Irbesartan in Heart Failure With Preserved Systolic Function (I-Preserve)

• Sponsor: Bristol-Myers Squibb (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00095238
• Collaborator: Sanofi (Industry)
• Enrollment: 4,128
• Locations: 231
• Arms: 2
• Duration (Months): 73
• Patients Per Site: 17.9
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this clinical research study is to learn if Irbesartan is superior to placebo in reducing mortality and cardiovascular morbidity in subjects with heart failure with preserved systolic function. The safety of this treatment will also be studied.

Condition or Disease	Intervention/Treatment	Phase
Congestive Heart Failure	Drug: Irbesartan; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 4128 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Irbesartan in Heart Failure With Preserved Systolic Function (I-Preserve)
• Study Start Date: Jun 1, 2002
• Actual Primary Completion Date: Jul 1, 2008
• Actual Study Completion Date: Jul 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 1	Drug: Irbesartan; Tablets, Oral, titration from 75 to 300 mg, once daily up to 6 years
Placebo Comparator: 2	Drug: Placebo; Tablets, Oral, titration from 75 to 300 mg, once daily up to 6 years

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With First Occurrence of the Composite Outcome of Death (All Cause) or Protocol-Specified Cardiovascular (CV) Hospitalization at Given Timepoints [Year 1, Year 2, Year 3, Year 4, Year 5]

   Treatment comparisons for time to first occurrence of composite outcome of all-cause death (composite outcome of death) or protocol-specified CV hospitalization. Protocol-specified CV hospitalizations include those ≥24 hrs or involving a calendar date change for a primary cause of worsening heart failure, unstable angina, myocardial infarction, ventricular or atrial dysrhythmia, or stroke, that also require intravenous or intramuscular therapy or a related procedure or significant augmentation of oral therapy. In addition, MI or stroke during any hospitalization are included.

Secondary Outcome Measures

1. Percentage of Participants Experiencing Heart Failure Mortality or Heart Failure Hospitalization at Given Time Points [Year 1, Year 2, Year 3, Year 4, Year 5]

   Treatment comparisons for time to heart failure mortality or heart failure hospitalization

2. Minnesota Living With Heart Failure (MLwHF) Total Score (Sum of Questions 1-21) at Month 6 and Month 14 [Baseline, Month 6, Month 14]

   Mean score and adjusted mean change from baseline in Minnesota Living with Heart Failure (MLWHF) questionnaire, a 21-item, patient-reported, 6-point (ranging from 0-5; higher score=poorer quality of life; highest possible score=105) measurement of quality of life in persons with heart failure.

3. Minnesota Living With Heart Failure (MLwHF) Total Score (Sum of Questions 1-21) at Final Visit [Baseline, Final Visit=last scheduled visit specified in the protocol at conclusion of the entire study by the sponsor. The trial was designed to end after 1440 primary endpoint events, projected duration=6.0 ± 0.5 years.]

   Mean score at baseline and final visit in Minnesota Living with Heart Failure (MLWHF) questionnaire, a 21-item, patient-reported, 6-point (ranging from 0-5; higher score=poorer quality of life; highest possible score=105) measurement of quality of life in persons with heart failure.

4. Change From Baseline in B-Type Natriuretic Peptide (Pro-BNP) at Month 6 and Month 14 [Baseline, Month 6, Month 14]

   Adjusted ratio to baseline in geometric mean in Pro-BNP in the blood. Ratio to Baseline = On-therapy geometric mean divided by baseline geometric mean. A lower score signifies improvement. Change from baseline adjusted for baseline value and angiotensin converting enzyme inhibitor use at baseline. Analysis uses natural logarithms of excretion rate values.

5. Percentage of Participants Experiencing CV Death, Non-Fatal Myocardial Infarction (MI), or Non-Fatal Stroke at Given Timepoints [Year 1, Year 2, Year 3, Year 4, Year 5]

   Treatment comparisons for time to cardiovascular death, non-fatal MI, or non-fatal stroke.

6. Percentage of Participants Experiencing Cardiovascular Death at Given Timepoints [Year 1, Year 2, Year 3, Year 4, Year 5]

   Treatment comparisons for time to cardiovascular death

7. Percentage of Participants Experiencing All-cause Death at Given Time Points [Year 1, Year 2, Year 3, Year 4, Year 5]

   Treatment comparisons for time to all-cause death

8. Change From Baseline in the New York Heart Association (NYHA) Functional Class at Month 6, Month 10, Month 14, and Final Visit [Baseline, Month 6, Month 10, Month 14, Final Visit. The trial was designed to end after 1440 primary endpoint events, projected duration=6.0 ± 0.5 years.]

   NYHA functional classification=4-tiered system relating symptoms to everyday activities & quality of life. (See Reporting Groups for description of each class.) Change of NYHA functional class from baseline was grouped into 3 categories: improved, unchanged, or worsened (based on case report form [CRF] assessment). If a post-randomization CRF assessment was missing or participant died, was hospitalized for worsening heart failure or discontinued study medication for worsening heart failure, the participant was classified as Major Event.

9. Physician Assessment of Heart Failure Status at Month 6, Month 14, and Final Visit Compared With Baseline [Baseline, Month 6, Month 14, Final Visit. The trial was designed to end after 1440 primary endpoint events, projected duration=6.0 ± 0.5 years.]

   This was an assessment of the change in overall physician opinion of change from baseline status. Assessments are directly based on the Case Report Form (CRF). If the post-randomization CRF assessment was missing and the subject died, was hospitalized for worsening heart failure, or discontinued study medication for worsening heart failure, the subject was considered as having a Major Event. Participants who are summarized under Major Events are categorized as Worsened Markedly.

10. Participant Assessment of Heart Failure Status at Month 6, Month 14, and Final Visit Compared With Baseline [Baseline, Month 6, Month 14, Final Visit. The trial was designed to end after 1440 primary endpoint events, projected duration=6.0 ± 0.5 years.]

    Assessments are directly based on the Case Report Form (CRF). If the post-randomization CRF assessment was missing and the subject died, was hospitalized for worsening heart failure, or discontinued study medication for worsening heart failure, the subject was considered as having a Major Event. Participants who are summarized under Major Events are categorized as Worsened Markedly.

11. Participant Assessment of Fatigue at Month 6, Month 14, and Final Visit Compared With Baseline [Baseline, Month 6, Month 14, Final Visit. The trial was designed to end after 1440 primary endpoint events, projected duration=6.0 ± 0.5 years.]

    Assessments are directly based on the Case Report Form (CRF). If the post-randomization CRF assessment was missing and the subject died, was hospitalized for worsening heart failure, or discontinued study medication for worsening heart failure, the subject was considered as having a Major Event. Participants who are summarized under Major Events are categorized as Worsened Markedly.

12. Participant Assessment of Dyspnea at Month 6, Month 14, and Final Visit Compared With Baseline [Baseline, Month 6, Month 14, Final Visit. The trial was designed to end after 1440 primary endpoint events, projected duration=6.0 ± 0.5 years.]

    Assessments are directly based on the Case Report Form (CRF). If the post-randomization CRF assessment was missing and the subject died, was hospitalized for worsening heart failure, or discontinued study medication for worsening heart failure, the subject was considered as having a Major Event. Participants who are summarized under Major Events are categorized as Worsened Markedly.

13. Percentage of Participants Experiencing CV Death or CV Hospitalization at Given Timepoints [Year 1, Year 2, Year 3, Year 4, Year 5]

    Treatment comparisons for time to CV death or CV hospitalization. Protocol-specified CV hospitalizations include hospitalizations ≥24 hrs or involve a calendar date change for a primary cause of worsening heart failure, unstable angina, myocardial infarction, ventricular dysrhythmia, atrial dysrhythmia or stroke that also requires intravenous or intramuscular therapy or a related procedure or significant augmentation of oral therapy. Protocol specified CV hospitalizations also include myocardial infarction or stroke occurring during any hospitalization.

14. Percentage of Participants Experiencing Protocol-specified Cardiovascular (CV) Hospitalization at Given Timepoints [Year 1, Year 2, Year 3, Year 4, Year 5]

    Treatment comparisons for time to protocol-specified CV hospitalization. Protocol-specified CV hospitalizations include hospitalizations ≥24 hrs or involve a calendar date change for a primary cause of worsening heart failure, unstable angina, myocardial infarction, ventricular dysrhythmia, atrial dysrhythmia or stroke that also requires intravenous or intramuscular therapy or a related procedure or significant augmentation of oral therapy. Protocol specified CV hospitalizations also include myocardial infarction or stroke occurring during any hospitalization.

15. Percentage of Participants With New Onset of Diabetes Among Subjects With No Prior Diabetes History at Given Timepoints [Year 1, Year 2, Year 3, Year 4, Year 5]

    Treatment comparisons for time to new onset of diabetes (from adverse event reporting) among subjects with no prior history of diabetes.

16. Mean Change From Baseline in Glomerular Filtration Rate (GFR) at Month 6, Month 18, and Month 30 [Baseline, Month 6, Month 18, Month 30]

    Based on the Cockcroft-Gault formula calculation, a commonly used surrogate marker to estimate creatinine clearance, which in turn is an approximate measure of GFR. It employs serum creatinine measurements and a patient's weight to predict the creatinine clearance. Adjusted for baseline GFR and angiotensin-converting enzyme inhibitor use at baseline (ACE-I). A decrease from baseline signifies worsening. The adjusted mean change from baseline value is from the model (calculated prior to rounding), whereas the other two points are the baseline mean and post mean.

17. Mean Change From Baseline in Glomerular Filtration Rate (GFR)at Month 42, Month 54, Month 66 [Baseline, Month 42, Month 54, Month 66]

    Based on the Cockcroft-Gault formula calculation, a commonly used surrogate marker to estimate creatinine clearance, which in turn is an approximate measure of GFR. It employs serum creatinine measurements and a patient's weight to predict the creatinine clearance. Adjusted for baseline GFR and angiotensin-converting enzyme inhibitor use at baseline (ACE-I). A decrease from baseline signifies worsening. The adjusted mean change from baseline value is from the model (calculated prior to rounding), whereas the other two points are the baseline mean and post mean.

