days) from study start to the first occurrence of UCR was recorded. A CEC reviewed and adjudicated each suspected efficacy endpoint event while blinded to treatment. Participants who did not have any endpoint event until last visit or participants who were lost to follow-up and had no event were censored at the time of last available information (last study visit). If a participant had a fatal event that was not part of a specific endpoint for analysis, they were censored at the time of death. The Kaplan-Meier estimate reports the percentage of participants who experienced UCR within 2 years from randomization.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

Intent to Treat Population, defined as all participants who were randomly assigned to a treatment arm.

Arm/Group Title	Placebo	Vorapaxar
Arm/Group Description	Loading oral dose of one 40 mg vorapaxar placebo tablet on Day 1, then one 2.5 mg vorapaxar placebo tablet daily, orally for at least 1 year in addition to current treatment of acute coronary syndrome, which will be continued to be administered as per current stand of care.	Loading oral dose of one 40 mg vorapaxar tablet on Day 1, then one 2.5 mg vorapaxar tablet daily, orally for at least 1 year in addition to current treatment of acute coronary syndrome, which will be continued to be administered as per current stand of care.
Measure Participants	6471	6473
Number [Percentage of Participants]	3.5 0.1%	3.8 0.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Vorapaxar
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.493
	Comments
	Method	Cox Proportional Hazards Regression
	Comments	Hazard Ratio calculated with covariates for treatment and stratification factors
Method of Estimation	Estimation Parameter	Cox Proportional Hazard
	Estimated Value	1.07
	Confidence Interval	(2-Sided) 95%; 0.88 to 1.31
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard ratio calculated by dividing the Kaplan-Meier (KM) Estimate for vorapaxar by the KM Estimate for Placebo and correcting for covariates. A hazard ratio <1 would indicate a lower hazard associated with vorapaxar relative to placebo.

13. Secondary Outcome

Title	Kaplan-Meier Estimate of the Percentage of Participants Who Died From Any Cause Within 2 Years From Randomization
Description	The time (in days) from study start to death from any cause was recorded. A CEC reviewed and adjudicated each suspected efficacy endpoint event while blinded to treatment. Participants who did not have any endpoint event until last visit or participants who were lost to follow-up and had no event were censored at the time of last available information (last study visit). The Kaplan-Meier estimate reports the percentage of participants who died from any cause within 2 years from randomization.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

Intent to Treat Population, defined as all participants who were randomly assigned to a treatment arm.

Arm/Group Title	Placebo	Vorapaxar
Arm/Group Description	Loading oral dose of one 40 mg vorapaxar placebo tablet on Day 1, then one 2.5 mg vorapaxar placebo tablet daily, orally for at least 1 year in addition to current treatment of acute coronary syndrome, which will be continued to be administered as per current stand of care.	Loading oral dose of one 40 mg vorapaxar tablet on Day 1, then one 2.5 mg vorapaxar tablet daily, orally for at least 1 year in addition to current treatment of acute coronary syndrome, which will be continued to be administered as per current stand of care.
Measure Participants	6471	6473
Number [Percentage of Participants]	6.1 0.1%	6.5 0.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Vorapaxar
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.515
	Comments
	Method	Cox Proportional Hazards Regression
	Comments	Hazard Ratio calculated with covariates for treatment and stratification factors
Method of Estimation	Estimation Parameter	Cox Proportional Hazard
	Estimated Value	1.05
	Confidence Interval	(2-Sided) 95%; 0.90 to 1.23
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard ratio calculated by dividing the Kaplan-Meier (KM) Estimate for vorapaxar by the KM Estimate for Placebo and correcting for covariates. A hazard ratio <1 would indicate a lower hazard associated with vorapaxar relative to placebo.

14. Secondary Outcome

Title	Kaplan-Meier Estimate of the Percentage of Participants Who Experienced a Stroke Within 2 Years From Randomization
Description	The time (in days) from study start to first experience of a stroke was recorded. A CEC reviewed and adjudicated each suspected efficacy endpoint event while blinded to treatment. Participants who did not have any endpoint event until last visit or participants who were lost to follow-up and had no event were censored at the time of last available information (last study visit). If a participant had a fatal event that was not part of a specific endpoint for analysis, they were censored at the time of death. The Kaplan-Meier estimate reports the percentage of participants who experienced a stroke within 2 years from randomization.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

Intent to Treat Population, defined as all participants who were randomly assigned to a treatment arm.

Arm/Group Title	Placebo	Vorapaxar
Arm/Group Description	Loading oral dose of one 40 mg vorapaxar placebo tablet on Day 1, then one 2.5 mg vorapaxar placebo tablet daily, orally for at least 1 year in addition to current treatment of acute coronary syndrome, which will be continued to be administered as per current stand of care.	Loading oral dose of one 40 mg vorapaxar tablet on Day 1, then one 2.5 mg vorapaxar tablet daily, orally for at least 1 year in addition to current treatment of acute coronary syndrome, which will be continued to be administered as per current stand of care.
Measure Participants	6471	6473
Number [Percentage of Participants]	2.1 0%	1.9 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Vorapaxar
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.606
	Comments
	Method	Cox Proportional Hazards Regression
	Comments	Hazard Ratio calculated with covariates for treatment and stratification factors
Method of Estimation	Estimation Parameter	Cox Proportional Hazard
	Estimated Value	0.93
	Confidence Interval	(2-Sided) 95%; 0.70 to 1.23
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard ratio calculated by dividing the Kaplan-Meier (KM) Estimate for vorapaxar by the KM Estimate for Placebo and correcting for covariates. A hazard ratio <1 would indicate a lower hazard associated with vorapaxar relative to placebo.

Adverse Events

Adverse Event Reporting Description	Adverse events are reported using the As Treated Population, which included all participants who received at least 1 dose of study medication and are reported according to treatment received.
Arm/Group Title	Placebo		Vorapaxar
Arm/Group Description	Loading oral dose of one 40 mg vorapaxar placebo tablet on Day 1, then one 2.5 mg vorapaxar placebo tablet daily, orally for at least 1 year in addition to current treatment of acute coronary syndrome, which will be continued to be administered as per current stand of care.		Loading oral dose of one 40 mg vorapaxar tablet on Day 1, then one 2.5 mg vorapaxar tablet daily, orally for at least 1 year in addition to current treatment of acute coronary syndrome, which will be continued to be administered as per current stand of care.
All Cause Mortality
	Placebo		Vorapaxar
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Vorapaxar
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1718/6441 (26.7%)		1866/6446 (28.9%)
Blood and lymphatic system disorders
ANAEMIA	28/6441 (0.4%)	29	55/6446 (0.9%)	59
COAGULOPATHY	2/6441 (0%)	2	3/6446 (0%)	3
DISSEMINATED INTRAVASCULAR COAGULATION	1/6441 (0%)	1	0/6446 (0%)	0
EOSINOPHILIA	1/6441 (0%)	1	0/6446 (0%)	0
FEBRILE NEUTROPENIA	0/6441 (0%)	0	1/6446 (0%)	1
GRANULOCYTOPENIA	1/6441 (0%)	2	0/6446 (0%)	0
HAEMORRHAGIC ANAEMIA	1/6441 (0%)	1	3/6446 (0%)	3
HAEMORRHAGIC DIATHESIS	1/6441 (0%)	1	10/6446 (0.2%)	10
HEPARIN-INDUCED THROMBOCYTOPENIA	3/6441 (0%)	3	1/6446 (0%)	1
HYPOCHROMIC ANAEMIA	0/6441 (0%)	0	2/6446 (0%)	3
IDIOPATHIC THROMBOCYTOPENIC PURPURA	1/6441 (0%)	1	0/6446 (0%)	0
IRON DEFICIENCY ANAEMIA	1/6441 (0%)	1	8/6446 (0.1%)	8
LEUKOCYTOSIS	1/6441 (0%)	1	1/6446 (0%)	1
LYMPHADENOPATHY	2/6441 (0%)	2	1/6446 (0%)	1
LYMPHADENOPATHY MEDIASTINAL	2/6441 (0%)	2	0/6446 (0%)	0
MICROCYTIC ANAEMIA	3/6441 (0%)	3	2/6446 (0%)	2
NORMOCHROMIC NORMOCYTIC ANAEMIA	0/6441 (0%)	0	1/6446 (0%)	1
SPLENIC INFARCTION	1/6441 (0%)	1	0/6446 (0%)	0
SPONTANEOUS HAEMATOMA	1/6441 (0%)	1	0/6446 (0%)	0
THROMBOCYTOPENIA	34/6441 (0.5%)	34	30/6446 (0.5%)	30
THROMBOCYTOSIS	2/6441 (0%)	2	2/6446 (0%)	2
Cardiac disorders
ANGINA PECTORIS	3/6441 (0%)	3	6/6446 (0.1%)	6
ANGINA UNSTABLE	0/6441 (0%)	0	2/6446 (0%)	2
AORTIC VALVE DISEASE	1/6441 (0%)	1	0/6446 (0%)	0
AORTIC VALVE INCOMPETENCE	0/6441 (0%)	0	3/6446 (0%)	3
AORTIC VALVE STENOSIS	1/6441 (0%)	1	2/6446 (0%)	2
ARRHYTHMIA	5/6441 (0.1%)	5	6/6446 (0.1%)	6
ARRHYTHMIA SUPRAVENTRICULAR	1/6441 (0%)	1	3/6446 (0%)	5
ARTERIOSCLEROSIS CORONARY ARTERY	0/6441 (0%)	0	1/6446 (0%)	1
ARTERIOSPASM CORONARY	1/6441 (0%)	1	0/6446 (0%)	0
ATRIAL FIBRILLATION	93/6441 (1.4%)	100	96/6446 (1.5%)	113
ATRIAL FLUTTER	17/6441 (0.3%)	17	17/6446 (0.3%)	18
ATRIAL RUPTURE	1/6441 (0%)	1	0/6446 (0%)	0
ATRIAL THROMBOSIS	3/6441 (0%)	3	0/6446 (0%)	0
ATRIOVENTRICULAR BLOCK	1/6441 (0%)	1	4/6446 (0.1%)	4
ATRIOVENTRICULAR BLOCK COMPLETE	9/6441 (0.1%)	9	9/6446 (0.1%)	9
ATRIOVENTRICULAR BLOCK SECOND DEGREE	6/6441 (0.1%)	6	7/6446 (0.1%)	7
ATRIOVENTRICULAR DISSOCIATION	1/6441 (0%)	1	0/6446 (0%)	0
BIFASCICULAR BLOCK	1/6441 (0%)	1	0/6446 (0%)	0
BRADYARRHYTHMIA	0/6441 (0%)	0	1/6446 (0%)	1
BRADYCARDIA	26/6441 (0.4%)	26	14/6446 (0.2%)	14
BUNDLE BRANCH BLOCK LEFT	1/6441 (0%)	1	0/6446 (0%)	0
CARDIAC ARREST	12/6441 (0.2%)	12	9/6446 (0.1%)	9
CARDIAC ASTHMA	2/6441 (0%)	2	0/6446 (0%)	0
CARDIAC FAILURE	146/6441 (2.3%)	191	142/6446 (2.2%)	191
CARDIAC FAILURE ACUTE	1/6441 (0%)	1	1/6446 (0%)	1
CARDIAC FAILURE CHRONIC	4/6441 (0.1%)	5	1/6446 (0%)	1
CARDIAC FAILURE CONGESTIVE	35/6441 (0.5%)	46	45/6446 (0.7%)	53
CARDIAC HYPERTROPHY	1/6441 (0%)	1	0/6446 (0%)	0
CARDIAC PERFORATION	1/6441 (0%)	1	0/6446 (0%)	0
CARDIAC TAMPONADE	5/6441 (0.1%)	5	4/6446 (0.1%)	4
CARDIAC VALVE DISEASE	1/6441 (0%)	1	0/6446 (0%)	0
CARDIO-RESPIRATORY ARREST	3/6441 (0%)	3	2/6446 (0%)	2
CARDIOGENIC SHOCK	39/6441 (0.6%)	41	24/6446 (0.4%)	24
CARDIOMEGALY	0/6441 (0%)	0	1/6446 (0%)	1
CARDIOMYOPATHY	4/6441 (0.1%)	4	1/6446 (0%)	1
CARDIOPULMONARY FAILURE	3/6441 (0%)	3	3/6446 (0%)	3
CARDIOVASCULAR INSUFFICIENCY	0/6441 (0%)	0	1/6446 (0%)	1
CHORDAE TENDINAE RUPTURE	0/6441 (0%)	0	1/6446 (0%)	1
CONGESTIVE CARDIOMYOPATHY	1/6441 (0%)	1	0/6446 (0%)	0
COR PULMONALE	0/6441 (0%)	0	1/6446 (0%)	1
CORONARY ARTERY DISEASE	6/6441 (0.1%)	6	5/6446 (0.1%)	5
CORONARY ARTERY DISSECTION	1/6441 (0%)	1	1/6446 (0%)	1
CORONARY ARTERY INSUFFICIENCY	0/6441 (0%)	0	1/6446 (0%)	1
CORONARY ARTERY OCCLUSION	0/6441 (0%)	0	1/6446 (0%)	1
DRESSLER'S SYNDROME	1/6441 (0%)	1	2/6446 (0%)	2
EXTRASYSTOLES	1/6441 (0%)	1	1/6446 (0%)	1
GASTROCARDIAC SYNDROME	0/6441 (0%)	0	1/6446 (0%)	1
HEART VALVE CALCIFICATION	1/6441 (0%)	1	0/6446 (0%)	0
INTRACARDIAC THROMBUS	4/6441 (0.1%)	4	2/6446 (0%)	2
ISCHAEMIC CARDIOMYOPATHY	4/6441 (0.1%)	4	2/6446 (0%)	2
LEFT VENTRICULAR DYSFUNCTION	1/6441 (0%)	1	3/6446 (0%)	3
LEFT VENTRICULAR FAILURE	0/6441 (0%)	0	2/6446 (0%)	3
MITRAL VALVE INCOMPETENCE	6/6441 (0.1%)	6	5/6446 (0.1%)	5
MYOCARDIAL RUPTURE	1/6441 (0%)	1	1/6446 (0%)	1
MYOCARDITIS	1/6441 (0%)	1	0/6446 (0%)	0
MYOPERICARDITIS	1/6441 (0%)	1	0/6446 (0%)	0
NODAL ARRHYTHMIA	2/6441 (0%)	2	1/6446 (0%)	1
NODAL RHYTHM	2/6441 (0%)	2	0/6446 (0%)	0
PALPITATIONS	6/6441 (0.1%)	6	8/6446 (0.1%)	8
PAPILLARY MUSCLE RUPTURE	1/6441 (0%)	1	0/6446 (0%)	0
PERICARDIAL EFFUSION	7/6441 (0.1%)	7	7/6446 (0.1%)	7
PERICARDIAL HAEMORRHAGE	8/6441 (0.1%)	8	18/6446 (0.3%)	19
PERICARDITIS	5/6441 (0.1%)	5	3/6446 (0%)	3
PERICARDITIS CONSTRICTIVE	1/6441 (0%)	1	0/6446 (0%)	0
PLEUROPERICARDITIS	1/6441 (0%)	1	0/6446 (0%)	0
PRINZMETAL ANGINA	0/6441 (0%)	0	1/6446 (0%)	1
PULSELESS ELECTRICAL ACTIVITY	2/6441 (0%)	2	2/6446 (0%)	2
RESTRICTIVE CARDIOMYOPATHY	0/6441 (0%)	0	1/6446 (0%)	2
RIGHT VENTRICULAR DYSFUNCTION	1/6441 (0%)	1	0/6446 (0%)	0
RIGHT VENTRICULAR FAILURE	3/6441 (0%)	3	0/6446 (0%)	0
SICK SINUS SYNDROME	8/6441 (0.1%)	8	7/6446 (0.1%)	8
SINOATRIAL BLOCK	1/6441 (0%)	1	1/6446 (0%)	1
SINUS ARREST	0/6441 (0%)	0	1/6446 (0%)	1
SINUS ARRHYTHMIA	1/6441 (0%)	1	1/6446 (0%)	1
SINUS BRADYCARDIA	3/6441 (0%)	3	3/6446 (0%)	3
SINUS TACHYCARDIA	0/6441 (0%)	0	2/6446 (0%)	2
STRESS CARDIOMYOPATHY	1/6441 (0%)	1	1/6446 (0%)	1
SUPRAVENTRICULAR TACHYARRHYTHMIA	1/6441 (0%)	1	0/6446 (0%)	0
SUPRAVENTRICULAR TACHYCARDIA	15/6441 (0.2%)	15	9/6446 (0.1%)	11
TACHYCARDIA	2/6441 (0%)	2	2/6446 (0%)	3
TORSADE DE POINTES	1/6441 (0%)	1	1/6446 (0%)	1
TRICUSPID VALVE INCOMPETENCE	1/6441 (0%)	1	0/6446 (0%)	0
TRIFASCICULAR BLOCK	1/6441 (0%)	1	0/6446 (0%)	0
VENTRICLE RUPTURE	0/6441 (0%)	0	1/6446 (0%)	1
VENTRICULAR ARRHYTHMIA	1/6441 (0%)	1	3/6446 (0%)	3
VENTRICULAR DYSFUNCTION	1/6441 (0%)	1	0/6446 (0%)	0
VENTRICULAR EXTRASYSTOLES	1/6441 (0%)	1	4/6446 (0.1%)	4
VENTRICULAR FIBRILLATION	28/6441 (0.4%)	33	30/6446 (0.5%)	32
VENTRICULAR TACHYARRHYTHMIA	1/6441 (0%)	1	0/6446 (0%)	0
VENTRICULAR TACHYCARDIA	36/6441 (0.6%)	41	23/6446 (0.4%)	29
Congenital, familial and genetic disorders
ARTERIOVENOUS MALFORMATION	0/6441 (0%)	0	1/6446 (0%)	1
ATRIAL SEPTAL DEFECT	1/6441 (0%)	1	0/6446 (0%)	0
GASTROINTESTINAL ANGIODYSPLASIA	1/6441 (0%)	1	2/6446 (0%)	2
GASTROINTESTINAL ANGIODYSPLASIA HAEMORRHAGIC	0/6441 (0%)	0	1/6446 (0%)	1
GASTROINTESTINAL ARTERIOVENOUS MALFORMATION	0/6441 (0%)	0	1/6446 (0%)	1
HYDROCELE	1/6441 (0%)	1	1/6446 (0%)	1
PHIMOSIS	0/6441 (0%)	0	1/6446 (0%)	1
Ear and labyrinth disorders
DEAFNESS	1/6441 (0%)	1	0/6446 (0%)	0
DEAFNESS NEUROSENSORY	1/6441 (0%)	1	0/6446 (0%)	0
EAR HAEMORRHAGE	0/6441 (0%)	0	1/6446 (0%)	1
SUDDEN HEARING LOSS	1/6441 (0%)	1	0/6446 (0%)	0
TINNITUS	0/6441 (0%)	0	1/6446 (0%)	1
VERTIGO	10/6441 (0.2%)	10	9/6446 (0.1%)	9
VERTIGO POSITIONAL	3/6441 (0%)	3	0/6446 (0%)	0
VESTIBULAR DISORDER	0/6441 (0%)	0	1/6446 (0%)	1
Endocrine disorders
ADRENAL INSUFFICIENCY	1/6441 (0%)	1	0/6446 (0%)	0
GOITRE	0/6441 (0%)	0	1/6446 (0%)	1
HYPERTHYROIDISM	2/6441 (0%)	2	0/6446 (0%)	0