18. Number of Participants With New Onset Atrial Fibrillation (AF) Among Those With No Prior AF History or Evidence of AF on Baseline Electrocardiograph (ECG) [Baseline, Final Visit]

    Frequency of new onset AF in participants with no prior AF history or evidence of AF on baseline ECG. Stratified by use of angiotensin-converting enzyme (ACE) inhibitors and measured by adverse events reporting and final ECG recording read by the investigator.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 60 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male or female age >= 60 years with current symptoms of heart failure consistent with New York Heart Association (NYHA) class II-IV

• Left ventricular ejection fraction (LVEF) > = 45%

• Willing to provide written informed consent AND hospitalization for heart failure within the past 6 months OR various abnormalities in electrocardiogram, echocardiogram or chest x-ray indicating heart disease.

Exclusion Criteria:

• Acute myocardial infarction within 3 months;

• Heart revascularization procedure within 3 months;

• Hospitalization for angina within 3 months;

• Other heart surgery

• Life-threatening or uncontrolled arrhythmia

• Subjects with an implantable cardioverter-defibrillator that has discharged in the past 3 months;

• Stroke or surgery of the arteries in the brain within 3 months;

• Serious lung disease which requires use of home oxygen.

• Significantly low blood pressure

• Significantly high blood pressure

• Other known diseases that may limit life expectancy to <3 years;

• Known or suspected bilateral kidney artery narrowing;

• Geographic or social factors making study participation and follow-up impractical.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Local Institution	Birmingham	Alabama	United States
2	Local Institution	Peoria	Arizona	United States
3	Local Institution	Tucson	Arizona	United States
4	Local Institution	Little Rock	Arkansas	United States
5	Local Institution	Los Angeles	California	United States
6	Local Institution	San Diego	California	United States
7	Local Institution	San Francisco	California	United States
8	Local Institution	Farmington	Connecticut	United States
9	Local Institution	Jacksonville Beach	Florida	United States
10	Local Institution	Jacksonville	Florida	United States
11	Local Institution	Lake Worth	Florida	United States
12	Local Institution	Tampa	Florida	United States
13	Local Institution	Vero Beach	Florida	United States
14	Local Institution	Chicago	Illinois	United States
15	Local Institution	Peoria	Illinois	United States
16	Local Institution	Jeffersonville	Indiana	United States
17	Local Institution	Louisville	Kentucky	United States
18	Local Institution	Chalmette	Louisiana	United States
19	Local Institution	Shreveport	Louisiana	United States
20	Local Institution	Auburn	Maine	United States
21	Local Institution	Takoma Park	Maryland	United States
22	Local Institution	Towson	Maryland	United States
23	Local Institution	Boston	Massachusetts	United States
24	Local Institution	Haverhill	Massachusetts	United States
25	Local Institution	Natick	Massachusetts	United States
26	Local Institution	Detroit	Michigan	United States
27	Local Institution	Petoskey	Michigan	United States
28	Local Institution	Minneapolis	Minnesota	United States
29	Local Institution	St. Louis	Missouri	United States
30	Local Institution	Omaha	Nebraska	United States
31	Local Institution	Reno	Nevada	United States
32	Local Institution	Lebanon	New Hampshire	United States
33	Local Institution	Elmer	New Jersey	United States
34	Local Institution	Albuquerque	New Mexico	United States
35	Local Institution	Albany	New York	United States
36	Local Institution	Bronx	New York	United States
37	Local Institution	East Syracuse	New York	United States
38	Local Institution	Flushing	New York	United States
39	Local Institution	Rochester	New York	United States
40	Local Institution	Troy	New York	United States
41	Local Institution	Chapel Hill	North Carolina	United States
42	Local Institution	Concord	North Carolina	United States
43	Local Institution	Durham	North Carolina	United States
44	Local Institution	Winston-Salem	North Carolina	United States
45	Local Institution	Canton	Ohio	United States
46	Local Institution	Cincinnati	Ohio	United States
47	Local Institution	Columbus	Ohio	United States
48	Local Institution	Lorain	Ohio	United States
49	Local Institution	Sandusky	Ohio	United States
50	Local Institution	Portland	Oregon	United States
51	Local Institution	Flourtown	Pennsylvania	United States
52	Local Institution	Lancaster	Pennsylvania	United States
53	Local Institution	Charleston	South Carolina	United States
54	Local Institution	Germantown	Tennessee	United States
55	Local Institution	Austin	Texas	United States
56	Local Institution	Lynchberg	Virginia	United States
57	Local Institution	Richmond	Virginia	United States
58	Local Institution	South Boston	Virginia	United States
59	Local Institution	Spokane	Washington	United States
60	Local Institution	Madison	Wisconsin	United States
61	Local Institution	San Martin	Buenos Aires	Argentina
62	Local Institution	Rosario	Santa Fe	Argentina
63	Local Institution	Buenos Aires		Argentina
64	Local Institution	Cordoba		Argentina
65	Local Institution	Corrientes		Argentina
66	Local Institution	Mendoza		Argentina
67	Local Institution	Coffs Harbour	New South Wales	Australia
68	Local Institution	Concord	New South Wales	Australia
69	Local Institution	Garran	New South Wales	Australia
70	Local Institution	Kogarah	New South Wales	Australia
71	Local Institution	Randwick	New South Wales	Australia
72	Local Institution	Auchenflower	Queensland	Australia
73	Local Institution	Brisbane	Queensland	Australia
74	Local Institution	Woolloongabba	Queensland	Australia
75	Local Institution	Launceston	Tasmania	Australia
76	Local Institution	Geelong	Victoria	Australia
77	Local Institution	Prahran	Victoria	Australia
78	Local Institution	Aalst		Belgium
79	Local Institution	AYE		Belgium
80	Local Institution	Borgerhout		Belgium
81	Local Institution	Genk-waterschei		Belgium
82	Local Institution	Gent		Belgium
83	Local Institution	Hasselt		Belgium
84	Local Institution	HUY		Belgium
85	Local Institution	Leuven		Belgium
86	Local Institution	Verviers		Belgium
87	Local Institution	Salvador	Bahia	Brazil
88	Local Institution	Goiania-go	Goias	Brazil
89	Local Institution	Belo Horizonte	Minas Gerais	Brazil
90	Local Institution	Campinas	Sao Paulo	Brazil
91	Local Institution	Sao Paulo, Sp	Sao Paulo	Brazil
92	Local Institution	Rio de Janeiro		Brazil
93	Local Institution	Calgary	Alberta	Canada
94	Local Institution	Victoria	British Columbia	Canada
95	Local Institution	Ajax	Ontario	Canada
96	Local Institution	Hamilton	Ontario	Canada
97	Local Institution	Rexdale	Ontario	Canada
98	Local Institution	Scarborough	Ontario	Canada
99	Local Institution	Toronto	Ontario	Canada
100	Local Institution	Weston	Ontario	Canada
101	Local Institution	Longueuil	Quebec	Canada
102	Local Institution	Montreal	Quebec	Canada
103	Local Institution	St-Lambert	Quebec	Canada
104	Local Institution	Ste-Foy	Quebec	Canada
105	Local Institution	Prague 2		Czech Republic
106	Local Institution	Prague 4		Czech Republic
107	Local Institution	Prague 9		Czech Republic
108	Local Institution	Usti Nad Labem		Czech Republic
109	Local Institution	Copenhagen Nv		Denmark
110	Local Institution	Copenhagen		Denmark
111	Local Institution	Abbeville		France
112	Local Institution	Cholet		France
113	Local Institution	DAX		France
114	Local Institution	GAP		France
115	Local Institution	Langres		France
116	Local Institution	Lille		France
117	Local Institution	Montbeliard		France
118	Local Institution	Paris Cedex 13		France
119	Local Institution	Poissy		France
120	Local Institution	Pontoise		France
121	Local Institution	Provins		France
122	Local Institution	Roubaix		France
123	Local Institution	Rouen		France
124	Local Institution	Saint Malo		France
125	Local Institution	Tours		France
126	Local Institution	Vandoeuvre Les Nancy		France
127	Local Institution	Vichy Cedex		France
128	Local Institution	Bad Homburg		Germany
129	Local Institution	Berlin		Germany
130	Local Institution	Goettingen		Germany
131	Local Institution	Gunzenhausen		Germany
132	Local Institution	Halle		Germany
133	Local Institution	Homburg / Saar		Germany
134	Local Institution	Jena		Germany
135	Local Institution	Langen		Germany
136	Local Institution	Leipzig		Germany
137	Local Institution	Mainz		Germany
138	Local Institution	Marburg		Germany
139	Local Institution	Muenchen		Germany
140	Local Institution	Regensburg		Germany
141	Local Institution	Stuttgart		Germany
142	Local Institution	Witten		Germany
143	Local Institution	Wuerzburg		Germany
144	Local Institution	Athens		Greece
145	Local Institution	Patras		Greece
146	Local Institution	Budapest		Hungary
147	Local Institution	Debrecen		Hungary
148	Local Institution	Siofok		Hungary
149	Local Institution	Szeged		Hungary
150	Local Institution	County Dublin	Dublin	Ireland
151	Local Institution	Dublin		Ireland
152	Local Institution	Ascoli Piceno		Italy
153	Local Institution	Bologna		Italy
154	Local Institution	Brescia		Italy
155	Local Institution	Cosenza		Italy
156	Local Institution	Pavia		Italy
157	Local Institution	Perugia		Italy
158	Local Institution	Piacenza		Italy
159	Local Institution	Roma		Italy
160	Local Institution	Siena		Italy
161	Local Institution	Trieste		Italy
162	Local Institution	Udine		Italy
163	Local Institution	Mexico	Distrito Federal	Mexico
164	Local Institution	Guadalajara	Jalisco	Mexico
165	Local Institution	San Pedro Garza Garcia	Nuevo Leon	Mexico
166	Local Institution	Aguascalientes		Mexico
167	Local Institution	Alkmaar		Netherlands
168	Local Institution	Almere		Netherlands
169	Local Institution	Amersfoort		Netherlands
170	Local Institution	Apeldoorn		Netherlands
171	Local Institution	Assen		Netherlands
172	Local Institution	Breda		Netherlands
173	Local Institution	Delft		Netherlands
174	Local Institution	Emmen		Netherlands
175	Local Institution	Gorinchem		Netherlands
176	Local Institution	Groningen		Netherlands
177	Local Institution	Heemstede		Netherlands
178	Local Institution	Helmond		Netherlands
179	Local Institution	Hengelo Ov		Netherlands
180	Local Institution	Nijmegen		Netherlands
181	Local Institution	Rotterdam		Netherlands
182	Local Institution	Sittard		Netherlands
183	Local Institution	Sneek		Netherlands
184	Local Institution	Veldhoven		Netherlands
185	Local Institution	Vlaardingen		Netherlands
186	Local Institution	Zaandam		Netherlands
187	Local Institution	Baerum Postterminal		Norway
188	Local Institution	Stavanger		Norway
189	Local Institution	Tonsberg		Norway
190	Local Institution	Bydgoszcz		Poland
191	Local Institution	Katowice		Poland
192	Local Institution	Piotrkow Tryb.		Poland
193	Local Institution	Stalowa Wola		Poland
194	Local Institution	Warszawa		Poland
195	Local Institution	Wroclaw		Poland
196	Local Institution	Lisbon		Portugal
197	Local Institution	Matosinhos		Portugal
198	Local Institution	Moscow		Russian Federation
199	Local Institution	Saratov		Russian Federation
200	Local Institution	St. Petersburg		Russian Federation
201	Local Institution	Johannesburg	Gauteng	South Africa
202	Local Institution	Morningside	Gauteng	South Africa
203	Local Institution	Parktown West	Gauteng	South Africa
204	Local Institution	Berea	Kwa Zulu Natal	South Africa
205	Local Institution	Congella	Kwa Zulu Natal	South Africa
206	Local Institution	A Coruna		Spain
207	Local Institution	Barcelona		Spain
208	Local Institution	Cordoba		Spain
209	Local Institution	Madrid		Spain
210	Local Institution	Malaga		Spain
211	Local Institution	Murcia		Spain
212	Local Institution	Palma de Mallorca		Spain
213	Local Institution	Sevilla		Spain
214	Local Institution	Valencia		Spain
215	Local Institution	Zaragoza		Spain
216	Local Institution	Falun		Sweden
217	Local Institution	Gothenburg		Sweden
218	Local Institution	Linkoping		Sweden
219	Local Institution	Malmo		Sweden
220	Local Institution	Skelleftea		Sweden
221	Local Institution	Stockholm		Sweden
222	Local Institution	Sundsvall		Sweden
223	Local Institution	Bellinzona		Switzerland
224	Local Institution	Liestal		Switzerland
225	Local Institution	Zuerich		Switzerland
226	Local Institution	Glasgow	Dumbartonshire	United Kingdom
227	Local Institution	Romford	Essex	United Kingdom
228	Local Institution	Hull	Yorkshire	United Kingdom
229	Local Institution	York	Yorkshire	United Kingdom
230	Local Institution	Dundee		United Kingdom
231	Local Institution	Londonderry		United Kingdom