HYPOTHYROIDISM	1/6441 (0%)	1	2/6446 (0%)	2
INAPPROPRIATE ANTIDIURETIC HORMONE SECRETION	0/6441 (0%)	0	1/6446 (0%)	1
TOXIC NODULAR GOITRE	0/6441 (0%)	0	1/6446 (0%)	1
Eye disorders
ABNORMAL SENSATION IN EYE	1/6441 (0%)	1	0/6446 (0%)	0
CATARACT	6/6441 (0.1%)	7	4/6446 (0.1%)	5
CONJUNCTIVITIS	0/6441 (0%)	0	1/6446 (0%)	1
DIPLOPIA	0/6441 (0%)	0	1/6446 (0%)	1
EYE HAEMORRHAGE	1/6441 (0%)	1	0/6446 (0%)	0
GLAUCOMA	2/6441 (0%)	3	0/6446 (0%)	0
MACULAR HOLE	0/6441 (0%)	0	1/6446 (0%)	1
OPTIC ISCHAEMIC NEUROPATHY	0/6441 (0%)	0	1/6446 (0%)	1
RETINAL ARTERY OCCLUSION	1/6441 (0%)	1	2/6446 (0%)	2
RETINAL DETACHMENT	1/6441 (0%)	1	1/6446 (0%)	1
RETINAL VASCULAR THROMBOSIS	1/6441 (0%)	1	0/6446 (0%)	0
STRABISMUS	1/6441 (0%)	1	0/6446 (0%)	0
ULCERATIVE KERATITIS	0/6441 (0%)	0	1/6446 (0%)	1
VISUAL IMPAIRMENT	1/6441 (0%)	1	0/6446 (0%)	0
Gastrointestinal disorders
ABDOMINAL DISCOMFORT	1/6441 (0%)	1	0/6446 (0%)	0
ABDOMINAL HERNIA	1/6441 (0%)	1	0/6446 (0%)	0
ABDOMINAL PAIN	11/6441 (0.2%)	15	11/6446 (0.2%)	12
ABDOMINAL PAIN UPPER	4/6441 (0.1%)	4	9/6446 (0.1%)	9
ABDOMINAL STRANGULATED HERNIA	0/6441 (0%)	0	1/6446 (0%)	1
ABDOMINAL WALL HAEMATOMA	0/6441 (0%)	0	1/6446 (0%)	1
ACUTE ABDOMEN	0/6441 (0%)	0	1/6446 (0%)	1
ANAL FISTULA	1/6441 (0%)	1	0/6446 (0%)	0
ANAL HAEMORRHAGE	1/6441 (0%)	1	0/6446 (0%)	0
ASCITES	2/6441 (0%)	2	0/6446 (0%)	0
COELIAC DISEASE	1/6441 (0%)	3	0/6446 (0%)	0
COLITIS	2/6441 (0%)	2	1/6446 (0%)	1
COLITIS ISCHAEMIC	5/6441 (0.1%)	7	1/6446 (0%)	1
COLITIS ULCERATIVE	1/6441 (0%)	1	0/6446 (0%)	0
COLONIC POLYP	1/6441 (0%)	1	2/6446 (0%)	2
CONSTIPATION	7/6441 (0.1%)	9	6/6446 (0.1%)	6
CROHN'S DISEASE	1/6441 (0%)	3	2/6446 (0%)	2
DIABETIC GASTROPARESIS	1/6441 (0%)	1	0/6446 (0%)	0
DIARRHOEA	5/6441 (0.1%)	6	8/6446 (0.1%)	9
DIARRHOEA HAEMORRHAGIC	0/6441 (0%)	0	1/6446 (0%)	1
DIVERTICULAR PERFORATION	0/6441 (0%)	0	1/6446 (0%)	1
DIVERTICULUM	2/6441 (0%)	2	1/6446 (0%)	1
DIVERTICULUM INTESTINAL	1/6441 (0%)	1	0/6446 (0%)	0
DIVERTICULUM INTESTINAL HAEMORRHAGIC	0/6441 (0%)	0	1/6446 (0%)	1
DUODENAL ULCER	0/6441 (0%)	0	1/6446 (0%)	1
DUODENAL ULCER HAEMORRHAGE	1/6441 (0%)	1	2/6446 (0%)	2
DUODENITIS	0/6441 (0%)	0	1/6446 (0%)	1
DYSPEPSIA	1/6441 (0%)	1	2/6446 (0%)	2
DYSPHAGIA	1/6441 (0%)	1	1/6446 (0%)	1
ENTERITIS	2/6441 (0%)	2	0/6446 (0%)	0
ENTEROVESICAL FISTULA	0/6441 (0%)	0	1/6446 (0%)	1
EROSIVE OESOPHAGITIS	0/6441 (0%)	0	1/6446 (0%)	1
FAECALOMA	1/6441 (0%)	1	2/6446 (0%)	2
FOOD POISONING	0/6441 (0%)	0	2/6446 (0%)	2
GASTRIC HAEMORRHAGE	4/6441 (0.1%)	4	3/6446 (0%)	4
GASTRIC POLYPS	2/6441 (0%)	2	0/6446 (0%)	0
GASTRIC ULCER	7/6441 (0.1%)	8	7/6446 (0.1%)	7
GASTRIC ULCER HAEMORRHAGE	3/6441 (0%)	3	2/6446 (0%)	2
GASTRIC ULCER PERFORATION	1/6441 (0%)	1	0/6446 (0%)	0
GASTRIC VARICES HAEMORRHAGE	0/6441 (0%)	0	1/6446 (0%)	1
GASTRITIS	5/6441 (0.1%)	6	14/6446 (0.2%)	14
GASTRITIS EROSIVE	3/6441 (0%)	3	5/6446 (0.1%)	5
GASTRITIS HAEMORRHAGIC	1/6441 (0%)	1	3/6446 (0%)	3
GASTRODUODENITIS	1/6441 (0%)	1	1/6446 (0%)	1
GASTROINTESTINAL DISORDER	1/6441 (0%)	1	2/6446 (0%)	2
GASTROINTESTINAL EROSION	0/6441 (0%)	0	1/6446 (0%)	1
GASTROINTESTINAL HAEMORRHAGE	13/6441 (0.2%)	13	26/6446 (0.4%)	28
GASTROINTESTINAL NECROSIS	0/6441 (0%)	0	3/6446 (0%)	3
GASTROINTESTINAL PERFORATION	1/6441 (0%)	1	0/6446 (0%)	0
GASTROINTESTINAL ULCER	0/6441 (0%)	0	1/6446 (0%)	1
GASTROOESOPHAGEAL REFLUX DISEASE	10/6441 (0.2%)	10	7/6446 (0.1%)	7
GINGIVAL BLEEDING	0/6441 (0%)	0	1/6446 (0%)	1
HAEMATEMESIS	10/6441 (0.2%)	10	12/6446 (0.2%)	12
HAEMATOCHEZIA	5/6441 (0.1%)	5	10/6446 (0.2%)	10
HAEMORRHAGIC EROSIVE GASTRITIS	1/6441 (0%)	1	0/6446 (0%)	0
HAEMORRHOIDAL HAEMORRHAGE	3/6441 (0%)	3	4/6446 (0.1%)	4
HAEMORRHOIDS	3/6441 (0%)	3	1/6446 (0%)	1
HYPERCHLORHYDRIA	1/6441 (0%)	1	0/6446 (0%)	0
ILEUS	3/6441 (0%)	3	4/6446 (0.1%)	4
ILEUS PARALYTIC	1/6441 (0%)	1	0/6446 (0%)	0
INGUINAL HERNIA	6/6441 (0.1%)	6	16/6446 (0.2%)	16
INGUINAL HERNIA, OBSTRUCTIVE	0/6441 (0%)	0	1/6446 (0%)	1
INTESTINAL HAEMATOMA	0/6441 (0%)	0	1/6446 (0%)	1
INTESTINAL HAEMORRHAGE	0/6441 (0%)	0	1/6446 (0%)	1
INTESTINAL ISCHAEMIA	3/6441 (0%)	3	5/6446 (0.1%)	5
INTESTINAL OBSTRUCTION	4/6441 (0.1%)	4	4/6446 (0.1%)	4
INTESTINAL PERFORATION	1/6441 (0%)	1	0/6446 (0%)	0
LARGE INTESTINAL HAEMORRHAGE	1/6441 (0%)	1	0/6446 (0%)	0
LARGE INTESTINAL OBSTRUCTION	0/6441 (0%)	0	1/6446 (0%)	1
LOCALISED INTRAABDOMINAL FLUID COLLECTION	0/6441 (0%)	0	1/6446 (0%)	1
LOWER GASTROINTESTINAL HAEMORRHAGE	4/6441 (0.1%)	4	3/6446 (0%)	3
MECHANICAL ILEUS	1/6441 (0%)	1	0/6446 (0%)	0
MELAENA	26/6441 (0.4%)	28	38/6446 (0.6%)	40
MESENTERIC VEIN THROMBOSIS	2/6441 (0%)	2	0/6446 (0%)	0
NAUSEA	3/6441 (0%)	3	1/6446 (0%)	1
OESOPHAGEAL PERFORATION	1/6441 (0%)	1	0/6446 (0%)	0
OESOPHAGEAL STENOSIS	0/6441 (0%)	0	2/6446 (0%)	2
OESOPHAGEAL ULCER	1/6441 (0%)	1	0/6446 (0%)	0
OESOPHAGEAL ULCER HAEMORRHAGE	1/6441 (0%)	1	0/6446 (0%)	0
OESOPHAGITIS	0/6441 (0%)	0	5/6446 (0.1%)	5
OESOPHAGITIS HAEMORRHAGIC	1/6441 (0%)	1	0/6446 (0%)	0
PANCREATIC CYST	1/6441 (0%)	1	0/6446 (0%)	0
PANCREATITIS	6/6441 (0.1%)	6	10/6446 (0.2%)	10
PANCREATITIS ACUTE	4/6441 (0.1%)	4	4/6446 (0.1%)	4
PEPTIC ULCER	2/6441 (0%)	2	3/6446 (0%)	3
PERIODONTITIS	0/6441 (0%)	0	1/6446 (0%)	1
PERITONEAL HAEMATOMA	1/6441 (0%)	1	0/6446 (0%)	0
PERITONITIS	1/6441 (0%)	1	0/6446 (0%)	0
PHARYNGOESOPHAGEAL DIVERTICULUM	1/6441 (0%)	1	0/6446 (0%)	0
RECTAL HAEMORRHAGE	22/6441 (0.3%)	22	26/6446 (0.4%)	29
REFLUX OESOPHAGITIS	0/6441 (0%)	0	1/6446 (0%)	1
RETROPERITONEAL FIBROSIS	1/6441 (0%)	1	0/6446 (0%)	0
RETROPERITONEAL HAEMATOMA	1/6441 (0%)	1	0/6446 (0%)	0
RETROPERITONEAL HAEMORRHAGE	6/6441 (0.1%)	6	7/6446 (0.1%)	7
SMALL INTESTINAL HAEMORRHAGE	1/6441 (0%)	1	0/6446 (0%)	0
SMALL INTESTINAL OBSTRUCTION	5/6441 (0.1%)	5	1/6446 (0%)	1
SUBILEUS	1/6441 (0%)	1	0/6446 (0%)	0
TONGUE DISORDER	0/6441 (0%)	0	1/6446 (0%)	1
TOOTHACHE	0/6441 (0%)	0	1/6446 (0%)	1
UMBILICAL HERNIA	2/6441 (0%)	2	1/6446 (0%)	1
UMBILICAL HERNIA, OBSTRUCTIVE	1/6441 (0%)	1	0/6446 (0%)	0
UPPER GASTROINTESTINAL HAEMORRHAGE	6/6441 (0.1%)	7	10/6446 (0.2%)	10
VOMITING	8/6441 (0.1%)	8	3/6446 (0%)	3
General disorders
ASTHENIA	3/6441 (0%)	3	4/6446 (0.1%)	4
BLOODY DISCHARGE	1/6441 (0%)	1	0/6446 (0%)	0
CATHETER SITE HAEMATOMA	16/6441 (0.2%)	16	13/6446 (0.2%)	13
CATHETER SITE HAEMORRHAGE	17/6441 (0.3%)	17	23/6446 (0.4%)	23
CHEST DISCOMFORT	5/6441 (0.1%)	5	6/6446 (0.1%)	6
CHEST PAIN	33/6441 (0.5%)	42	29/6446 (0.4%)	30
CYST	1/6441 (0%)	1	0/6446 (0%)	0
DEVICE BREAKAGE	2/6441 (0%)	2	0/6446 (0%)	0
DEVICE DISLOCATION	1/6441 (0%)	1	2/6446 (0%)	2
DEVICE MALFUNCTION	0/6441 (0%)	0	2/6446 (0%)	2
DRUG INTOLERANCE	1/6441 (0%)	1	0/6446 (0%)	0
EXERCISE TOLERANCE DECREASED	1/6441 (0%)	1	0/6446 (0%)	0
FATIGUE	0/6441 (0%)	0	3/6446 (0%)	3
GAIT DISTURBANCE	1/6441 (0%)	1	0/6446 (0%)	0
GENERAL PHYSICAL HEALTH DETERIORATION	1/6441 (0%)	1	1/6446 (0%)	1
GENERALISED OEDEMA	1/6441 (0%)	1	0/6446 (0%)	0
HERNIA	0/6441 (0%)	0	1/6446 (0%)	1
HERNIA OBSTRUCTIVE	1/6441 (0%)	1	1/6446 (0%)	1
HYPOTHERMIA	0/6441 (0%)	0	1/6446 (0%)	1
IMPAIRED HEALING	1/6441 (0%)	1	6/6446 (0.1%)	6
INFLAMMATION	0/6441 (0%)	0	1/6446 (0%)	1
INFLUENZA LIKE ILLNESS	1/6441 (0%)	1	0/6446 (0%)	0
INJECTION SITE HAEMORRHAGE	1/6441 (0%)	1	1/6446 (0%)	1
LOCAL SWELLING	1/6441 (0%)	1	0/6446 (0%)	0
MALAISE	1/6441 (0%)	1	0/6446 (0%)	0
MEDICAL DEVICE COMPLICATION	1/6441 (0%)	1	0/6446 (0%)	0
MUCOSAL INFLAMMATION	1/6441 (0%)	1	0/6446 (0%)	0
MULTI-ORGAN DISORDER	2/6441 (0%)	2	4/6446 (0.1%)	4
MULTI-ORGAN FAILURE	11/6441 (0.2%)	11	7/6446 (0.1%)	7
NECROSIS	0/6441 (0%)	0	1/6446 (0%)	1
NON-CARDIAC CHEST PAIN	112/6441 (1.7%)	127	141/6446 (2.2%)	158
OEDEMA PERIPHERAL	3/6441 (0%)	3	4/6446 (0.1%)	4
PAIN	1/6441 (0%)	1	1/6446 (0%)	1
POLYP	1/6441 (0%)	1	0/6446 (0%)	0
PUNCTURE SITE REACTION	1/6441 (0%)	1	0/6446 (0%)	0
PYREXIA	6/6441 (0.1%)	6	4/6446 (0.1%)	4
SECRETION DISCHARGE	0/6441 (0%)	0	1/6446 (0%)	1