Sponsors and Collaborators

• Bristol-Myers Squibb
• Sanofi

Investigators

• Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Bristol-Myers Squibb
• ClinicalTrials.gov Identifier: NCT00095238
• Other Study ID Numbers: CV131-148
• First Posted: Nov 2, 2004
• Last Update Posted: Apr 7, 2015
• Last Verified: Mar 1, 2015

• Additional relevant MeSH terms: Heart Failure; Irbesartan

Study Results

Participant Flow

Arm/Group Title	Irbesartan	Placebo
Arm/Group Description	titration from 75 to 300 mg, once daily (QD), up to 6 years	titration from 75 to 300 mg, once daily (QD), up to 6 years
Period Title: Overall Study
STARTED	2067	2061
Safety (Treated) Population	2064	2062
COMPLETED	1210	1209
NOT COMPLETED	857	852

Baseline Characteristics

Arm/Group Title	Irbesartan	Placebo	Total
Arm/Group Description	titration from 75 to 300 mg, once daily (QD), up to 6 years	titration from 75 to 300 mg, once daily (QD), up to 6 years	Total of all reporting groups
Overall Participants	2067	2061	4128
Age, Customized (participants) [Number]
< 65 years	376 18.2%	364 17.7%	740 17.9%
Between 65 and 74 years	994 48.1%	981 47.6%	1975 47.8%
>=75 years	697 33.7%	716 34.7%	1413 34.2%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	71.6 (6.90)	71.7 (7.00)	71.6 (6.95)
Sex: Female, Male (Count of Participants)
Female	1227 59.4%	1264 61.3%	2491 60.3%
Male	840 40.6%	797 38.7%	1637 39.7%
Race/Ethnicity, Customized (participants) [Number]
White	1934 93.6%	1925 93.4%	3859 93.5%
Black or African American	39 1.9%	43 2.1%	82 2%
Asian	19 0.9%	15 0.7%	34 0.8%
American Indian or Alaska Native	0 0%	0 0%	0 0%
Native Hawaiian or other Pacific Islander	0 0%	1 0%	1 0%
Other	75 3.6%	77 3.7%	152 3.7%
New York Heart Association (NYHA) Class (participants) [Number]
Class I (Mild)	0 0%	1 0%	1 0%
Class II (Mild)	426 20.6%	444 21.5%	870 21.1%
Class III (Moderate)	1582 76.5%	1562 75.8%	3144 76.2%
Class IV (Severe)	59 2.9%	53 2.6%	112 2.7%
B-Type Natriuretic Peptide (Pro-BNP) (pg/mL) [Geometric Mean (Inter-Quartile Range) ]
Geometric Mean (Inter-Quartile Range) [pg/mL]	363.0	345.2	353.9

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With First Occurrence of the Composite Outcome of Death (All Cause) or Protocol-Specified Cardiovascular (CV) Hospitalization at Given Timepoints
Description	Treatment comparisons for time to first occurrence of composite outcome of all-cause death (composite outcome of death) or protocol-specified CV hospitalization. Protocol-specified CV hospitalizations include those ≥24 hrs or involving a calendar date change for a primary cause of worsening heart failure, unstable angina, myocardial infarction, ventricular or atrial dysrhythmia, or stroke, that also require intravenous or intramuscular therapy or a related procedure or significant augmentation of oral therapy. In addition, MI or stroke during any hospitalization are included.
Time Frame	Year 1, Year 2, Year 3, Year 4, Year 5

Outcome Measure Data

Analysis Population Description

Randomized Participants

Arm/Group Title	Irbesartan	Placebo
Arm/Group Description	titration from 75 to 300 mg, once daily (QD), up to 6 years	titration from 75 to 300 mg, once daily (QD), up to 6 years
Measure Participants	2067	2061
Percentage at 1 Year	12.3 0.6%	12.1 0.6%
Percentage at 2 Years	20.7 1%	21.3 1%
Percentage at 3 Years	26.4 1.3%	28.4 1.4%
Percentage at 4 Years	32.9 1.6%	34.2 1.7%
Percentage at 5 Years	39.2 1.9%	39.5 1.9%

2. Secondary Outcome

Title	Percentage of Participants Experiencing Heart Failure Mortality or Heart Failure Hospitalization at Given Time Points
Description	Treatment comparisons for time to heart failure mortality or heart failure hospitalization
Time Frame	Year 1, Year 2, Year 3, Year 4, Year 5

Outcome Measure Data

Analysis Population Description

Randomized Participants

Arm/Group Title	Irbesartan	Placebo
Arm/Group Description	titration from 75 to 300 mg, once daily (QD), up to 6 years	titration from 75 to 300 mg, once daily (QD), up to 6 years
Measure Participants	2067	2061
Percentage at 1 Year	7.9 0.4%	8.2 0.4%
Percentage at 2 Years	12.9 0.6%	13.7 0.7%
Percentage at 3 Years	15.7 0.8%	17.2 0.8%
Percentage at 4 Years	19.8 1%	20.3 1%
Percentage at 5 Years	23.6 1.1%	23.8 1.2%

3. Secondary Outcome

Title	Minnesota Living With Heart Failure (MLwHF) Total Score (Sum of Questions 1-21) at Month 6 and Month 14
Description	Mean score and adjusted mean change from baseline in Minnesota Living with Heart Failure (MLWHF) questionnaire, a 21-item, patient-reported, 6-point (ranging from 0-5; higher score=poorer quality of life; highest possible score=105) measurement of quality of life in persons with heart failure.
Time Frame	Baseline, Month 6, Month 14

Outcome Measure Data

Analysis Population Description

Participants with baseline score and score at timepoint.