SENSATION OF PRESSURE	1/6441 (0%)	1	0/6446 (0%)	0
SUDDEN CARDIAC DEATH	1/6441 (0%)	1	0/6446 (0%)	0
THROMBOSIS IN DEVICE	1/6441 (0%)	1	0/6446 (0%)	0
ULCER	1/6441 (0%)	1	0/6446 (0%)	0
Hepatobiliary disorders
ACUTE HEPATIC FAILURE	0/6441 (0%)	0	1/6446 (0%)	1
BILE DUCT OBSTRUCTION	0/6441 (0%)	0	1/6446 (0%)	1
BILE DUCT STONE	2/6441 (0%)	2	4/6446 (0.1%)	4
BILIARY COLIC	2/6441 (0%)	2	1/6446 (0%)	1
BILIARY DYSKINESIA	0/6441 (0%)	0	1/6446 (0%)	1
CHOLANGITIS	0/6441 (0%)	0	1/6446 (0%)	1
CHOLANGITIS ACUTE	1/6441 (0%)	1	0/6446 (0%)	0
CHOLECYSTITIS	18/6441 (0.3%)	18	9/6446 (0.1%)	9
CHOLECYSTITIS ACUTE	10/6441 (0.2%)	10	10/6446 (0.2%)	10
CHOLELITHIASIS	15/6441 (0.2%)	15	13/6446 (0.2%)	13
GALLBLADDER DISORDER	1/6441 (0%)	1	1/6446 (0%)	1
HEPATIC CIRRHOSIS	1/6441 (0%)	1	0/6446 (0%)	0
HEPATIC FAILURE	4/6441 (0.1%)	4	2/6446 (0%)	2
HEPATIC STEATOSIS	1/6441 (0%)	1	0/6446 (0%)	0
HEPATITIS	0/6441 (0%)	0	3/6446 (0%)	3
HEPATITIS ACUTE	2/6441 (0%)	2	0/6446 (0%)	0
HEPATITIS TOXIC	0/6441 (0%)	0	2/6446 (0%)	2
JAUNDICE	0/6441 (0%)	0	1/6446 (0%)	1
LIVER DISORDER	1/6441 (0%)	1	0/6446 (0%)	0
Immune system disorders
ALLERGY TO CHEMICALS	0/6441 (0%)	0	1/6446 (0%)	1
AMYLOIDOSIS	0/6441 (0%)	0	1/6446 (0%)	1
ANAPHYLACTIC REACTION	2/6441 (0%)	2	1/6446 (0%)	1
ANAPHYLACTIC SHOCK	0/6441 (0%)	0	1/6446 (0%)	1
ANTIPHOSPHOLIPID SYNDROME	1/6441 (0%)	1	0/6446 (0%)	0
CONTRAST MEDIA ALLERGY	0/6441 (0%)	0	1/6446 (0%)	1
DRUG HYPERSENSITIVITY	1/6441 (0%)	1	1/6446 (0%)	1
HYPERSENSITIVITY	1/6441 (0%)	1	3/6446 (0%)	3
SARCOIDOSIS	1/6441 (0%)	1	0/6446 (0%)	0
Infections and infestations
ABDOMINAL ABSCESS	2/6441 (0%)	2	3/6446 (0%)	3
ABDOMINAL INFECTION	1/6441 (0%)	1	1/6446 (0%)	1
ABDOMINAL SEPSIS	0/6441 (0%)	0	1/6446 (0%)	1
ABSCESS	1/6441 (0%)	1	0/6446 (0%)	0
ABSCESS LIMB	1/6441 (0%)	1	0/6446 (0%)	0
ABSCESS ORAL	0/6441 (0%)	0	1/6446 (0%)	1
ANAL ABSCESS	2/6441 (0%)	3	4/6446 (0.1%)	4
APPENDICITIS	4/6441 (0.1%)	4	9/6446 (0.1%)	9
APPENDICITIS PERFORATED	2/6441 (0%)	2	0/6446 (0%)	0
ARTERIOVENOUS GRAFT SITE INFECTION	0/6441 (0%)	0	1/6446 (0%)	1
ARTERITIS INFECTIVE	1/6441 (0%)	1	0/6446 (0%)	0
ARTHRITIS INFECTIVE	2/6441 (0%)	2	0/6446 (0%)	0
BACTERAEMIA	1/6441 (0%)	1	2/6446 (0%)	2
BACTERIAL INFECTION	1/6441 (0%)	1	0/6446 (0%)	0
BACTERIAL SEPSIS	1/6441 (0%)	1	1/6446 (0%)	1
BORRELIA INFECTION	1/6441 (0%)	1	1/6446 (0%)	1
BRONCHITIS	11/6441 (0.2%)	12	18/6446 (0.3%)	18
BRONCHITIS VIRAL	0/6441 (0%)	0	1/6446 (0%)	1
BRONCHOPNEUMONIA	4/6441 (0.1%)	4	2/6446 (0%)	2
CELLULITIS	16/6441 (0.2%)	16	25/6446 (0.4%)	26
CHEST WALL ABSCESS	0/6441 (0%)	0	1/6446 (0%)	1
CHOLECYSTITIS INFECTIVE	0/6441 (0%)	0	1/6446 (0%)	1
CLOSTRIDIAL INFECTION	2/6441 (0%)	2	0/6446 (0%)	0
CLOSTRIDIUM DIFFICILE COLITIS	1/6441 (0%)	1	0/6446 (0%)	0
CYSTITIS	2/6441 (0%)	2	2/6446 (0%)	2
CYTOMEGALOVIRUS INFECTION	1/6441 (0%)	1	0/6446 (0%)	0
DEVICE RELATED INFECTION	2/6441 (0%)	2	0/6446 (0%)	0
DIABETIC FOOT INFECTION	0/6441 (0%)	0	1/6446 (0%)	1
DIVERTICULITIS	8/6441 (0.1%)	9	13/6446 (0.2%)	14
ENDOCARDITIS	3/6441 (0%)	3	2/6446 (0%)	2
ENTEROCOCCAL INFECTION	0/6441 (0%)	0	1/6446 (0%)	1
ENTEROCOCCAL SEPSIS	0/6441 (0%)	0	1/6446 (0%)	1
ERYSIPELAS	5/6441 (0.1%)	5	3/6446 (0%)	4
ESCHERICHIA SEPSIS	0/6441 (0%)	0	1/6446 (0%)	1
ESCHERICHIA URINARY TRACT INFECTION	0/6441 (0%)	0	1/6446 (0%)	1
EYE INFECTION	0/6441 (0%)	0	1/6446 (0%)	1
GANGRENE	4/6441 (0.1%)	5	0/6446 (0%)	0
GASTROENTERITIS	8/6441 (0.1%)	9	12/6446 (0.2%)	13
GASTROENTERITIS NOROVIRUS	1/6441 (0%)	1	0/6446 (0%)	0
GASTROENTERITIS SALMONELLA	0/6441 (0%)	0	1/6446 (0%)	1
GASTROENTERITIS VIRAL	3/6441 (0%)	3	4/6446 (0.1%)	4
GRAFT INFECTION	0/6441 (0%)	0	2/6446 (0%)	2
GROIN ABSCESS	0/6441 (0%)	0	1/6446 (0%)	1
GROIN INFECTION	0/6441 (0%)	0	1/6446 (0%)	1
H1N1 INFLUENZA	0/6441 (0%)	0	1/6446 (0%)	1
HAEMATOMA INFECTION	2/6441 (0%)	2	1/6446 (0%)	1
HEPATITIS B	0/6441 (0%)	0	1/6446 (0%)	1
HEPATITIS C	0/6441 (0%)	0	1/6446 (0%)	1
HERPES SIMPLEX	0/6441 (0%)	0	1/6446 (0%)	1
HERPES ZOSTER	1/6441 (0%)	1	3/6446 (0%)	3
HIV INFECTION	0/6441 (0%)	0	1/6446 (0%)	1
IMPLANT SITE INFECTION	1/6441 (0%)	1	0/6446 (0%)	0
INCISION SITE INFECTION	3/6441 (0%)	3	2/6446 (0%)	2
INFECTED CYST	1/6441 (0%)	1	0/6446 (0%)	0
INFECTED SEBACEOUS CYST	0/6441 (0%)	0	1/6446 (0%)	1
INFECTED SKIN ULCER	0/6441 (0%)	0	1/6446 (0%)	1
INFECTION	3/6441 (0%)	3	0/6446 (0%)	0
INFECTIVE EXACERBATION OF CHRONIC OBSTRUCTIVE AIRWAYS DISEASE	1/6441 (0%)	1	1/6446 (0%)	2
INFLUENZA	1/6441 (0%)	1	2/6446 (0%)	2
INJECTION SITE ABSCESS	1/6441 (0%)	1	0/6446 (0%)	0
INTERVERTEBRAL DISCITIS	0/6441 (0%)	0	1/6446 (0%)	1
KIDNEY INFECTION	0/6441 (0%)	0	1/6446 (0%)	1
LEISHMANIASIS	0/6441 (0%)	0	1/6446 (0%)	1
LEPROSY	0/6441 (0%)	0	1/6446 (0%)	1
LIP INFECTION	0/6441 (0%)	0	1/6446 (0%)	1
LOBAR PNEUMONIA	5/6441 (0.1%)	5	6/6446 (0.1%)	6
LOCALISED INFECTION	1/6441 (0%)	1	4/6446 (0.1%)	4
LOWER RESPIRATORY TRACT INFECTION	3/6441 (0%)	3	3/6446 (0%)	3
LUNG INFECTION	6/6441 (0.1%)	6	1/6446 (0%)	1
LUNG INFECTION PSEUDOMONAL	1/6441 (0%)	1	0/6446 (0%)	0
LYMPH NODE ABSCESS	0/6441 (0%)	0	1/6446 (0%)	1
MEDIASTINITIS	4/6441 (0.1%)	4	5/6446 (0.1%)	5
MENINGITIS ASEPTIC	0/6441 (0%)	0	1/6446 (0%)	1
METAPNEUMOVIRUS INFECTION	0/6441 (0%)	0	1/6446 (0%)	1
NECROTISING FASCIITIS	1/6441 (0%)	1	0/6446 (0%)	0
NOCARDIOSIS	0/6441 (0%)	0	1/6446 (0%)	1
ORCHITIS	1/6441 (0%)	1	0/6446 (0%)	0
OSTEOMYELITIS	7/6441 (0.1%)	7	6/6446 (0.1%)	6
OSTEOMYELITIS CHRONIC	1/6441 (0%)	1	1/6446 (0%)	1
OTITIS MEDIA	1/6441 (0%)	1	0/6446 (0%)	0
OTITIS MEDIA CHRONIC	1/6441 (0%)	1	0/6446 (0%)	0
PELVIC ABSCESS	0/6441 (0%)	0	1/6446 (0%)	1
PERICARDITIS TUBERCULOUS	0/6441 (0%)	0	1/6446 (0%)	1
PERIDIVERTICULAR ABSCESS	0/6441 (0%)	0	1/6446 (0%)	1
PERIRECTAL ABSCESS	2/6441 (0%)	2	0/6446 (0%)	0
PERITONEAL ABSCESS	1/6441 (0%)	1	1/6446 (0%)	1
PNEUMONIA	83/6441 (1.3%)	93	100/6446 (1.6%)	111
PNEUMONIA BACTERIAL	1/6441 (0%)	1	0/6446 (0%)	0
PNEUMONIA HAEMOPHILUS	0/6441 (0%)	0	1/6446 (0%)	1
PNEUMONIA INFLUENZAL	0/6441 (0%)	0	1/6446 (0%)	1
PNEUMONIA KLEBSIELLA	0/6441 (0%)	0	1/6446 (0%)	1
PNEUMONIA PNEUMOCOCCAL	1/6441 (0%)	1	0/6446 (0%)	0
PNEUMONIA PRIMARY ATYPICAL	1/6441 (0%)	1	0/6446 (0%)	0
POST PROCEDURAL INFECTION	3/6441 (0%)	4	3/6446 (0%)	3
POSTOPERATIVE WOUND INFECTION	6/6441 (0.1%)	6	9/6446 (0.1%)	9
PSEUDOMEMBRANOUS COLITIS	0/6441 (0%)	0	1/6446 (0%)	2
PSEUDOMONAS BRONCHITIS	0/6441 (0%)	0	1/6446 (0%)	1
PSOAS ABSCESS	0/6441 (0%)	0	1/6446 (0%)	1
PYELONEPHRITIS	5/6441 (0.1%)	5	1/6446 (0%)	1
PYOTHORAX	1/6441 (0%)	1	1/6446 (0%)	1
RESPIRATORY TRACT INFECTION	7/6441 (0.1%)	7	4/6446 (0.1%)	4
RESPIRATORY TRACT INFECTION VIRAL	1/6441 (0%)	1	0/6446 (0%)	0
SCROTAL ABSCESS	0/6441 (0%)	0	1/6446 (0%)	1
SEPSIS	23/6441 (0.4%)	23	24/6446 (0.4%)	25
SEPTIC SHOCK	18/6441 (0.3%)	18	11/6446 (0.2%)	11
SERRATIA INFECTION	1/6441 (0%)	1	0/6446 (0%)	0
SHUNT INFECTION	0/6441 (0%)	0	1/6446 (0%)	1
SIALOADENITIS	1/6441 (0%)	1	0/6446 (0%)	0
SINUSITIS	2/6441 (0%)	2	0/6446 (0%)	0
SKIN INFECTION	1/6441 (0%)	1	3/6446 (0%)	3
SMALL INTESTINE GANGRENE	1/6441 (0%)	1	0/6446 (0%)	0
STAPHYLOCOCCAL ABSCESS	0/6441 (0%)	0	1/6446 (0%)	1
STAPHYLOCOCCAL BACTERAEMIA	1/6441 (0%)	1	0/6446 (0%)	0
STAPHYLOCOCCAL INFECTION	2/6441 (0%)	2	3/6446 (0%)	3
STAPHYLOCOCCAL MEDIASTINITIS	1/6441 (0%)	1	0/6446 (0%)	0
STAPHYLOCOCCAL SEPSIS	1/6441 (0%)	1	0/6446 (0%)	0
STERNITIS	0/6441 (0%)	0	1/6446 (0%)	1
STITCH ABSCESS	1/6441 (0%)	1	0/6446 (0%)	0
STREPTOCOCCAL SEPSIS	0/6441 (0%)	0	1/6446 (0%)	1
UPPER RESPIRATORY TRACT INFECTION	6/6441 (0.1%)	6	3/6446 (0%)	3
URINARY TRACT INFECTION	26/6441 (0.4%)	27	23/6446 (0.4%)	25
UROSEPSIS	2/6441 (0%)	2	8/6446 (0.1%)	8
VESTIBULAR NEURONITIS	1/6441 (0%)	1	2/6446 (0%)	2
VIRAL INFECTION	3/6441 (0%)	3	2/6446 (0%)	2
VIRAL UPPER RESPIRATORY TRACT INFECTION	2/6441 (0%)	2	0/6446 (0%)	0
WOUND INFECTION	12/6441 (0.2%)	12	7/6446 (0.1%)	7
WOUND INFECTION STAPHYLOCOCCAL	1/6441 (0%)	2	0/6446 (0%)	0