Arm/Group Title	Placebo - Month 6	Irbesartan - Month 6	Placebo - Month 14	Irbesartan - Month 14
Arm/Group Description	Cohort of participants in Placebo group with MLwHF scores at Baseline and Month 6	Cohort of participants in Irbesartan group with MLwHF scores at Baseline and Month 6	Cohort of participants in Placebo group with MLwHF scores at Baseline and Month 14	Cohort of participants in Irbesartan group with MLwHF scores at Baseline and Month 14
Measure Participants	1552	1550	1434	1428
Baseline Mean Score	42.7 (0.52)	43.0 (0.53)	42.7 (0.53)	42.8 (0.55)
Mean Score at Timepoint	32.9 (0.48)	33.2 (0.50)	31.6 (0.50)	32.1 (0.50)
Adjusted Mean Change from Baseline	-10.0 (0.41)	-9.8 (0.41)	-11.2 (0.42)	-10.6 (0.42)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Irbesartan, Placebo
	Comments	Comparison of 2 treatment arms at Month 6 (first 2 columns)
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.2
	Confidence Interval	(2-Sided) 95%; -0.8 to 1.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo - Month 14, Irbesartan - Month 14
	Comments	comparison of 2 treatment arms at Month 14 (columns 3 and 4)
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.6
	Confidence Interval	(2-Sided) 95%; -0.5 to 1.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Minnesota Living With Heart Failure (MLwHF) Total Score (Sum of Questions 1-21) at Final Visit
Description	Mean score at baseline and final visit in Minnesota Living with Heart Failure (MLWHF) questionnaire, a 21-item, patient-reported, 6-point (ranging from 0-5; higher score=poorer quality of life; highest possible score=105) measurement of quality of life in persons with heart failure.
Time Frame	Baseline, Final Visit=last scheduled visit specified in the protocol at conclusion of the entire study by the sponsor. The trial was designed to end after 1440 primary endpoint events, projected duration=6.0 ± 0.5 years.

Outcome Measure Data

Analysis Population Description

Participants with baseline score and score at timepoint.

Arm/Group Title	Placebo - Final Visit	Irbesartan - Final Visit
Arm/Group Description	Cohort of participants in Placebo group with MLwHF scores at Baseline and Final Visit	Cohort of participants in Irbesartan group with MLwHF scores at Baseline and Final Visit
Measure Participants	2067	2061
Baseline Mean	42.5 (0.49)	38.9 (0.67)
Final Visit Mean	42.6 (0.51)	38.3 (0.69)

5. Secondary Outcome

Title	Change From Baseline in B-Type Natriuretic Peptide (Pro-BNP) at Month 6 and Month 14
Description	Adjusted ratio to baseline in geometric mean in Pro-BNP in the blood. Ratio to Baseline = On-therapy geometric mean divided by baseline geometric mean. A lower score signifies improvement. Change from baseline adjusted for baseline value and angiotensin converting enzyme inhibitor use at baseline. Analysis uses natural logarithms of excretion rate values.
Time Frame	Baseline, Month 6, Month 14

Outcome Measure Data

Analysis Population Description

number of participants with measurement at baseline and at timepoint

Arm/Group Title	Placebo - Month 6	Irbesartan - Month 6	Placebo - Month 14	Irbesartan - Month 14
Arm/Group Description	Placebo cohort with measurements at baseline and Month 6.	Irbesartan cohort with measurements at Baseline and Month 6.	Placebo cohort with measurements at Baseline and Month 14.	Irbesartan cohort with measurements at Baseline and Month 14.
Measure Participants	1336	1337	1295	1281
Geometric Mean (Standard Error) [pg/mL]	0.98 (0.023)	0.93 (0.022)	1.00 (0.026)	1.01 (0.026)

6. Secondary Outcome

Title	Percentage of Participants Experiencing CV Death, Non-Fatal Myocardial Infarction (MI), or Non-Fatal Stroke at Given Timepoints
Description	Treatment comparisons for time to cardiovascular death, non-fatal MI, or non-fatal stroke.
Time Frame	Year 1, Year 2, Year 3, Year 4, Year 5

Outcome Measure Data

Analysis Population Description

Randomized Participants

Arm/Group Title	Irbesartan	Placebo
Arm/Group Description	titration from 75 to 300 mg, once daily (QD), up to 6 years	titration from 75 to 300 mg, once daily (QD), up to 6 years
Measure Participants	2067	2061
Percentage at 1 Year	5.2 0.3%	4.2 0.2%
Percentage at 2 Years	8.7 0.4%	9.3 0.5%
Percentage at 3 Years	12.9 0.6%	13.6 0.7%
Percentage at 4 Years	17.2 0.8%	17.6 0.9%
Percentage at 5 Years	23.0 1.1%	22.4 1.1%

7. Secondary Outcome

Title	Percentage of Participants Experiencing Cardiovascular Death at Given Timepoints
Description	Treatment comparisons for time to cardiovascular death
Time Frame	Year 1, Year 2, Year 3, Year 4, Year 5

Outcome Measure Data

Analysis Population Description

Randomized Subjects

Arm/Group Title	Irbesartan	Placebo
Arm/Group Description	titration from 75 to 300 mg, once daily (QD), up to 6 years	titration from 75 to 300 mg, once daily (QD), up to 6 years
Measure Participants	2067	2061
Percentage 1 Year	3.3 0.2%	3.0 0.1%
Percentage 2 Years	6.2 0.3%	6.5 0.3%
Percentage 3 Years	9.6 0.5%	10.0 0.5%
Percentage at 4 Years	13.0 0.6%	13.1 0.6%
Percentage at 5 Years	18.0 0.9%	17.1 0.8%

8. Secondary Outcome

Title	Percentage of Participants Experiencing All-cause Death at Given Time Points
Description	Treatment comparisons for time to all-cause death
Time Frame	Year 1, Year 2, Year 3, Year 4, Year 5

Outcome Measure Data

Analysis Population Description

Randomized subjects

Arm/Group Title	Irbesartan	Placebo
Arm/Group Description	titration from 75 to 300 mg, once daily (QD), up to 6 years	titration from 75 to 300 mg, once daily (QD), up to 6 years
Measure Participants	2067	2061
Percentage at 1 Year	4.1 0.2%	3.8 0.2%
Percentage at 2 Years	8.1 0.4%	8.6 0.4%
Percentage at 3 Years	12.8 0.6%	13.8 0.7%
Percentage at 4 Years	17.9 0.9%	18.5 0.9%
Percentage at 5 Years	25.0 1.2%	23.6 1.1%

9. Secondary Outcome

Title	Change From Baseline in the New York Heart Association (NYHA) Functional Class at Month 6, Month 10, Month 14, and Final Visit
Description	NYHA functional classification=4-tiered system relating symptoms to everyday activities & quality of life. (See Reporting Groups for description of each class.) Change of NYHA functional class from baseline was grouped into 3 categories: improved, unchanged, or worsened (based on case report form [CRF] assessment). If a post-randomization CRF assessment was missing or participant died, was hospitalized for worsening heart failure or discontinued study medication for worsening heart failure, the participant was classified as Major Event.
Time Frame	Baseline, Month 6, Month 10, Month 14, Final Visit. The trial was designed to end after 1440 primary endpoint events, projected duration=6.0 ± 0.5 years.

Outcome Measure Data

Analysis Population Description

Randomized participants with measurement at baseline and Month 6, Month 10, Month 14, and Final Visit

Arm/Group Title	Irbesartan Baseline Class I or II	Irbesartan Class III or IV	Irbesartan Baseline All Classes Combined	Placebo Baseline Class I or II	Placebo Class III or IV	Placebo Baseline All Classes Combined
Arm/Group Description	Class I (Mild): No limitation of physical activity. Ordinary physical activity does not cause undue fatigue, palpitation, or dyspnea (shortness of breath). Class II (Mild): Slight limitation of physical activity. Comfortable at rest, but ordinary physical activity results in fatigue, palpitation, or dyspnea.	Class III (Moderate): Marked limitation of physical activity. Comfortable at rest, but less than ordinary activity causes fatigue, palpitation, or dyspnea. Class IV (Severe): Unable to carry out any physical activity without discomfort. Symptoms of cardiac insufficiency at rest. If any physical activity is undertaken, discomfort is increased.
Measure Participants	426	1641	2067	445	1615	2060
Month 6 - Improved	55 2.7%	881 42.7%	936 22.7%	47 NaN	834 NaN	881 NaN
Month 6 - Unchanged	310 15%	656 31.8%	966 23.4%	338 NaN	678 NaN	1016 NaN
Month 6 - Worsened	41 2%	7 0.3%	48 1.2%	47 NaN	4 NaN	51 NaN
Month 6 - Major Event	2 0.1%	8 0.4%	10 0.2%	2 NaN	12 NaN	14 NaN
Month 6 - No Data	18 0.9%	89 4.3%	107 2.6%	11 NaN	87 NaN	98 NaN
Month 10 - Improved	44 2.1%	904 43.9%	948 23%	42 NaN	860 NaN	902 NaN
Month 10 - Unchanged	294 14.2%	617 29.9%	911 22.1%	317 NaN	622 NaN	939 NaN
Month 10 - Worsened	53 2.6%	5 0.2%	58 1.4%	63 NaN	8 NaN	71 NaN
Month 10 - Major Event	10 0.5%	31 1.5%	41 1%	9 NaN	33 NaN	42 NaN
Month 10 - No Data	25 1.2%	84 4.1%	109 2.6%	14 NaN	92 NaN	106 NaN
Month 14 - Improved	38 1.8%	895 43.4%	933 22.6%	39 NaN	863 NaN	902 NaN
Month 14 - Unchanged	287 13.9%	579 28.1%	866 21%	312 NaN	578 NaN	890 NaN
Month 14 - Worsened	50 2.4%	11 0.5%	61 1.5%	62 NaN	7 NaN	69 NaN
Month 14 - Major Event	22 1.1%	53 2.6%	75 1.8%	16 NaN	64 NaN	80 NaN
Month 14 - No Data	29 1.4%	103 5%	132 3.2%	16 NaN	103 NaN	119 NaN
Final Visit - Improved	42 2%	886 43%	928 22.5%	42 NaN	840 NaN	882 NaN
Final Visit - Unchanged	230 11.1%	428 20.8%	658 15.9%	254 NaN	440 NaN	694 NaN
Final Visit - Worsened	68 3.3%	29 1.4%	97 2.3%	78 NaN	29 NaN	107 NaN
Final Visit - Major Event	75 3.6%	249 12.1%	324 7.8%	66 NaN	254 NaN	320 NaN
Final Visit - No Data	11 0.5%	49 2.4%	60 1.5%	5 NaN	52 NaN	57 NaN

10. Secondary Outcome

Title	Physician Assessment of Heart Failure Status at Month 6, Month 14, and Final Visit Compared With Baseline
Description	This was an assessment of the change in overall physician opinion of change from baseline status. Assessments are directly based on the Case Report Form (CRF). If the post-randomization CRF assessment was missing and the subject died, was hospitalized for worsening heart failure, or discontinued study medication for worsening heart failure, the subject was considered as having a Major Event. Participants who are summarized under Major Events are categorized as Worsened Markedly.
Time Frame	Baseline, Month 6, Month 14, Final Visit. The trial was designed to end after 1440 primary endpoint events, projected duration=6.0 ± 0.5 years.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Irbesartan	Placebo
Arm/Group Description	titration from 75 to 300 mg, once daily (QD), up to 6 years	titration from 75 to 300 mg, once daily (QD), up to 6 years
Measure Participants	2067	2061
Month 6 - Improved Markedly	230 11.1%	198 9.6%
Month 6 - Improved Moderately	562 27.2%	575 27.9%
Month 6 - Improved Slightly	533 25.8%	529 25.7%
Month 6 - Unchanged	528 25.5%	541 26.2%
Month 6 - Worsened Slightly	60 2.9%	58 2.8%
Month 6 - Worsened Moderately	17 0.8%	16 0.8%
Month 6 - Worsened Markedly	0 0%	4 0.2%
Month 6 - Major Event	8 0.4%	8 0.4%
Month 6 - No Data	129 6.2%	132 6.4%
Month 14 - Improved Markedly	214 10.4%	195 9.5%
Month 14 - Improved Moderately	546 26.4%	537 26.1%
Month 14 - Improved Slightly	442 21.4%	435 21.1%
Month 14 - Unchanged	507 24.5%	548 26.6%
Month 14 - Worsened Slightly	72 3.5%	73 3.5%
Month 14 - Worsened Moderately	21 1%	19 0.9%
Month 14 - Worsened Markedly	5 0.2%	6 0.3%
Month 14 - Major Event	75 3.6%	79 3.8%
Month 14 - No Data	185 9%	169 8.2%
Final Visit - Improved Markedly	180 8.7%	186 9%
Final Visit - Improved Moderately	430 20.8%	367 17.8%
Final Visit - Improved Slightly	344 16.6%	361 17.5%
Final Visit - Unchanged	477 23.1%	504 24.5%
Final Visit - Worsened Slightly	117 5.7%	117 5.7%
Final Visit - Worsened Moderately	41 2%	56 2.7%
Final Visit - Worsened Markedly	23 1.1%	28 1.4%
Final Visit - Major Event	364 17.6%	350 17%
Final Visit - No Data	91 4.4%	92 4.5%

11. Secondary Outcome

Title	Participant Assessment of Heart Failure Status at Month 6, Month 14, and Final Visit Compared With Baseline
Description	Assessments are directly based on the Case Report Form (CRF). If the post-randomization CRF assessment was missing and the subject died, was hospitalized for worsening heart failure, or discontinued study medication for worsening heart failure, the subject was considered as having a Major Event. Participants who are summarized under Major Events are categorized as Worsened Markedly.
Time Frame	Baseline, Month 6, Month 14, Final Visit. The trial was designed to end after 1440 primary endpoint events, projected duration=6.0 ± 0.5 years.

Outcome Measure Data

Analysis Population Description

Randomized Participants

Arm/Group Title	Irbesartan	Placebo
Arm/Group Description	titration from 75 to 300 mg, once daily (QD), up to 6 years	titration from 75 to 300 mg, once daily (QD), up to 6 years
Measure Participants	2067	2061
Month 6 - Improved Markedly	235 11.4%	230 11.2%
Month 6 - Improved Moderately	552 26.7%	563 27.3%
Month 6 - Improved Slightly	529 25.6%	519 25.2%
Month 6 - Unchanged	537 26%	529 25.7%
Month 6 - Worsened Slightly	63 3%	69 3.3%
Month 6 - Worsened Moderately	13 0.6%	20 1%
Month 6 - Worsened Markedly	8 0.4%	8 0.4%
Month 6 - Major Event	8 0.4%	7 0.3%
Month 6 - No Data	122 5.9%	116 5.6%
Month 14 - Improved Markedly	234 11.3%	206 10%
Month 14 - Improved Moderately	532 25.7%	534 25.9%
Month 14 - Improved Slightly	461 22.3%	450 21.8%
Month 14 - Unchanged	503 24.3%	527 25.6%
Month 14 - Worsened Slightly	78 3.8%	82 4%
Month 14 - Worsened Moderately	30 1.5%	35 1.7%
Month 14 - Worsened Markedly	8 0.4%	7 0.3%
Month 14 - Major Event	68 3.3%	74 3.6%
Month 14 - No Data	153 7.4%	146 7.1%
Final Visit - Improved Markedly	207 10%	201 9.8%
Final Visit - Improved Moderately	378 18.3%	339 16.4%
Final Visit - Improved Slightly	332 16.1%	352 17.1%
Final Visit - Unchanged	480 23.2%	495 24%
Final Visit - Worsened Slightly	121 5.9%	109 5.3%
Final Visit - Worsened Moderately	52 2.5%	76 3.7%
Final Visit - Worsened Markedly	25 1.2%	28 1.4%
Final Visit - Major Event	396 19.2%	383 18.6%
Final Event - No Data	76 3.7%	78 3.8%

12. Secondary Outcome

Title	Participant Assessment of Fatigue at Month 6, Month 14, and Final Visit Compared With Baseline
Description	Assessments are directly based on the Case Report Form (CRF). If the post-randomization CRF assessment was missing and the subject died, was hospitalized for worsening heart failure, or discontinued study medication for worsening heart failure, the subject was considered as having a Major Event. Participants who are summarized under Major Events are categorized as Worsened Markedly.
Time Frame	Baseline, Month 6, Month 14, Final Visit. The trial was designed to end after 1440 primary endpoint events, projected duration=6.0 ± 0.5 years.

Outcome Measure Data

Analysis Population Description

Randomized Participants

Arm/Group Title	Irbesartan	Placebo
Arm/Group Description	titration from 75 to 300 mg, once daily (QD), up to 6 years	titration from 75 to 300 mg, once daily (QD), up to 6 years
Measure Participants	2067	2061
Month 6 - Improved Markedly	193 9.3%	200 9.7%
Month 6 - Improved Moderately	523 25.3%	519 25.2%
Month 6 - Improved Slightly	504 24.4%	471 22.9%
Month 6 - Unchanged	579 28%	596 28.9%
Month 6 - Worsened Slightly	97 4.7%	101 4.9%
Month 6 - Worsened Moderately	28 1.4%	38 1.8%
Month 6 - Worsened Markedly	13 0.6%	13 0.6%
Month 6 - Major Event	8 0.4%	7 0.3%
Month 6 - No Data	122 5.9%	116 5.6%
Month 14 - Improved Markedly	195 9.4%	182 8.8%
Month 14 - Improved Moderately	513 24.8%	489 23.7%
Month 14 - Improved Slightly	439 21.2%	443 21.5%
Month 14 - Unchanged	525 25.4%	559 27.1%
Month 14 - Worsened Slightly	115 5.6%	109 5.3%
Month 14 - Worsened Moderately	48 2.3%	43 2.1%
Month 14 - Worsened Markedly	11 0.5%	16 0.8%
Month 14 - Major Event	68 3.3%	74 3.6%
Month 14 - No Data	153 7.4%	146 7.1%
Final Visit - Improved Markedly	157 7.6%	178 8.6%
Final Visit - Improved Moderately	361 17.5%	300 14.6%
Final Visit - Improved Slightly	319 15.4%	337 16.4%
Final Visit - Unchanged	479 23.2%	477 23.1%
Final Visit - Worsened Slightly	166 8%	176 8.5%
Final Visit - Worsened Moderately	80 3.9%	90 4.4%
Final Visit - Worsened Markedly	34 1.6%	42 2%
Final Visit - Major Event	395 19.1%	383 18.6%
Final Visit - No Data	76 3.7%	78 3.8%

13. Secondary Outcome

Title	Participant Assessment of Dyspnea at Month 6, Month 14, and Final Visit Compared With Baseline
Description	Assessments are directly based on the Case Report Form (CRF). If the post-randomization CRF assessment was missing and the subject died, was hospitalized for worsening heart failure, or discontinued study medication for worsening heart failure, the subject was considered as having a Major Event. Participants who are summarized under Major Events are categorized as Worsened Markedly.
Time Frame	Baseline, Month 6, Month 14, Final Visit. The trial was designed to end after 1440 primary endpoint events, projected duration=6.0 ± 0.5 years.