WOUND SEPSIS	0/6441 (0%)	0	1/6446 (0%)	1
Injury, poisoning and procedural complications
ABDOMINAL INJURY	0/6441 (0%)	0	1/6446 (0%)	1
ABDOMINAL WOUND DEHISCENCE	0/6441 (0%)	0	1/6446 (0%)	1
ACCIDENTAL OVERDOSE	0/6441 (0%)	0	1/6446 (0%)	1
ALCOHOL POISONING	4/6441 (0.1%)	4	2/6446 (0%)	2
ANAEMIA POSTOPERATIVE	3/6441 (0%)	3	0/6446 (0%)	0
ANKLE FRACTURE	3/6441 (0%)	3	3/6446 (0%)	3
ARTERIAL INJURY	0/6441 (0%)	0	1/6446 (0%)	1
ARTERIOVENOUS FISTULA SITE HAEMORRHAGE	0/6441 (0%)	0	1/6446 (0%)	1
BACK INJURY	0/6441 (0%)	0	1/6446 (0%)	1
CARDIAC PROCEDURE COMPLICATION	1/6441 (0%)	1	0/6446 (0%)	0
CARDIAC VALVE RUPTURE	0/6441 (0%)	0	1/6446 (0%)	1
CEREBRAL HAEMORRHAGE TRAUMATIC	1/6441 (0%)	1	0/6446 (0%)	0
CLAVICLE FRACTURE	1/6441 (0%)	1	0/6446 (0%)	0
COLLAPSE OF LUNG	0/6441 (0%)	0	1/6446 (0%)	1
COMMINUTED FRACTURE	0/6441 (0%)	0	1/6446 (0%)	1
CONCUSSION	3/6441 (0%)	3	0/6446 (0%)	0
CONFUSION POSTOPERATIVE	0/6441 (0%)	0	1/6446 (0%)	1
CONTUSION	1/6441 (0%)	1	6/6446 (0.1%)	8
CRUSH INJURY	0/6441 (0%)	0	1/6446 (0%)	1
EXTRADURAL HAEMATOMA	0/6441 (0%)	0	1/6446 (0%)	1
FACE INJURY	1/6441 (0%)	1	0/6446 (0%)	0
FACIAL BONES FRACTURE	0/6441 (0%)	0	3/6446 (0%)	3
FALL	16/6441 (0.2%)	16	22/6446 (0.3%)	22
FEMORAL NECK FRACTURE	2/6441 (0%)	2	4/6446 (0.1%)	4
FEMUR FRACTURE	4/6441 (0.1%)	4	9/6446 (0.1%)	9
FIBULA FRACTURE	0/6441 (0%)	0	1/6446 (0%)	1
FOOT FRACTURE	3/6441 (0%)	3	2/6446 (0%)	2
FOREARM FRACTURE	0/6441 (0%)	0	1/6446 (0%)	1
GASTROINTESTINAL STOMA COMPLICATION	0/6441 (0%)	0	1/6446 (0%)	1
GUN SHOT WOUND	0/6441 (0%)	0	1/6446 (0%)	1
HEAD INJURY	3/6441 (0%)	3	4/6446 (0.1%)	4
HEPATIC HAEMATOMA	0/6441 (0%)	0	1/6446 (0%)	1
HEPATIC RUPTURE	1/6441 (0%)	1	0/6446 (0%)	0
HIP FRACTURE	5/6441 (0.1%)	5	7/6446 (0.1%)	7
HUMERUS FRACTURE	3/6441 (0%)	3	4/6446 (0.1%)	4
INCISION SITE COMPLICATION	0/6441 (0%)	0	1/6446 (0%)	1
INCISION SITE HAEMORRHAGE	0/6441 (0%)	0	1/6446 (0%)	1
INCISIONAL HERNIA	1/6441 (0%)	1	0/6446 (0%)	0
INFLAMMATION OF WOUND	0/6441 (0%)	0	1/6446 (0%)	1
JOINT DISLOCATION	2/6441 (0%)	2	0/6446 (0%)	0
LACERATION	1/6441 (0%)	1	1/6446 (0%)	1
LIMB INJURY	1/6441 (0%)	1	2/6446 (0%)	2
LIMB TRAUMATIC AMPUTATION	1/6441 (0%)	1	0/6446 (0%)	0
LUMBAR VERTEBRAL FRACTURE	0/6441 (0%)	0	3/6446 (0%)	3
MENISCUS LESION	1/6441 (0%)	1	1/6446 (0%)	1
MULTIPLE FRACTURES	2/6441 (0%)	2	0/6446 (0%)	0
MUSCLE STRAIN	1/6441 (0%)	1	0/6446 (0%)	0
OPEN FRACTURE	0/6441 (0%)	0	1/6446 (0%)	1
OPERATIVE HAEMORRHAGE	11/6441 (0.2%)	12	10/6446 (0.2%)	10
OVERDOSE	2/6441 (0%)	2	4/6446 (0.1%)	4
PATELLA FRACTURE	0/6441 (0%)	0	2/6446 (0%)	2
PELVIC FRACTURE	1/6441 (0%)	1	1/6446 (0%)	1
PERIPROSTHETIC FRACTURE	0/6441 (0%)	0	1/6446 (0%)	1
POST PROCEDURAL COMPLICATION	6/6441 (0.1%)	6	3/6446 (0%)	3
POST PROCEDURAL DISCHARGE	1/6441 (0%)	1	0/6446 (0%)	0
POST PROCEDURAL HAEMATOMA	1/6441 (0%)	1	1/6446 (0%)	1
POST PROCEDURAL HAEMORRHAGE	91/6441 (1.4%)	91	112/6446 (1.7%)	114
POSTOPERATIVE HERNIA	0/6441 (0%)	0	1/6446 (0%)	1
POSTOPERATIVE ILEUS	0/6441 (0%)	0	1/6446 (0%)	1
POSTOPERATIVE THORACIC PROCEDURE COMPLICATION	5/6441 (0.1%)	5	4/6446 (0.1%)	4
POSTOPERATIVE WOUND COMPLICATION	1/6441 (0%)	1	0/6446 (0%)	0
POSTPERICARDIOTOMY SYNDROME	4/6441 (0.1%)	4	3/6446 (0%)	3
PROCEDURAL PAIN	1/6441 (0%)	1	2/6446 (0%)	2
PUBIS FRACTURE	2/6441 (0%)	2	0/6446 (0%)	0
RADIUS FRACTURE	3/6441 (0%)	3	2/6446 (0%)	2
RIB FRACTURE	0/6441 (0%)	0	3/6446 (0%)	3
ROAD TRAFFIC ACCIDENT	2/6441 (0%)	2	7/6446 (0.1%)	8
SHUNT MALFUNCTION	0/6441 (0%)	0	1/6446 (0%)	1
SKULL FRACTURE	1/6441 (0%)	1	1/6446 (0%)	1
SKULL FRACTURED BASE	1/6441 (0%)	1	0/6446 (0%)	0
SOFT TISSUE INJURY	0/6441 (0%)	0	1/6446 (0%)	1
SPINAL COMPRESSION FRACTURE	2/6441 (0%)	2	2/6446 (0%)	3
SPINAL FRACTURE	0/6441 (0%)	0	1/6446 (0%)	1
SPLENIC RUPTURE	1/6441 (0%)	1	0/6446 (0%)	0
STAB WOUND	0/6441 (0%)	0	1/6446 (0%)	1
STERNAL FRACTURE	1/6441 (0%)	1	0/6446 (0%)	0
SUBDURAL HAEMATOMA	2/6441 (0%)	2	9/6446 (0.1%)	9
SUBDURAL HAEMORRHAGE	0/6441 (0%)	0	2/6446 (0%)	2
TENDON INJURY	0/6441 (0%)	0	1/6446 (0%)	1
TENDON RUPTURE	3/6441 (0%)	3	1/6446 (0%)	1
THERMAL BURN	0/6441 (0%)	0	1/6446 (0%)	1
TIBIA FRACTURE	1/6441 (0%)	1	2/6446 (0%)	2
TOXICITY TO VARIOUS AGENTS	5/6441 (0.1%)	5	0/6446 (0%)	0
TRANSPLANT FAILURE	0/6441 (0%)	0	1/6446 (0%)	1
TRAUMATIC LIVER INJURY	1/6441 (0%)	1	0/6446 (0%)	0
TRAUMATIC LUNG INJURY	0/6441 (0%)	0	1/6446 (0%)	1
UPPER LIMB FRACTURE	1/6441 (0%)	1	4/6446 (0.1%)	4
URINARY RETENTION POSTOPERATIVE	0/6441 (0%)	0	1/6446 (0%)	1
VASCULAR PROCEDURE COMPLICATION	1/6441 (0%)	1	1/6446 (0%)	1
VASCULAR PSEUDOANEURYSM	5/6441 (0.1%)	5	17/6446 (0.3%)	17
VASOPLEGIA SYNDROME	1/6441 (0%)	1	0/6446 (0%)	0
VENA CAVA INJURY	1/6441 (0%)	1	0/6446 (0%)	0
WOUND	1/6441 (0%)	1	2/6446 (0%)	2
WOUND COMPLICATION	0/6441 (0%)	0	2/6446 (0%)	2
WOUND DEHISCENCE	4/6441 (0.1%)	4	0/6446 (0%)	0
WOUND HAEMORRHAGE	3/6441 (0%)	3	2/6446 (0%)	2
WOUND SECRETION	1/6441 (0%)	1	1/6446 (0%)	1
WRIST FRACTURE	6/6441 (0.1%)	6	0/6446 (0%)	0
Investigations
ACTIVATED PARTIAL THROMBOPLASTIN TIME PROLONGED	1/6441 (0%)	1	0/6446 (0%)	0
ALANINE AMINOTRANSFERASE INCREASED	0/6441 (0%)	0	1/6446 (0%)	1
BLEEDING TIME PROLONGED	1/6441 (0%)	1	1/6446 (0%)	1
BLOOD ALKALINE PHOSPHATASE INCREASED	1/6441 (0%)	1	0/6446 (0%)	0
BLOOD BILIRUBIN INCREASED	0/6441 (0%)	0	1/6446 (0%)	1
BLOOD CREATINE PHOSPHOKINASE INCREASED	0/6441 (0%)	0	1/6446 (0%)	1
BLOOD CREATINE PHOSPHOKINASE MB INCREASED	0/6441 (0%)	0	1/6446 (0%)	1
BLOOD CREATININE INCREASED	1/6441 (0%)	1	1/6446 (0%)	1
BLOOD CULTURE POSITIVE	1/6441 (0%)	1	0/6446 (0%)	0
BLOOD GLUCOSE ABNORMAL	0/6441 (0%)	0	1/6446 (0%)	1
BLOOD GLUCOSE INCREASED	3/6441 (0%)	3	1/6446 (0%)	2
BLOOD POTASSIUM DECREASED	0/6441 (0%)	0	1/6446 (0%)	1
BLOOD PRESSURE INCREASED	0/6441 (0%)	0	1/6446 (0%)	1
C-REACTIVE PROTEIN INCREASED	1/6441 (0%)	1	1/6446 (0%)	1
CARDIAC MONITORING ABNORMAL	0/6441 (0%)	0	1/6446 (0%)	1
CAROTID BRUIT	0/6441 (0%)	0	1/6446 (0%)	1
EJECTION FRACTION DECREASED	3/6441 (0%)	3	2/6446 (0%)	2
ELECTROCARDIOGRAM QRS COMPLEX PROLONGED	1/6441 (0%)	1	1/6446 (0%)	1
GAMMA-GLUTAMYLTRANSFERASE INCREASED	3/6441 (0%)	3	0/6446 (0%)	0
HAEMOGLOBIN DECREASED	11/6441 (0.2%)	11	12/6446 (0.2%)	12
HEART RATE IRREGULAR	1/6441 (0%)	1	0/6446 (0%)	0
HEPATIC ENZYME INCREASED	4/6441 (0.1%)	4	4/6446 (0.1%)	4
LIPOPROTEIN (A) INCREASED	0/6441 (0%)	0	1/6446 (0%)	1
LIVER FUNCTION TEST ABNORMAL	2/6441 (0%)	2	1/6446 (0%)	1
OCCULT BLOOD POSITIVE	0/6441 (0%)	0	3/6446 (0%)	3
PLATELET COUNT DECREASED	4/6441 (0.1%)	5	4/6446 (0.1%)	4
TRANSAMINASES INCREASED	0/6441 (0%)	0	1/6446 (0%)	1
TROPONIN INCREASED	1/6441 (0%)	1	0/6446 (0%)	0
URINE OUTPUT DECREASED	0/6441 (0%)	0	1/6446 (0%)	1
WEIGHT DECREASED	0/6441 (0%)	0	2/6446 (0%)	2
WEIGHT INCREASED	1/6441 (0%)	1	0/6446 (0%)	0
Metabolism and nutrition disorders
CACHEXIA	0/6441 (0%)	0	1/6446 (0%)	1
DEHYDRATION	10/6441 (0.2%)	10	7/6446 (0.1%)	9
DIABETES MELLITUS	11/6441 (0.2%)	13	6/6446 (0.1%)	6
DIABETES MELLITUS INADEQUATE CONTROL	5/6441 (0.1%)	5	9/6446 (0.1%)	9
DIABETIC FOOT	2/6441 (0%)	2	3/6446 (0%)	3
DIABETIC KETOACIDOSIS	4/6441 (0.1%)	4	3/6446 (0%)	8
ELECTROLYTE IMBALANCE	0/6441 (0%)	0	1/6446 (0%)	1
FAILURE TO THRIVE	2/6441 (0%)	2	1/6446 (0%)	1
FLUID OVERLOAD	6/6441 (0.1%)	7	2/6446 (0%)	2
FLUID RETENTION	1/6441 (0%)	1	0/6446 (0%)	0
GOUT	2/6441 (0%)	2	2/6446 (0%)	2
HYPERGLYCAEMIA	8/6441 (0.1%)	8	7/6446 (0.1%)	7
HYPERGLYCAEMIC HYPEROSMOLAR NONKETOTIC SYNDROME	1/6441 (0%)	1	0/6446 (0%)	0
HYPERKALAEMIA	9/6441 (0.1%)	10	5/6446 (0.1%)	5
HYPOCALCAEMIA	1/6441 (0%)	1	1/6446 (0%)	1
HYPOGLYCAEMIA	11/6441 (0.2%)	11	10/6446 (0.2%)	12
HYPOGLYCAEMIC UNCONSCIOUSNESS	1/6441 (0%)	1	0/6446 (0%)	0
HYPOKALAEMIA	2/6441 (0%)	2	2/6446 (0%)	2
HYPONATRAEMIA	4/6441 (0.1%)	4	4/6446 (0.1%)	4
IRON DEFICIENCY	1/6441 (0%)	1	0/6446 (0%)	0
LACTIC ACIDOSIS	1/6441 (0%)	1	0/6446 (0%)	0
OBESITY	0/6441 (0%)	0	1/6446 (0%)	1
TYPE 2 DIABETES MELLITUS	1/6441 (0%)	1	0/6446 (0%)	0