Outcome Measure Data

Analysis Population Description

Randomized Participants

Arm/Group Title	Irbesartan	Placebo
Arm/Group Description	titration from 75 to 300 mg, once daily (QD), up to 6 years	titration from 75 to 300 mg, once daily (QD), up to 6 years
Measure Participants	2067	2061
Month 6 - Improved Markedly	255 12.3%	276 13.4%
Month 6 - Improved Moderately	549 26.6%	536 26%
Month 6 - Improved Slightly	512 24.8%	501 24.3%
Month 6 - Unchanged	508 24.6%	510 24.7%
Month 6 - Worsened Slightly	83 4%	83 4%
Month 6 - Worsened Moderately	22 1.1%	22 1.1%
Month 6 - Worsened Markedly	9 0.4%	10 0.5%
Month 6 - Major Event	8 0.4%	7 0.3%
Month 6 - No Data	121 5.9%	116 5.6%
Month 14 - Improved Markedly	247 11.9%	232 11.3%
Month 14 - Improved Moderately	519 25.1%	531 25.8%
Month 14 - Improved Slightly	460 22.3%	430 20.9%
Month 14 - Unchanged	476 23%	509 24.7%
Month 14 - Worsened Slightly	103 5%	90 4.4%
Month 14 - Worsened Moderately	28 1.4%	39 1.9%
Month 14 - Worsened Markedly	13 0.6%	10 0.5%
Month 14 - Major Event	68 3.3%	74 3.6%
Month 14 - No Data	153 7.4%	146 7.1%
Final Visit - Improved Markedly	213 10.3%	212 10.3%
Final Visit - Improved Moderately	382 18.5%	339 16.4%
Final Visit - Improved Slightly	328 15.9%	335 16.3%
Final Visit - Unchanged	460 22.3%	461 22.4%
Final Visit - Worsened Slightly	114 5.5%	145 7%
Final Visit - Worsened Moderately	64 3.1%	75 3.6%
Final Visit - Worsened Markedly	35 1.7%	32 1.6%
Final Visit - Major Event	395 19.1%	384 18.6%
Final Visit - No Data	76 3.7%	78 3.8%

14. Secondary Outcome

Title	Percentage of Participants Experiencing CV Death or CV Hospitalization at Given Timepoints
Description	Treatment comparisons for time to CV death or CV hospitalization. Protocol-specified CV hospitalizations include hospitalizations ≥24 hrs or involve a calendar date change for a primary cause of worsening heart failure, unstable angina, myocardial infarction, ventricular dysrhythmia, atrial dysrhythmia or stroke that also requires intravenous or intramuscular therapy or a related procedure or significant augmentation of oral therapy. Protocol specified CV hospitalizations also include myocardial infarction or stroke occurring during any hospitalization.
Time Frame	Year 1, Year 2, Year 3, Year 4, Year 5

Outcome Measure Data

Analysis Population Description

randomized participants

Arm/Group Title	Irbesartan	Placebo
Arm/Group Description	titration from 75 to 300 mg, once daily (QD), up to 6 years	titration from 75 to 300 mg, once daily (QD), up to 6 years
Measure Participants	2067	2061
Percentage at 1 Year	11.6 0.6%	11.4 0.6%
Percentage at 2 Years	19.2 0.9%	20.0 1%
Percentage at 3 Years	24.2 1.2%	25.8 1.3%
Percentage at 4 Years	30.0 1.5%	30.9 1.5%
Percentage at 5 Years	35.0 1.7%	35.8 1.7%

15. Secondary Outcome

Title	Percentage of Participants Experiencing Protocol-specified Cardiovascular (CV) Hospitalization at Given Timepoints
Description	Treatment comparisons for time to protocol-specified CV hospitalization. Protocol-specified CV hospitalizations include hospitalizations ≥24 hrs or involve a calendar date change for a primary cause of worsening heart failure, unstable angina, myocardial infarction, ventricular dysrhythmia, atrial dysrhythmia or stroke that also requires intravenous or intramuscular therapy or a related procedure or significant augmentation of oral therapy. Protocol specified CV hospitalizations also include myocardial infarction or stroke occurring during any hospitalization.
Time Frame	Year 1, Year 2, Year 3, Year 4, Year 5

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Irbesartan	Placebo
Arm/Group Description	titration from 75 to 300 mg, once daily (QD), up to 6 years	titration from 75 to 300 mg, once daily (QD), up to 6 years
Measure Participants	2067	2061
Percentage at 1 Year	9.7 0.5%	9.8 0.5%
Percentage at 2 Years	16.3 0.8%	17.1 0.8%
Percentage at 3 Years	20.5 1%	21.7 1.1%
Percentage at 4 Years	24.8 1.2%	25.9 1.3%
Percentage at 5 Years	28.5 1.4%	29.0 1.4%

16. Secondary Outcome

Title	Percentage of Participants With New Onset of Diabetes Among Subjects With No Prior Diabetes History at Given Timepoints
Description	Treatment comparisons for time to new onset of diabetes (from adverse event reporting) among subjects with no prior history of diabetes.
Time Frame	Year 1, Year 2, Year 3, Year 4, Year 5

Outcome Measure Data

Analysis Population Description

Randomized participants with no prior diabetes history

Arm/Group Title	Irbesartan	Placebo
Arm/Group Description	titration from 75 to 300 mg, once daily (QD), up to 6 years	titration from 75 to 300 mg, once daily (QD), up to 6 years
Measure Participants	1495	1496
Percentage at 1 Year	0.7 0%	1.2 0.1%
Percentage at 2 Years	2.1 0.1%	2.8 0.1%
Percentage at 3 Years	3.1 0.1%	3.9 0.2%
Percentage at 4 Years	4.6 0.2%	5.4 0.3%
Percentage at 5 Years	5.2 0.3%	6.2 0.3%

17. Secondary Outcome

Title	Mean Change From Baseline in Glomerular Filtration Rate (GFR) at Month 6, Month 18, and Month 30
Description	Based on the Cockcroft-Gault formula calculation, a commonly used surrogate marker to estimate creatinine clearance, which in turn is an approximate measure of GFR. It employs serum creatinine measurements and a patient's weight to predict the creatinine clearance. Adjusted for baseline GFR and angiotensin-converting enzyme inhibitor use at baseline (ACE-I). A decrease from baseline signifies worsening. The adjusted mean change from baseline value is from the model (calculated prior to rounding), whereas the other two points are the baseline mean and post mean.
Time Frame	Baseline, Month 6, Month 18, Month 30

Outcome Measure Data

Analysis Population Description

Participants with baseline score and score at timepoint.

Arm/Group Title	Placebo - Month 6	Irbesartan - Month 6	Placebo - Month 18	Irbesartan - Month 18	Placebo - Month 30	Irbesartan - Month 30
Arm/Group Description	Cohort of participants in Placebo group with GFR assessment at Baseline and Month 6	Cohort of participants in irbesartan group with GFR assessment at Baseline and Month 6	Cohort of participants in Placebo group with GFR assessment at Baseline and Month 18	Cohort of participants in irbesartan group with GFR assessment at Baseline and Month 18	Cohort of participants in Placebo group with GFR assessment at Baseline and Month 30	Cohort of participants in irbesartan group with GFR assessment at Baseline and Month 30
Measure Participants	1741	1734	1406	1379	1270	1225
Baseline Mean	73.02 (0.536)	73.13 (0.538)	73.58 (0.589)	73.49 (0.591)	73.34 (0.606)	74.37 (0.630)
Post-Baseline Mean	71.97 (0.527)	69.21 (0.562)	70.88 (0.583)	68.00 (0.596)	69.51 (0.589)	67.05 (0.595)
Adjusted Mean Change	-1.07 (0.393)	-3.91 (0.394)	-2.69 (0.436)	-5.50 (0.440)	-4.02 (0.442)	-7.12 (0.450)

18. Secondary Outcome

Title	Mean Change From Baseline in Glomerular Filtration Rate (GFR)at Month 42, Month 54, Month 66
Description	Based on the Cockcroft-Gault formula calculation, a commonly used surrogate marker to estimate creatinine clearance, which in turn is an approximate measure of GFR. It employs serum creatinine measurements and a patient's weight to predict the creatinine clearance. Adjusted for baseline GFR and angiotensin-converting enzyme inhibitor use at baseline (ACE-I). A decrease from baseline signifies worsening. The adjusted mean change from baseline value is from the model (calculated prior to rounding), whereas the other two points are the baseline mean and post mean.
Time Frame	Baseline, Month 42, Month 54, Month 66

Outcome Measure Data

Analysis Population Description

Participants with baseline score and score at timepoint.

Arm/Group Title	Placebo - Month 42	Irbesartan - Month 42	Placebo - Month 54	Irbesartan - Month 54	Placebo - Month 66	Irbesartan - Month 66
Arm/Group Description	Cohort of participants in Placebo group with GFR assessment at Baseline and Month 42	Cohort of participants in irbesartan group with GFR assessment at Baseline and Month 42	Cohort of participants in Placebo group with GFR assessment at Baseline and Month 54	Cohort of participants in Placebo group with GFR assessment at Baseline and Month 54	Cohort of participants in Placebo group with GFR assessment at Baseline and Month 66	Cohort of participants in irbesartan group with GFR assessment at Baseline and Month 66
Measure Participants	928	921	429	455	22	22
Baseline Mean	74.37 (0.715)	74.95 (0.711)	75.29 (1.075)	75.17 (1.052)	63.47 (5.596)	71.84 (5.919)
Post-Baseline Mean	71.34 (0.700)	67.48 (0.715)	72.65 (1.048)	68.24 (1.055)	60.09 (5.832)	64.85 (6.301)
Adjusted Mean Change	-3.14 (0.559)	-7.36 (0.561)	-2.63 (0.863)	-6.93 (0.838)	-4.91 (4.534)	-5.46 (4.534)

19. Secondary Outcome

Title	Number of Participants With New Onset Atrial Fibrillation (AF) Among Those With No Prior AF History or Evidence of AF on Baseline Electrocardiograph (ECG)
Description	Frequency of new onset AF in participants with no prior AF history or evidence of AF on baseline ECG. Stratified by use of angiotensin-converting enzyme (ACE) inhibitors and measured by adverse events reporting and final ECG recording read by the investigator.
Time Frame	Baseline, Final Visit

Outcome Measure Data

Analysis Population Description

Randomized subjects (total=4128) with no prior AF history or evidence of AF on baseline ECG, stratified by use of ACE-I

Arm/Group Title	Irbesartan + ACE-I Use	Placebo + ACE-I Use	Irbesartan no ACE-I Use	Placebo no ACE-I Use
Arm/Group Description
Measure Participants	538	510	1529	1551
No prior AF history or Evidence on Baseline ECG	366 17.7%	344 16.7%	1089 26.4%	1102 NaN
Participants with New Onset Atrial Fibrillation	35 1.7%	29 1.4%	103 2.5%	99 NaN

Adverse Events

Time Frame	SAEs: from start of study through last treatment +30 days; AEs: through the last dose +1 day.
Arm/Group Title	IRBESARTAN		PLACEBO
Arm/Group Description	titration from 75 to 300 mg, once daily (QD), up to 6 years		titration from 75 to 300 mg, once daily (QD), up to 6 years
All Cause Mortality
	IRBESARTAN		PLACEBO
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	IRBESARTAN		PLACEBO
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1146/2064 (55.5%)		1155/2062 (56%)
Blood and lymphatic system disorders
ANAEMIA	31/2064 (1.5%)		27/2062 (1.3%)
LEUKOPENIA	0/2064 (0%)		1/2062 (0%)
NEUTROPENIA	0/2064 (0%)		1/2062 (0%)
COAGULOPATHY	1/2064 (0%)		1/2062 (0%)
LEUKOCYTOSIS	2/2064 (0.1%)		0/2062 (0%)
LYMPHADENOPATHY	0/2064 (0%)		1/2062 (0%)
THROMBOCYTOPENIA	2/2064 (0.1%)		0/2062 (0%)
MICROCYTIC ANAEMIA	1/2064 (0%)		1/2062 (0%)
HYPOCHROMIC ANAEMIA	1/2064 (0%)		0/2062 (0%)
SPONTANEOUS HAEMATOMA	0/2064 (0%)		1/2062 (0%)
IRON DEFICIENCY ANAEMIA	2/2064 (0.1%)		1/2062 (0%)
LYMPHADENOPATHY MEDIASTINAL	0/2064 (0%)		1/2062 (0%)
ANAEMIA VITAMIN B12 DEFICIENCY	1/2064 (0%)		0/2062 (0%)
NORMOCHROMIC NORMOCYTIC ANAEMIA	1/2064 (0%)		0/2062 (0%)
Cardiac disorders
ARRHYTHMIA	15/2064 (0.7%)		11/2062 (0.5%)
BRADYCARDIA	14/2064 (0.7%)		13/2062 (0.6%)
TACHYCARDIA	10/2064 (0.5%)		4/2062 (0.2%)
PALPITATIONS	2/2064 (0.1%)		5/2062 (0.2%)
PERICARDITIS	0/2064 (0%)		3/2062 (0.1%)
SINUS ARREST	1/2064 (0%)		0/2062 (0%)
ATRIAL FLUTTER	15/2064 (0.7%)		11/2062 (0.5%)
CARDIAC ARREST	9/2064 (0.4%)		9/2062 (0.4%)
CARDIAC ASTHMA	2/2064 (0.1%)		7/2062 (0.3%)
ANGINA PECTORIS	59/2064 (2.9%)		61/2062 (3%)
ANGINA UNSTABLE	86/2064 (4.2%)		78/2062 (3.8%)
BRADYARRHYTHMIA	2/2064 (0.1%)		2/2062 (0.1%)
CARDIAC FAILURE	274/2064 (13.3%)		275/2062 (13.3%)
TACHYARRHYTHMIA	2/2064 (0.1%)		2/2062 (0.1%)
CARDIAC DISORDER	3/2064 (0.1%)		1/2062 (0%)
NODAL ARRHYTHMIA	1/2064 (0%)		2/2062 (0.1%)
SINOATRIAL BLOCK	0/2064 (0%)		2/2062 (0.1%)
SINUS ARRHYTHMIA	1/2064 (0%)		0/2062 (0%)
CARDIAC TAMPONADE	0/2064 (0%)		1/2062 (0%)
CARDIOGENIC SHOCK	5/2064 (0.2%)		6/2062 (0.3%)
SINUS BRADYCARDIA	5/2064 (0.2%)		1/2062 (0%)
SINUS TACHYCARDIA	1/2064 (0%)		0/2062 (0%)
ATRIAL TACHYCARDIA	2/2064 (0.1%)		0/2062 (0%)
BIFASCICULAR BLOCK	0/2064 (0%)		1/2062 (0%)
ATRIAL FIBRILLATION	105/2064 (5.1%)		104/2062 (5%)
BUNDLE BRANCH BLOCK	0/2064 (0%)		1/2062 (0%)
CARDIAC HYPERTROPHY	1/2064 (0%)		0/2062 (0%)
CONDUCTION DISORDER	1/2064 (0%)		0/2062 (0%)
DRESSLER'S SYNDROME	0/2064 (0%)		1/2062 (0%)
SICK SINUS SYNDROME	5/2064 (0.2%)		15/2062 (0.7%)
AORTIC VALVE DISEASE	1/2064 (0%)		2/2062 (0.1%)
MYOCARDIAL ISCHAEMIA	12/2064 (0.6%)		10/2062 (0.5%)
PERICARDIAL EFFUSION	1/2064 (0%)		0/2062 (0%)
ADAMS-STOKES SYNDROME	0/2064 (0%)		1/2062 (0%)
AORTIC VALVE STENOSIS	6/2064 (0.3%)		2/2062 (0.1%)
ARTERIOSPASM CORONARY	0/2064 (0%)		1/2062 (0%)
CARDIAC FAILURE ACUTE	5/2064 (0.2%)		2/2062 (0.1%)
CARDIAC VALVE DISEASE	0/2064 (0%)		1/2062 (0%)
INTRACARDIAC THROMBUS	0/2064 (0%)		1/2062 (0%)
MITRAL VALVE PROLAPSE	0/2064 (0%)		1/2062 (0%)
MITRAL VALVE STENOSIS	1/2064 (0%)		0/2062 (0%)
MYOCARDIAL INFARCTION	42/2064 (2%)		47/2062 (2.3%)
PAROXYSMAL ARRHYTHMIA	1/2064 (0%)		0/2062 (0%)
ATRIOVENTRICULAR BLOCK	2/2064 (0.1%)		7/2062 (0.3%)
VENTRICULAR ARRHYTHMIA	1/2064 (0%)		1/2062 (0%)
ACUTE CORONARY SYNDROME	15/2064 (0.7%)		14/2062 (0.7%)
CARDIAC FAILURE CHRONIC	2/2064 (0.1%)		1/2062 (0%)
CARDIOPULMONARY FAILURE	1/2064 (0%)		1/2062 (0%)
CARDIOVASCULAR DISORDER	0/2064 (0%)		2/2062 (0.1%)
CORONARY ARTERY DISEASE	16/2064 (0.8%)		15/2062 (0.7%)
PERICARDIAL HAEMORRHAGE	1/2064 (0%)		0/2062 (0%)
VENTRICULAR DYSFUNCTION	0/2064 (0%)		1/2062 (0%)
VENTRICULAR TACHYCARDIA	8/2064 (0.4%)		10/2062 (0.5%)
BUNDLE BRANCH BLOCK LEFT	0/2064 (0%)		2/2062 (0.1%)
CHORDAE TENDINAE RUPTURE	1/2064 (0%)		0/2062 (0%)
CORONARY ARTERY STENOSIS	5/2064 (0.2%)		2/2062 (0.1%)
CORONARY OSTIAL STENOSIS	0/2064 (0%)		1/2062 (0%)
ISCHAEMIC CARDIOMYOPATHY	0/2064 (0%)		1/2062 (0%)
LEFT VENTRICULAR FAILURE	3/2064 (0.1%)		6/2062 (0.3%)
VENTRICULAR FIBRILLATION	2/2064 (0.1%)		6/2062 (0.3%)
AORTIC VALVE INCOMPETENCE	1/2064 (0%)		1/2062 (0%)
BUNDLE BRANCH BLOCK RIGHT	1/2064 (0%)		1/2062 (0%)
CARDIO-RESPIRATORY ARREST	5/2064 (0.2%)		7/2062 (0.3%)
CORONARY ARTERY OCCLUSION	0/2064 (0%)		2/2062 (0.1%)
MITRAL VALVE INCOMPETENCE	3/2064 (0.1%)		1/2062 (0%)
RIGHT VENTRICULAR FAILURE	3/2064 (0.1%)		2/2062 (0.1%)
VENTRICULAR EXTRASYSTOLES	1/2064 (0%)		2/2062 (0.1%)
CARDIAC FAILURE CONGESTIVE	55/2064 (2.7%)		61/2062 (3%)
CORONARY ARTERY DISSECTION	1/2064 (0%)		0/2062 (0%)
HYPERTENSIVE HEART DISEASE	1/2064 (0%)		0/2062 (0%)
ACUTE MYOCARDIAL INFARCTION	39/2064 (1.9%)		33/2062 (1.6%)
LEFT VENTRICULAR DYSFUNCTION	1/2064 (0%)		0/2062 (0%)
LEFT VENTRICULAR HYPERTROPHY	0/2064 (0%)		1/2062 (0%)
SILENT MYOCARDIAL INFARCTION	2/2064 (0.1%)		0/2062 (0%)
SUPRAVENTRICULAR TACHYCARDIA	5/2064 (0.2%)		10/2062 (0.5%)
CARDIOVASCULAR DECONDITIONING	1/2064 (0%)		0/2062 (0%)
CORONARY ARTERY INSUFFICIENCY	3/2064 (0.1%)		0/2062 (0%)
ATRIOVENTRICULAR BLOCK COMPLETE	11/2064 (0.5%)		8/2062 (0.4%)
ARTERIOSCLEROSIS CORONARY ARTERY	3/2064 (0.1%)		0/2062 (0%)
SUPRAVENTRICULAR TACHYARRHYTHMIA	1/2064 (0%)		0/2062 (0%)
ATRIOVENTRICULAR BLOCK FIRST DEGREE	1/2064 (0%)		1/2062 (0%)