Musculoskeletal and connective tissue disorders
ARTHRALGIA	5/6441 (0.1%)	5	4/6446 (0.1%)	4
ARTHRITIS	4/6441 (0.1%)	4	5/6446 (0.1%)	5
ARTHRITIS REACTIVE	1/6441 (0%)	1	0/6446 (0%)	0
ARTHROPATHY	1/6441 (0%)	1	1/6446 (0%)	1
ARTICULAR CALCIFICATION	1/6441 (0%)	1	0/6446 (0%)	0
BACK PAIN	8/6441 (0.1%)	8	8/6446 (0.1%)	8
BONE PAIN	1/6441 (0%)	1	0/6446 (0%)	0
BURSITIS	1/6441 (0%)	1	0/6446 (0%)	0
CERVICAL SPINAL STENOSIS	2/6441 (0%)	2	0/6446 (0%)	0
CHONDRITIS	0/6441 (0%)	0	1/6446 (0%)	1
COMPARTMENT SYNDROME	0/6441 (0%)	0	1/6446 (0%)	1
CRYSTAL ARTHROPATHY	0/6441 (0%)	0	1/6446 (0%)	1
GROIN PAIN	1/6441 (0%)	1	0/6446 (0%)	0
HAEMARTHROSIS	1/6441 (0%)	1	0/6446 (0%)	0
INTERVERTEBRAL DISC PROTRUSION	9/6441 (0.1%)	9	3/6446 (0%)	3
JOINT EFFUSION	1/6441 (0%)	1	1/6446 (0%)	1
KYPHOSIS	1/6441 (0%)	1	0/6446 (0%)	0
LUMBAR SPINAL STENOSIS	0/6441 (0%)	0	4/6446 (0.1%)	4
MUSCLE HAEMORRHAGE	0/6441 (0%)	0	1/6446 (0%)	1
MUSCLE TIGHTNESS	1/6441 (0%)	1	0/6446 (0%)	0
MUSCULAR WEAKNESS	1/6441 (0%)	1	0/6446 (0%)	0
MUSCULOSKELETAL CHEST PAIN	19/6441 (0.3%)	19	14/6446 (0.2%)	16
MUSCULOSKELETAL PAIN	5/6441 (0.1%)	5	10/6446 (0.2%)	10
MYALGIA	4/6441 (0.1%)	4	4/6446 (0.1%)	6
MYALGIA INTERCOSTAL	0/6441 (0%)	0	1/6446 (0%)	1
MYOPATHY	1/6441 (0%)	1	1/6446 (0%)	1
MYOSCLEROSIS	0/6441 (0%)	0	1/6446 (0%)	1
NECK PAIN	5/6441 (0.1%)	5	2/6446 (0%)	2
OSTEOARTHRITIS	22/6441 (0.3%)	22	16/6446 (0.2%)	16
OSTEONECROSIS	0/6441 (0%)	0	1/6446 (0%)	1
PAIN IN EXTREMITY	2/6441 (0%)	3	4/6446 (0.1%)	5
POLYARTHRITIS	0/6441 (0%)	0	1/6446 (0%)	1
RHABDOMYOLYSIS	3/6441 (0%)	3	0/6446 (0%)	0
RHEUMATOID ARTHRITIS	3/6441 (0%)	3	1/6446 (0%)	1
ROTATOR CUFF SYNDROME	2/6441 (0%)	2	1/6446 (0%)	1
SCOLIOSIS	1/6441 (0%)	1	0/6446 (0%)	0
SPINAL COLUMN STENOSIS	3/6441 (0%)	3	2/6446 (0%)	2
SPINAL DISORDER	0/6441 (0%)	0	1/6446 (0%)	1
SPONDYLOLISTHESIS	2/6441 (0%)	2	1/6446 (0%)	1
SYMPATHETIC POSTERIOR CERVICAL SYNDROME	1/6441 (0%)	1	0/6446 (0%)	0
SYNOVIAL CYST	1/6441 (0%)	1	0/6446 (0%)	0
TENDONITIS	0/6441 (0%)	0	1/6446 (0%)	1
TRIGGER FINGER	1/6441 (0%)	1	0/6446 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
ABDOMINAL NEOPLASM	0/6441 (0%)	0	1/6446 (0%)	1
ADENOCARCINOMA	1/6441 (0%)	1	0/6446 (0%)	0
ADRENAL ADENOMA	1/6441 (0%)	1	0/6446 (0%)	0
ADRENAL NEOPLASM	0/6441 (0%)	0	1/6446 (0%)	1
B-CELL LYMPHOMA	1/6441 (0%)	1	1/6446 (0%)	1
BASAL CELL CARCINOMA	2/6441 (0%)	3	3/6446 (0%)	3
BENIGN LUNG NEOPLASM	1/6441 (0%)	1	0/6446 (0%)	0
BENIGN NEOPLASM	1/6441 (0%)	1	0/6446 (0%)	0
BENIGN NEOPLASM OF BLADDER	1/6441 (0%)	1	0/6446 (0%)	0
BENIGN OESOPHAGEAL NEOPLASM	0/6441 (0%)	0	1/6446 (0%)	1
BILE DUCT CANCER	2/6441 (0%)	2	1/6446 (0%)	1
BLADDER CANCER	5/6441 (0.1%)	5	9/6446 (0.1%)	9
BLADDER NEOPLASM	2/6441 (0%)	2	4/6446 (0.1%)	5
BLADDER TRANSITIONAL CELL CARCINOMA	0/6441 (0%)	0	1/6446 (0%)	1
BRAIN NEOPLASM BENIGN	1/6441 (0%)	1	0/6446 (0%)	0
BREAST CANCER	2/6441 (0%)	2	3/6446 (0%)	3
BREAST NEOPLASM	1/6441 (0%)	1	0/6446 (0%)	0
BRONCHIAL CARCINOMA	2/6441 (0%)	2	1/6446 (0%)	1
CANCER PAIN	0/6441 (0%)	0	1/6446 (0%)	1
CARDIAC VALVE FIBROELASTOMA	1/6441 (0%)	1	0/6446 (0%)	0
CEREBRAL HAEMANGIOMA	0/6441 (0%)	0	1/6446 (0%)	1
CHRONIC LYMPHOCYTIC LEUKAEMIA	2/6441 (0%)	2	0/6446 (0%)	0
CHRONIC MYELOMONOCYTIC LEUKAEMIA	1/6441 (0%)	1	0/6446 (0%)	0
COLON ADENOMA	1/6441 (0%)	1	0/6446 (0%)	0
COLON CANCER	10/6441 (0.2%)	10	20/6446 (0.3%)	20
COLON CANCER STAGE II	1/6441 (0%)	1	0/6446 (0%)	0
COLON CANCER STAGE III	0/6441 (0%)	0	1/6446 (0%)	1
COLON NEOPLASM	1/6441 (0%)	1	2/6446 (0%)	2
COLORECTAL CANCER	1/6441 (0%)	1	0/6446 (0%)	0
ENDOMETRIAL CANCER	1/6441 (0%)	1	1/6446 (0%)	1
ENDOMETRIAL CANCER STAGE I	0/6441 (0%)	0	2/6446 (0%)	2
ENDOMETRIAL NEOPLASM	0/6441 (0%)	0	1/6446 (0%)	1
FIBROMA	0/6441 (0%)	0	1/6446 (0%)	1
GASTRIC CANCER	7/6441 (0.1%)	7	4/6446 (0.1%)	4
GASTRIC CANCER STAGE 0	0/6441 (0%)	0	1/6446 (0%)	1
GASTRIC NEOPLASM	0/6441 (0%)	0	1/6446 (0%)	1
GASTROINTESTINAL CANCER METASTATIC	1/6441 (0%)	1	0/6446 (0%)	0
GASTROINTESTINAL TRACT ADENOMA	0/6441 (0%)	0	2/6446 (0%)	2
GASTROOESOPHAGEAL CANCER	1/6441 (0%)	1	0/6446 (0%)	0
HEPATIC NEOPLASM MALIGNANT	2/6441 (0%)	2	1/6446 (0%)	1
HODGKIN'S DISEASE	0/6441 (0%)	0	1/6446 (0%)	1
HODGKIN'S DISEASE MIXED CELLULARITY STAGE UNSPECIFIED	0/6441 (0%)	0	1/6446 (0%)	1
INTESTINAL ADENOCARCINOMA	0/6441 (0%)	0	1/6446 (0%)	1
INTRAOCULAR MELANOMA	0/6441 (0%)	0	1/6446 (0%)	1
IRITIC MELANOMA	0/6441 (0%)	0	1/6446 (0%)	1
LARGE CELL CARCINOMA OF THE RESPIRATORY TRACT STAGE UNSPECIFIED	0/6441 (0%)	0	1/6446 (0%)	1
LARYNGEAL CANCER	1/6441 (0%)	1	1/6446 (0%)	1
LIPOMA	0/6441 (0%)	0	1/6446 (0%)	1
LUNG ADENOCARCINOMA	3/6441 (0%)	3	1/6446 (0%)	1
LUNG ADENOCARCINOMA METASTATIC	0/6441 (0%)	0	1/6446 (0%)	1
LUNG CANCER METASTATIC	0/6441 (0%)	0	2/6446 (0%)	2
LUNG CARCINOMA CELL TYPE UNSPECIFIED STAGE IV	0/6441 (0%)	0	1/6446 (0%)	1
LUNG NEOPLASM	2/6441 (0%)	2	4/6446 (0.1%)	4
LUNG NEOPLASM MALIGNANT	2/6441 (0%)	2	8/6446 (0.1%)	8
LUNG SQUAMOUS CELL CARCINOMA STAGE III	1/6441 (0%)	1	0/6446 (0%)	0
LYMPHOMA	1/6441 (0%)	1	0/6446 (0%)	0
MALIGNANT GLIOMA	1/6441 (0%)	1	0/6446 (0%)	0
MALIGNANT MELANOMA	1/6441 (0%)	1	3/6446 (0%)	4
MEDIASTINUM NEOPLASM	1/6441 (0%)	1	0/6446 (0%)	0
METASTASES TO BONE	0/6441 (0%)	0	1/6446 (0%)	1
METASTASES TO CENTRAL NERVOUS SYSTEM	2/6441 (0%)	2	1/6446 (0%)	1
METASTASES TO LARYNX	1/6441 (0%)	1	0/6446 (0%)	0
METASTASES TO LIVER	1/6441 (0%)	1	2/6446 (0%)	2
METASTASES TO LUNG	0/6441 (0%)	0	1/6446 (0%)	1
METASTASES TO LYMPH NODES	1/6441 (0%)	1	0/6446 (0%)	0
METASTATIC MALIGNANT MELANOMA	3/6441 (0%)	3	1/6446 (0%)	1
METASTATIC NEOPLASM	0/6441 (0%)	0	1/6446 (0%)	1
METASTATIC RENAL CELL CARCINOMA	0/6441 (0%)	0	1/6446 (0%)	1
METASTATIC SQUAMOUS CELL CARCINOMA	0/6441 (0%)	0	1/6446 (0%)	1
MYELODYSPLASTIC SYNDROME	2/6441 (0%)	2	0/6446 (0%)	0
NASAL CAVITY CANCER	0/6441 (0%)	0	1/6446 (0%)	1
NEOPLASM MALIGNANT	1/6441 (0%)	1	1/6446 (0%)	1
NEUROENDOCRINE CARCINOMA	1/6441 (0%)	1	0/6446 (0%)	0
NON-SMALL CELL LUNG CANCER	1/6441 (0%)	1	2/6446 (0%)	2
OESOPHAGEAL CARCINOMA	2/6441 (0%)	2	3/6446 (0%)	3
OESOPHAGEAL CARCINOMA RECURRENT	0/6441 (0%)	0	1/6446 (0%)	1
OVARIAN CANCER	2/6441 (0%)	2	1/6446 (0%)	1
OVARIAN CANCER METASTATIC	1/6441 (0%)	1	0/6446 (0%)	0
OVARIAN NEOPLASM	0/6441 (0%)	0	1/6446 (0%)	1
PAGET'S DISEASE OF SKIN	0/6441 (0%)	0	1/6446 (0%)	1
PANCREATIC CARCINOMA	2/6441 (0%)	2	3/6446 (0%)	3
PAPILLOMA	1/6441 (0%)	1	0/6446 (0%)	0
PHAEOCHROMOCYTOMA	4/6441 (0.1%)	4	0/6446 (0%)	0
PITUITARY TUMOUR BENIGN	1/6441 (0%)	1	0/6446 (0%)	0
PROSTATE CANCER	6/6441 (0.1%)	6	7/6446 (0.1%)	8
PROSTATE CANCER METASTATIC	0/6441 (0%)	0	2/6446 (0%)	2
PROSTATE CANCER RECURRENT	0/6441 (0%)	0	1/6446 (0%)	1
PROSTATIC ADENOMA	1/6441 (0%)	1	0/6446 (0%)	0
RECTAL ADENOMA	0/6441 (0%)	0	1/6446 (0%)	1
RECTAL CANCER	1/6441 (0%)	1	1/6446 (0%)	1
RECTAL NEOPLASM	1/6441 (0%)	1	0/6446 (0%)	0
RENAL CANCER	4/6441 (0.1%)	4	0/6446 (0%)	0
RENAL CANCER RECURRENT	1/6441 (0%)	1	0/6446 (0%)	0
RENAL CELL CARCINOMA	0/6441 (0%)	0	3/6446 (0%)	3
RENAL CELL CARCINOMA RECURRENT	0/6441 (0%)	0	1/6446 (0%)	1
RENAL NEOPLASM	3/6441 (0%)	3	1/6446 (0%)	1
RENAL ONCOCYTOMA	0/6441 (0%)	0	1/6446 (0%)	1
SARCOMA	0/6441 (0%)	0	1/6446 (0%)	1
SMALL CELL LUNG CANCER STAGE UNSPECIFIED	1/6441 (0%)	1	0/6446 (0%)	0
SMALL INTESTINE CARCINOMA	1/6441 (0%)	1	0/6446 (0%)	0
SQUAMOUS CELL CARCINOMA	2/6441 (0%)	2	2/6446 (0%)	2
SQUAMOUS CELL CARCINOMA OF SKIN	1/6441 (0%)	1	0/6446 (0%)	0
T-CELL LYMPHOMA	1/6441 (0%)	1	0/6446 (0%)	0
TESTIS CANCER	1/6441 (0%)	1	0/6446 (0%)	0
THYROID NEOPLASM	0/6441 (0%)	0	1/6446 (0%)	1
TONGUE NEOPLASM MALIGNANT STAGE UNSPECIFIED	1/6441 (0%)	1	1/6446 (0%)	1
TRANSITIONAL CELL CARCINOMA	3/6441 (0%)	3	1/6446 (0%)	1
UTERINE CANCER	0/6441 (0%)	0	1/6446 (0%)	1
Nervous system disorders
ALCOHOLIC SEIZURE	1/6441 (0%)	1	0/6446 (0%)	0
ATAXIA	2/6441 (0%)	2	1/6446 (0%)	1
BRACHIAL PLEXOPATHY	0/6441 (0%)	0	1/6446 (0%)	1
BRAIN MASS	0/6441 (0%)	0	1/6446 (0%)	1
BRAIN OEDEMA	0/6441 (0%)	0	1/6446 (0%)	1
CAROTID ARTERY DISEASE	1/6441 (0%)	1	2/6446 (0%)	2
CAROTID ARTERY OCCLUSION	1/6441 (0%)	1	1/6446 (0%)	1
CAROTID ARTERY STENOSIS	11/6441 (0.2%)	12	17/6446 (0.3%)	18
CARPAL TUNNEL SYNDROME	2/6441 (0%)	2	0/6446 (0%)	0
CEREBELLAR HAEMORRHAGE	1/6441 (0%)	1	0/6446 (0%)	0
CEREBRAL HAEMORRHAGE	1/6441 (0%)	1	4/6446 (0.1%)	4
CEREBRAL HYPOPERFUSION	0/6441 (0%)	0	1/6446 (0%)	1
CERVICOBRACHIAL SYNDROME	2/6441 (0%)	2	1/6446 (0%)	1
CLUSTER HEADACHE	1/6441 (0%)	1	0/6446 (0%)	0
COMA	1/6441 (0%)	1	0/6446 (0%)	0
CONVULSION	9/6441 (0.1%)	9	6/6446 (0.1%)	7
CRANIAL NERVE PARALYSIS	0/6441 (0%)	0	1/6446 (0%)	1
CRITICAL ILLNESS POLYNEUROPATHY	0/6441 (0%)	0	1/6446 (0%)	1
DEMENTIA	2/6441 (0%)	2	1/6446 (0%)	1
DEMENTIA ALZHEIMER'S TYPE	0/6441 (0%)	0	1/6446 (0%)	1
DEMENTIA WITH LEWY BODIES	0/6441 (0%)	0	1/6446 (0%)	1
DEPRESSED LEVEL OF CONSCIOUSNESS	1/6441 (0%)	1	0/6446 (0%)	0
DIABETIC NEUROPATHY	1/6441 (0%)	1	1/6446 (0%)	1
DIZZINESS	10/6441 (0.2%)	12	5/6446 (0.1%)	5
DYSAESTHESIA	0/6441 (0%)	0	1/6446 (0%)	1
DYSARTHRIA	3/6441 (0%)	3	0/6446 (0%)	0
ENCEPHALOPATHY	4/6441 (0.1%)	4	2/6446 (0%)	2
EPILEPSY	4/6441 (0.1%)	4	1/6446 (0%)	1
GRAND MAL CONVULSION	2/6441 (0%)	2	1/6446 (0%)	2
HAEMORRHAGE INTRACRANIAL	12/6441 (0.2%)	13	33/6446 (0.5%)	35
HAEMORRHAGIC STROKE	2/6441 (0%)	2	0/6446 (0%)	0
HAEMORRHAGIC TRANSFORMATION STROKE	0/6441 (0%)	0	2/6446 (0%)	2
HEADACHE	12/6441 (0.2%)	12	2/6446 (0%)	2
HEMIPARESIS	1/6441 (0%)	1	1/6446 (0%)	1
HEPATIC ENCEPHALOPATHY	0/6441 (0%)	0	1/6446 (0%)	1
HYPERTENSIVE ENCEPHALOPATHY	2/6441 (0%)	2	0/6446 (0%)	0
HYPOAESTHESIA	1/6441 (0%)	1	0/6446 (0%)	0
HYPOKINESIA	0/6441 (0%)	0	1/6446 (0%)	1
HYPOTONIA	0/6441 (0%)	0	1/6446 (0%)	1
HYPOXIC-ISCHAEMIC ENCEPHALOPATHY	1/6441 (0%)	1	1/6446 (0%)	1
INTERCOSTAL NEURALGIA	1/6441 (0%)	1	0/6446 (0%)	0
INTRACRANIAL ANEURYSM	1/6441 (0%)	1	0/6446 (0%)	0
LETHARGY	1/6441 (0%)	1	1/6446 (0%)	1
LOSS OF CONSCIOUSNESS	0/6441 (0%)	0	1/6446 (0%)	1
MENTAL IMPAIRMENT	0/6441 (0%)	0	1/6446 (0%)	1
MIGRAINE	1/6441 (0%)	1	0/6446 (0%)	0
MYASTHENIA GRAVIS	1/6441 (0%)	1	1/6446 (0%)	1
MYELOPATHY	0/6441 (0%)	0	1/6446 (0%)	1
NERVE COMPRESSION	0/6441 (0%)	0	2/6446 (0%)	2
NERVE DEGENERATION	0/6441 (0%)	0	1/6446 (0%)	1
NERVE ROOT COMPRESSION	1/6441 (0%)	1	0/6446 (0%)	0
NERVOUS SYSTEM DISORDER	1/6441 (0%)	1	0/6446 (0%)	0
NEURITIS	1/6441 (0%)	1	0/6446 (0%)	0
NEUROMYOPATHY	1/6441 (0%)	1	0/6446 (0%)	0
NEUROPATHY PERIPHERAL	2/6441 (0%)	2	1/6446 (0%)	1
NORMAL PRESSURE HYDROCEPHALUS	1/6441 (0%)	1	0/6446 (0%)	0
PARAESTHESIA	5/6441 (0.1%)	5	0/6446 (0%)	0
PARAPARESIS	1/6441 (0%)	1	0/6446 (0%)	0
PARKINSON'S DISEASE	1/6441 (0%)	1	1/6446 (0%)	1
PARTIAL SEIZURES	0/6441 (0%)	0	1/6446 (0%)	1
PERONEAL NERVE PALSY	0/6441 (0%)	0	1/6446 (0%)	1
PHRENIC NERVE PARALYSIS	0/6441 (0%)	0	1/6446 (0%)	1
PRESYNCOPE	7/6441 (0.1%)	7	4/6446 (0.1%)	4
PSYCHOMOTOR HYPERACTIVITY	1/6441 (0%)	1	0/6446 (0%)	0
SCIATICA	3/6441 (0%)	4	1/6446 (0%)	1
SEDATION	1/6441 (0%)	1	1/6446 (0%)	1
SENSORIMOTOR DISORDER	1/6441 (0%)	1	0/6446 (0%)	0
SENSORY LOSS	0/6441 (0%)	0	1/6446 (0%)	1
SPINAL CORD COMPRESSION	1/6441 (0%)	1	0/6446 (0%)	0
SPONDYLITIC MYELOPATHY	0/6441 (0%)	0	1/6446 (0%)	1
SUBARACHNOID HAEMORRHAGE	3/6441 (0%)	3	3/6446 (0%)	3
SUBDURAL HYGROMA	0/6441 (0%)	0	1/6446 (0%)	1
SYNCOPE	48/6441 (0.7%)	48	44/6446 (0.7%)	48
SYRINGOMYELIA	1/6441 (0%)	2	0/6446 (0%)	0
TREMOR	1/6441 (0%)	1	0/6446 (0%)	0
VASCULAR ENCEPHALOPATHY	0/6441 (0%)	0	2/6446 (0%)	2
VERTEBRAL ARTERY STENOSIS	0/6441 (0%)	0	1/6446 (0%)	1
VIITH NERVE PARALYSIS	1/6441 (0%)	1	1/6446 (0%)	1
Psychiatric disorders
ABNORMAL BEHAVIOUR	1/6441 (0%)	1	0/6446 (0%)	0
ADJUSTMENT DISORDER WITH MIXED DISTURBANCE OF EMOTION AND CONDUCT	0/6441 (0%)	0	1/6446 (0%)	1
AGITATION	1/6441 (0%)	1	0/6446 (0%)	0
ALCOHOL ABUSE	0/6441 (0%)	0	1/6446 (0%)	1
ALCOHOL WITHDRAWAL SYNDROME	0/6441 (0%)	0	2/6446 (0%)	2
ALCOHOLISM	1/6441 (0%)	1	0/6446 (0%)	0
ANXIETY	7/6441 (0.1%)	7	3/6446 (0%)	3
ANXIETY DISORDER	1/6441 (0%)	1	0/6446 (0%)	0
BIPOLAR I DISORDER	1/6441 (0%)	1	0/6446 (0%)	0
COMPLETED SUICIDE	2/6441 (0%)	2	1/6446 (0%)	1
CONFUSIONAL STATE	4/6441 (0.1%)	4	5/6446 (0.1%)	5
DELIRIUM	1/6441 (0%)	1	2/6446 (0%)	2
DEPRESSION	8/6441 (0.1%)	10	11/6446 (0.2%)	15
HALLUCINATION	1/6441 (0%)	1	0/6446 (0%)	0
HALLUCINATION, VISUAL	1/6441 (0%)	1	0/6446 (0%)	0
MAJOR DEPRESSION	2/6441 (0%)	2	1/6446 (0%)	2
MENTAL STATUS CHANGES	3/6441 (0%)	3	2/6446 (0%)	2
PANIC ATTACK	1/6441 (0%)	1	0/6446 (0%)	0
PSYCHOTIC DISORDER	1/6441 (0%)	1	1/6446 (0%)	1
SCHIZOAFFECTIVE DISORDER BIPOLAR TYPE	1/6441 (0%)	1	0/6446 (0%)	0
SUBSTANCE ABUSE	0/6441 (0%)	0	1/6446 (0%)	1
SUICIDAL IDEATION	2/6441 (0%)	2	3/6446 (0%)	3
SUICIDE ATTEMPT	1/6441 (0%)	1	3/6446 (0%)	3
TOBACCO WITHDRAWAL SYMPTOMS	0/6441 (0%)	0	1/6446 (0%)	1
Renal and urinary disorders
BLADDER DYSFUNCTION	1/6441 (0%)	1	0/6446 (0%)	0
CALCULUS BLADDER	1/6441 (0%)	1	1/6446 (0%)	1
CALCULUS URETERIC	1/6441 (0%)	1	4/6446 (0.1%)	4
CALCULUS URINARY	2/6441 (0%)	2	2/6446 (0%)	2
HAEMATURIA	15/6441 (0.2%)	16	31/6446 (0.5%)	37
HAEMORRHAGE URINARY TRACT	2/6441 (0%)	2	5/6446 (0.1%)	6
HYDRONEPHROSIS	0/6441 (0%)	0	1/6446 (0%)	1
NEPHROLITHIASIS	6/6441 (0.1%)	6	7/6446 (0.1%)	7
NEPHROPATHY	1/6441 (0%)	1	1/6446 (0%)	1
NEPHROPATHY TOXIC	3/6441 (0%)	3	1/6446 (0%)	1
NEPHROTIC SYNDROME	1/6441 (0%)	1	3/6446 (0%)	3
NEUROGENIC BLADDER	1/6441 (0%)	2	0/6446 (0%)	0
OBSTRUCTIVE UROPATHY	0/6441 (0%)	0	2/6446 (0%)	2
POLYURIA	1/6441 (0%)	1	0/6446 (0%)	0
RENAL ANEURYSM	1/6441 (0%)	1	0/6446 (0%)	0
RENAL ARTERY OCCLUSION	1/6441 (0%)	1	0/6446 (0%)	0
RENAL ARTERY STENOSIS	3/6441 (0%)	4	2/6446 (0%)	2
RENAL COLIC	4/6441 (0.1%)	5	6/6446 (0.1%)	6
RENAL CYST	1/6441 (0%)	1	0/6446 (0%)	0
RENAL DISORDER	0/6441 (0%)	0	1/6446 (0%)	1
RENAL FAILURE	50/6441 (0.8%)	55	56/6446 (0.9%)	61
RENAL FAILURE ACUTE	36/6441 (0.6%)	38	38/6446 (0.6%)	39
RENAL FAILURE CHRONIC	5/6441 (0.1%)	5	8/6446 (0.1%)	9
RENAL IMPAIRMENT	1/6441 (0%)	1	2/6446 (0%)	2
RENAL MASS	1/6441 (0%)	1	0/6446 (0%)	0
RENAL TUBULAR NECROSIS	1/6441 (0%)	1	1/6446 (0%)	1
STRESS URINARY INCONTINENCE	0/6441 (0%)	0	1/6446 (0%)	1
TUBULOINTERSTITIAL NEPHRITIS	0/6441 (0%)	0	1/6446 (0%)	1
URINARY RETENTION	4/6441 (0.1%)	4	6/6446 (0.1%)	6
URINARY TRACT OBSTRUCTION	0/6441 (0%)	0	1/6446 (0%)	1
Reproductive system and breast disorders
BENIGN PROSTATIC HYPERPLASIA	4/6441 (0.1%)	4	9/6446 (0.1%)	9
BREAST INFLAMMATION	1/6441 (0%)	1	0/6446 (0%)	0
CYSTOCELE	1/6441 (0%)	1	0/6446 (0%)	0
EPIDIDYMITIS	1/6441 (0%)	1	1/6446 (0%)	1
GENITAL HAEMORRHAGE	1/6441 (0%)	1	1/6446 (0%)	1
OVARIAN CYST	0/6441 (0%)	0	1/6446 (0%)	1
PELVIC FLUID COLLECTION	0/6441 (0%)	0	1/6446 (0%)	1
POSTMENOPAUSAL HAEMORRHAGE	0/6441 (0%)	0	2/6446 (0%)	2
PROSTATITIS	2/6441 (0%)	2	2/6446 (0%)	3
PROSTATOMEGALY	0/6441 (0%)	0	1/6446 (0%)	1
RECTOCELE	0/6441 (0%)	0	1/6446 (0%)	1
UTERINE ENLARGEMENT	0/6441 (0%)	0	1/6446 (0%)	1
UTERINE PROLAPSE	1/6441 (0%)	1	0/6446 (0%)	0
VAGINAL PROLAPSE	0/6441 (0%)	0	1/6446 (0%)	1
Respiratory, thoracic and mediastinal disorders
ACUTE PULMONARY OEDEMA	9/6441 (0.1%)	9	14/6446 (0.2%)	14
ACUTE RESPIRATORY DISTRESS SYNDROME	4/6441 (0.1%)	4	4/6446 (0.1%)	4
ACUTE RESPIRATORY FAILURE	16/6441 (0.2%)	16	15/6446 (0.2%)	16
ALLERGIC GRANULOMATOUS ANGIITIS	0/6441 (0%)	0	1/6446 (0%)	1
ALVEOLITIS ALLERGIC	1/6441 (0%)	1	0/6446 (0%)	0
APNOEA	1/6441 (0%)	1	0/6446 (0%)	0
ASPIRATION	0/6441 (0%)	0	1/6446 (0%)	1
ASTHMA	5/6441 (0.1%)	6	3/6446 (0%)	3
ATELECTASIS	6/6441 (0.1%)	6	2/6446 (0%)	2
BRONCHIAL HYPERREACTIVITY	1/6441 (0%)	1	1/6446 (0%)	1
BRONCHIAL OBSTRUCTION	1/6441 (0%)	1	0/6446 (0%)	0
BRONCHITIS CHRONIC	3/6441 (0%)	3	2/6446 (0%)	2
BRONCHOSPASM	1/6441 (0%)	1	2/6446 (0%)	2
CHRONIC OBSTRUCTIVE PULMONARY DISEASE	51/6441 (0.8%)	71	44/6446 (0.7%)	68
CHYLOTHORAX	1/6441 (0%)	1	0/6446 (0%)	0
COUGH	0/6441 (0%)	0	2/6446 (0%)	2
DIAPHRAGMATIC HERNIA	1/6441 (0%)	1	0/6446 (0%)	0
DIAPHRAGMATIC PARALYSIS	1/6441 (0%)	1	1/6446 (0%)	1
DYSPNOEA	20/6441 (0.3%)	20	20/6446 (0.3%)	22
DYSPNOEA EXERTIONAL	0/6441 (0%)	0	2/6446 (0%)	2
DYSPNOEA PAROXYSMAL NOCTURNAL	0/6441 (0%)	0	1/6446 (0%)	1
EPISTAXIS	9/6441 (0.1%)	9	21/6446 (0.3%)	22
HAEMOPTYSIS	7/6441 (0.1%)	8	7/6446 (0.1%)	7
HAEMOTHORAX	7/6441 (0.1%)	7	3/6446 (0%)	3
HICCUPS	1/6441 (0%)	1	0/6446 (0%)	0
HYDROTHORAX	0/6441 (0%)	0	1/6446 (0%)	1
HYPERVENTILATION	1/6441 (0%)	1	0/6446 (0%)	0
INTERSTITIAL LUNG DISEASE	2/6441 (0%)	3	0/6446 (0%)	0
LARYNGEAL OEDEMA	1/6441 (0%)	1	0/6446 (0%)	0
LARYNGEAL STENOSIS	0/6441 (0%)	0	1/6446 (0%)	1
LUNG DISORDER	0/6441 (0%)	0	1/6446 (0%)	1
LUNG INFILTRATION	1/6441 (0%)	1	0/6446 (0%)	0
NASAL POLYPS	0/6441 (0%)	0	1/6446 (0%)	1
OBSTRUCTIVE AIRWAYS DISORDER	1/6441 (0%)	1	1/6446 (0%)	1
OROPHARYNGEAL SWELLING	0/6441 (0%)	0	1/6446 (0%)	1
PHARYNGEAL HAEMORRHAGE	2/6441 (0%)	2	0/6446 (0%)	0
PLEURAL EFFUSION	30/6441 (0.5%)	31	32/6446 (0.5%)	38
PLEURAL HAEMORRHAGE	1/6441 (0%)	1	0/6446 (0%)	0
PLEURISY	0/6441 (0%)	0	1/6446 (0%)	1
PLEURITIC PAIN	1/6441 (0%)	1	2/6446 (0%)	2
PNEUMONIA ASPIRATION	6/6441 (0.1%)	7	4/6446 (0.1%)	4
PNEUMONITIS	1/6441 (0%)	1	1/6446 (0%)	1
PNEUMOTHORAX	3/6441 (0%)	3	4/6446 (0.1%)	4
PULMONARY ALVEOLAR HAEMORRHAGE	1/6441 (0%)	1	1/6446 (0%)	1
PULMONARY CONGESTION	4/6441 (0.1%)	4	4/6446 (0.1%)	4
PULMONARY EMBOLISM	34/6441 (0.5%)	34	20/6446 (0.3%)	20
PULMONARY EOSINOPHILIA	0/6441 (0%)	0	1/6446 (0%)	1
PULMONARY FIBROSIS	1/6441 (0%)	1	1/6446 (0%)	1
PULMONARY HAEMORRHAGE	0/6441 (0%)	0	2/6446 (0%)	2
PULMONARY HYPERTENSION	1/6441 (0%)	1	0/6446 (0%)	0
PULMONARY MASS	0/6441 (0%)	0	2/6446 (0%)	2
PULMONARY OEDEMA	12/6441 (0.2%)	13	19/6446 (0.3%)	23
RESPIRATORY ARREST	2/6441 (0%)	2	4/6446 (0.1%)	4
RESPIRATORY DISTRESS	2/6441 (0%)	2	5/6446 (0.1%)	5
RESPIRATORY FAILURE	26/6441 (0.4%)	27	30/6446 (0.5%)	30
RESPIRATORY TRACT INFLAMMATION	1/6441 (0%)	1	0/6446 (0%)	0
RESTRICTIVE PULMONARY DISEASE	1/6441 (0%)	1	0/6446 (0%)	0
SLEEP APNOEA SYNDROME	2/6441 (0%)	2	2/6446 (0%)	2
TONSILLAR HYPERTROPHY	0/6441 (0%)	0	1/6446 (0%)	1
VOCAL CORD POLYP	0/6441 (0%)	0	1/6446 (0%)	2
Skin and subcutaneous tissue disorders
ANGIOEDEMA	2/6441 (0%)	2	1/6446 (0%)	1
DECUBITUS ULCER	0/6441 (0%)	0	1/6446 (0%)	1
DERMATITIS	0/6441 (0%)	0	1/6446 (0%)	1
DERMATITIS EXFOLIATIVE	1/6441 (0%)	1	0/6446 (0%)	0
DIABETIC ULCER	1/6441 (0%)	1	0/6446 (0%)	0
DRUG ERUPTION	1/6441 (0%)	1	1/6446 (0%)	1
DYSHIDROSIS	0/6441 (0%)	0	1/6446 (0%)	1
HYPERHIDROSIS	0/6441 (0%)	0	1/6446 (0%)	1
NEUROPATHIC ULCER	1/6441 (0%)	1	0/6446 (0%)	0
PEMPHIGOID	0/6441 (0%)	0	1/6446 (0%)	1
PEMPHIGUS	1/6441 (0%)	1	0/6446 (0%)	0
PSORIASIS	3/6441 (0%)	3	0/6446 (0%)	0
PURPURA	0/6441 (0%)	0	1/6446 (0%)	1
RASH	3/6441 (0%)	3	2/6446 (0%)	2
RASH MACULO-PAPULAR	1/6441 (0%)	1	0/6446 (0%)	0
SKIN EXFOLIATION	1/6441 (0%)	1	0/6446 (0%)	0
SKIN HAEMORRHAGE	1/6441 (0%)	1	0/6446 (0%)	0
SKIN LESION	0/6441 (0%)	0	1/6446 (0%)	1
SKIN NECROSIS	0/6441 (0%)	0	2/6446 (0%)	2
SKIN ULCER	1/6441 (0%)	1	3/6446 (0%)	3
STASIS DERMATITIS	1/6441 (0%)	1	0/6446 (0%)	0
SUBCUTANEOUS EMPHYSEMA	1/6441 (0%)	1	1/6446 (0%)	1
URTICARIA	1/6441 (0%)	1	1/6446 (0%)	1
Surgical and medical procedures
CARDIAC OPERATION	2/6441 (0%)	2	1/6446 (0%)	1
CATARACT OPERATION	1/6441 (0%)	1	1/6446 (0%)	1
DIABETES MELLITUS MANAGEMENT	1/6441 (0%)	1	0/6446 (0%)	0
WOUND DRAINAGE	1/6441 (0%)	1	0/6446 (0%)	0
Vascular disorders
ACCELERATED HYPERTENSION	2/6441 (0%)	2	0/6446 (0%)	0
ANEURYSM	0/6441 (0%)	0	1/6446 (0%)	1
AORTIC ANEURYSM	5/6441 (0.1%)	5	6/6446 (0.1%)	7
AORTIC ANEURYSM RUPTURE	0/6441 (0%)	0	1/6446 (0%)	1
AORTIC DISSECTION	6/6441 (0.1%)	6	2/6446 (0%)	2
AORTIC DISSECTION RUPTURE	0/6441 (0%)	0	1/6446 (0%)	1
AORTIC RUPTURE	1/6441 (0%)	1	0/6446 (0%)	0
AORTIC STENOSIS	4/6441 (0.1%)	4	4/6446 (0.1%)	4
AORTIC THROMBOSIS	1/6441 (0%)	1	0/6446 (0%)	0
ARTERIAL OCCLUSIVE DISEASE	4/6441 (0.1%)	4	0/6446 (0%)	0
ARTERIAL STENOSIS LIMB	1/6441 (0%)	1	0/6446 (0%)	0
ARTERIAL THROMBOSIS LIMB	0/6441 (0%)	0	2/6446 (0%)	3
ARTERIOSCLEROSIS OBLITERANS	2/6441 (0%)	2	1/6446 (0%)	1
ARTERIOVENOUS FISTULA	0/6441 (0%)	0	1/6446 (0%)	1
CIRCULATORY COLLAPSE	2/6441 (0%)	2	0/6446 (0%)	0
COELIAC ARTERY OCCLUSION	1/6441 (0%)	1	0/6446 (0%)	0
DEEP VEIN THROMBOSIS	10/6441 (0.2%)	10	13/6446 (0.2%)	13
DIABETIC MACROANGIOPATHY	1/6441 (0%)	1	0/6446 (0%)	0
EMBOLISM	1/6441 (0%)	1	0/6446 (0%)	0
ESSENTIAL HYPERTENSION	2/6441 (0%)	2	0/6446 (0%)	0
FEMORAL ARTERIAL STENOSIS	2/6441 (0%)	2	1/6446 (0%)	1
FEMORAL ARTERY ANEURYSM	1/6441 (0%)	1	0/6446 (0%)	0
FEMORAL ARTERY DISSECTION	0/6441 (0%)	0	1/6446 (0%)	1
FEMORAL ARTERY OCCLUSION	3/6441 (0%)	3	0/6446 (0%)	0
HAEMATOMA	7/6441 (0.1%)	7	20/6446 (0.3%)	26
HAEMODYNAMIC INSTABILITY	2/6441 (0%)	2	1/6446 (0%)	1
HAEMORRHAGE	12/6441 (0.2%)	12	13/6446 (0.2%)	13
HYPERTENSION	23/6441 (0.4%)	25	22/6446 (0.3%)	24
HYPERTENSIVE CRISIS	13/6441 (0.2%)	13	20/6446 (0.3%)	21
HYPERTENSIVE EMERGENCY	2/6441 (0%)	2	1/6446 (0%)	1
HYPOTENSION	28/6441 (0.4%)	29	29/6446 (0.4%)	29
HYPOVOLAEMIC SHOCK	2/6441 (0%)	2	0/6446 (0%)	0
ILIAC ARTERY STENOSIS	2/6441 (0%)	2	3/6446 (0%)	3
INTERMITTENT CLAUDICATION	14/6441 (0.2%)	16	9/6446 (0.1%)	9
INTRA-ABDOMINAL HAEMATOMA	0/6441 (0%)	0	1/6446 (0%)	1
JUGULAR VEIN THROMBOSIS	0/6441 (0%)	0	1/6446 (0%)	1
LABILE HYPERTENSION	1/6441 (0%)	1	0/6446 (0%)	0
LERICHE SYNDROME	1/6441 (0%)	1	1/6446 (0%)	1
MALIGNANT HYPERTENSION	1/6441 (0%)	1	0/6446 (0%)	0
ORTHOSTATIC HYPOTENSION	10/6441 (0.2%)	10	6/6446 (0.1%)	6
PELVIC VENOUS THROMBOSIS	1/6441 (0%)	1	0/6446 (0%)	0
PERIPHERAL ARTERIAL OCCLUSIVE DISEASE	11/6441 (0.2%)	12	13/6446 (0.2%)	14
PERIPHERAL ARTERY ANEURYSM	2/6441 (0%)	2	0/6446 (0%)	0
PERIPHERAL ARTERY DISSECTION	0/6441 (0%)	0	1/6446 (0%)	1
PERIPHERAL EMBOLISM	0/6441 (0%)	0	1/6446 (0%)	1
PERIPHERAL ISCHAEMIA	9/6441 (0.1%)	10	7/6446 (0.1%)	7
PERIPHERAL VASCULAR DISORDER	5/6441 (0.1%)	7	8/6446 (0.1%)	9
PHLEBITIS	0/6441 (0%)	0	2/6446 (0%)	2
POOR PERIPHERAL CIRCULATION	1/6441 (0%)	1	0/6446 (0%)	0
SHOCK	1/6441 (0%)	1	3/6446 (0%)	3
SHOCK HAEMORRHAGIC	0/6441 (0%)	0	1/6446 (0%)	1
SUBCLAVIAN ARTERY STENOSIS	2/6441 (0%)	2	1/6446 (0%)	1
SUBCLAVIAN STEAL SYNDROME	1/6441 (0%)	1	0/6446 (0%)	0
TEMPORAL ARTERITIS	0/6441 (0%)	0	1/6446 (0%)	2
THROMBOANGIITIS OBLITERANS	1/6441 (0%)	1	0/6446 (0%)	0
THROMBOPHLEBITIS	0/6441 (0%)	0	2/6446 (0%)	2
THROMBOPHLEBITIS SUPERFICIAL	1/6441 (0%)	1	0/6446 (0%)	0
VARICOSE VEIN	0/6441 (0%)	0	2/6446 (0%)	2
VASCULAR INSUFFICIENCY	0/6441 (0%)	0	1/6446 (0%)	1
VASCULAR STENOSIS	1/6441 (0%)	1	0/6446 (0%)	0
VASCULITIS	1/6441 (0%)	1	0/6446 (0%)	0
VASODILATATION	0/6441 (0%)	0	1/6446 (0%)	1
VENA CAVA THROMBOSIS	1/6441 (0%)	1	0/6446 (0%)	0
VENOUS THROMBOSIS	1/6441 (0%)	1	1/6446 (0%)	1
VENOUS THROMBOSIS LIMB	0/6441 (0%)	0	1/6446 (0%)	1
Other (Not Including Serious) Adverse Events
	Placebo		Vorapaxar
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	832/6441 (12.9%)		1081/6446 (16.8%)
Nervous system disorders
HEADACHE	385/6441 (6%)	424	398/6446 (6.2%)	451
Respiratory, thoracic and mediastinal disorders
EPISTAXIS	228/6441 (3.5%)	293	432/6446 (6.7%)	552
Vascular disorders
HYPERTENSION	310/6441 (4.8%)	359	368/6446 (5.7%)	399

Limitations/Caveats

Prior to the planned study completion, the Data Safety Monitoring Board recommended that all participants stop treatment and that the study be closed-out. The protocol-defined target number of primary efficacy endpoints had been reached by this time.

More Information

Certain Agreements

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

All draft publications will be submitted to the Publication Committee for review. Full-length papers will be submitted at least 45 days prior to submission to a journal. Abstracts or public presentations (eg, poster) will be submitted at least 14 days in advance.