ATRIOVENTRICULAR BLOCK SECOND DEGREE	1/2064 (0%)		4/2062 (0.2%)
Congenital, familial and genetic disorders
HIP DYSPLASIA	0/2064 (0%)		1/2062 (0%)
Ear and labyrinth disorders
VERTIGO	9/2064 (0.4%)		8/2062 (0.4%)
DEAFNESS	1/2064 (0%)		0/2062 (0%)
TINNITUS	1/2064 (0%)		0/2062 (0%)
HYPOACUSIS	1/2064 (0%)		0/2062 (0%)
PRESBYACUSIS	1/2064 (0%)		0/2062 (0%)
MOTION SICKNESS	2/2064 (0.1%)		0/2062 (0%)
VERTIGO POSITIONAL	0/2064 (0%)		2/2062 (0.1%)
VESTIBULAR DISORDER	1/2064 (0%)		0/2062 (0%)
DEAFNESS NEUROSENSORY	0/2064 (0%)		1/2062 (0%)
Endocrine disorders
GOITRE	3/2064 (0.1%)		5/2062 (0.2%)
THYROIDITIS	0/2064 (0%)		1/2062 (0%)
HYPOTHYROIDISM	3/2064 (0.1%)		1/2062 (0%)
HYPERTHYROIDISM	2/2064 (0.1%)		1/2062 (0%)
THYROID DISORDER	0/2064 (0%)		1/2062 (0%)
BASEDOW'S DISEASE	1/2064 (0%)		0/2062 (0%)
HYPERPARATHYROIDISM	0/2064 (0%)		1/2062 (0%)
Eye disorders
CATARACT	16/2064 (0.8%)		10/2062 (0.5%)
DIPLOPIA	0/2064 (0%)		1/2062 (0%)
GLAUCOMA	0/2064 (0%)		3/2062 (0.1%)
MACULOPATHY	0/2064 (0%)		2/2062 (0.1%)
RETINOPATHY	0/2064 (0%)		1/2062 (0%)
IRIDOCYCLITIS	0/2064 (0%)		1/2062 (0%)
VISION BLURRED	0/2064 (0%)		2/2062 (0.1%)
MACULAR RUPTURE	0/2064 (0%)		1/2062 (0%)
ATROPHY OF GLOBE	1/2064 (0%)		0/2062 (0%)
RETINAL DETACHMENT	2/2064 (0.1%)		1/2062 (0%)
BLINDNESS UNILATERAL	1/2064 (0%)		0/2062 (0%)
CORNEAL DEGENERATION	0/2064 (0%)		1/2062 (0%)
DIABETIC RETINOPATHY	1/2064 (0%)		1/2062 (0%)
MACULAR DEGENERATION	0/2064 (0%)		1/2062 (0%)
ULCERATIVE KERATITIS	1/2064 (0%)		0/2062 (0%)
VITREOUS HAEMORRHAGE	1/2064 (0%)		0/2062 (0%)
VISUAL ACUITY REDUCED	1/2064 (0%)		0/2062 (0%)
RETINAL VEIN OCCLUSION	1/2064 (0%)		0/2062 (0%)
RETINAL ARTERY EMBOLISM	1/2064 (0%)		0/2062 (0%)
CONJUNCTIVAL HAEMORRHAGE	1/2064 (0%)		0/2062 (0%)
Gastrointestinal disorders
ILEUS	3/2064 (0.1%)		2/2062 (0.1%)
NAUSEA	4/2064 (0.2%)		10/2062 (0.5%)
APHAGIA	0/2064 (0%)		1/2062 (0%)
ASCITES	3/2064 (0.1%)		2/2062 (0.1%)
COLITIS	3/2064 (0.1%)		5/2062 (0.2%)
MELAENA	4/2064 (0.2%)		3/2062 (0.1%)
SUBILEUS	1/2064 (0%)		1/2062 (0%)
VOLVULUS	1/2064 (0%)		0/2062 (0%)
VOMITING	7/2064 (0.3%)		8/2062 (0.4%)
DIARRHOEA	8/2064 (0.4%)		6/2062 (0.3%)
DYSPEPSIA	3/2064 (0.1%)		0/2062 (0%)
ENTERITIS	3/2064 (0.1%)		0/2062 (0%)
FAECALOMA	2/2064 (0.1%)		0/2062 (0%)
GASTRITIS	7/2064 (0.3%)		6/2062 (0.3%)
DUODENITIS	1/2064 (0%)		0/2062 (0%)
PERITONITIS	2/2064 (0.1%)		0/2062 (0%)
SIGMOIDITIS	0/2064 (0%)		1/2062 (0%)
ANAL FISSURE	0/2064 (0%)		1/2062 (0%)
ANAL FISTULA	0/2064 (0%)		1/2062 (0%)
CONSTIPATION	2/2064 (0.1%)		4/2062 (0.2%)
DIVERTICULUM	2/2064 (0.1%)		2/2062 (0.1%)
HAEMATEMESIS	4/2064 (0.2%)		1/2062 (0%)
HAEMORRHOIDS	2/2064 (0.1%)		1/2062 (0%)
OESOPHAGITIS	1/2064 (0%)		1/2062 (0%)
PANCREATITIS	2/2064 (0.1%)		6/2062 (0.3%)
PEPTIC ULCER	1/2064 (0%)		2/2062 (0.1%)
RECTAL POLYP	1/2064 (0%)		0/2062 (0%)
ACUTE ABDOMEN	2/2064 (0.1%)		0/2062 (0%)
COLONIC POLYP	2/2064 (0.1%)		3/2062 (0.1%)
DENTAL CARIES	1/2064 (0%)		0/2062 (0%)
GASTRIC ULCER	5/2064 (0.2%)		4/2062 (0.2%)
HAEMATOCHEZIA	0/2064 (0%)		1/2062 (0%)
HIATUS HERNIA	0/2064 (0%)		2/2062 (0.1%)
ABDOMINAL MASS	1/2064 (0%)		1/2062 (0%)
ABDOMINAL PAIN	19/2064 (0.9%)		17/2062 (0.8%)
DUODENAL ULCER	4/2064 (0.2%)		5/2062 (0.2%)
FEMORAL HERNIA	1/2064 (0%)		0/2062 (0%)
GASTRIC POLYPS	1/2064 (0%)		1/2062 (0%)
CROHN'S DISEASE	0/2064 (0%)		1/2062 (0%)
ILEUS PARALYTIC	0/2064 (0%)		1/2062 (0%)
INGUINAL HERNIA	7/2064 (0.3%)		9/2062 (0.4%)
INTESTINAL MASS	0/2064 (0%)		1/2062 (0%)
ABDOMINAL HERNIA	1/2064 (0%)		3/2062 (0.1%)
DUODENAL FISTULA	1/2064 (0%)		0/2062 (0%)
INTESTINAL POLYP	2/2064 (0.1%)		0/2062 (0%)
MECHANICAL ILEUS	1/2064 (0%)		0/2062 (0%)
SPIGELIAN HERNIA	0/2064 (0%)		1/2062 (0%)
UMBILICAL HERNIA	5/2064 (0.2%)		0/2062 (0%)
COLITIS ISCHAEMIC	2/2064 (0.1%)		0/2062 (0%)
GASTRITIS EROSIVE	5/2064 (0.2%)		3/2062 (0.1%)
COLITIS ULCERATIVE	1/2064 (0%)		2/2062 (0.1%)
EROSIVE DUODENITIS	1/2064 (0%)		0/2062 (0%)
PANCREATITIS ACUTE	4/2064 (0.2%)		2/2062 (0.1%)
RECTAL HAEMORRHAGE	7/2064 (0.3%)		6/2062 (0.3%)
COLONIC OBSTRUCTION	2/2064 (0.1%)		0/2062 (0%)
GASTRIC HAEMORRHAGE	2/2064 (0.1%)		2/2062 (0.1%)
PANCREATIC NECROSIS	2/2064 (0.1%)		0/2062 (0%)
ABDOMINAL DISCOMFORT	2/2064 (0.1%)		2/2062 (0.1%)
ABDOMINAL PAIN LOWER	0/2064 (0%)		1/2062 (0%)
ABDOMINAL PAIN UPPER	5/2064 (0.2%)		2/2062 (0.1%)
MESENTERIC OCCLUSION	0/2064 (0%)		1/2062 (0%)
PANCREATITIS CHRONIC	3/2064 (0.1%)		1/2062 (0%)
INTESTINAL INFARCTION	2/2064 (0.1%)		0/2062 (0%)
GASTRITIS HAEMORRHAGIC	3/2064 (0.1%)		1/2062 (0%)
INTESTINAL HAEMORRHAGE	1/2064 (0%)		1/2062 (0%)
INTESTINAL OBSTRUCTION	4/2064 (0.2%)		6/2062 (0.3%)
LARGE INTESTINAL ULCER	1/2064 (0%)		0/2062 (0%)
MALLORY-WEISS SYNDROME	0/2064 (0%)		1/2062 (0%)
DIVERTICULUM INTESTINAL	1/2064 (0%)		6/2062 (0.3%)
IRRITABLE BOWEL SYNDROME	1/2064 (0%)		0/2062 (0%)
PEPTIC ULCER HAEMORRHAGE	1/2064 (0%)		0/2062 (0%)
GASTRIC ULCER HAEMORRHAGE	1/2064 (0%)		0/2062 (0%)
GASTRIC ULCER PERFORATION	2/2064 (0.1%)		0/2062 (0%)
GASTROINTESTINAL DISORDER	3/2064 (0.1%)		1/2062 (0%)
HAEMORRHOIDAL HAEMORRHAGE	0/2064 (0%)		1/2062 (0%)
INTRA-ABDOMINAL HAEMATOMA	0/2064 (0%)		1/2062 (0%)
PANCREATITIS HAEMORRHAGIC	0/2064 (0%)		1/2062 (0%)
PAPILLA OF VATER STENOSIS	0/2064 (0%)		2/2062 (0.1%)
DUODENAL ULCER HAEMORRHAGE	0/2064 (0%)		1/2062 (0%)
GASTROINTESTINAL ISCHAEMIA	0/2064 (0%)		1/2062 (0%)
HIATUS HERNIA, OBSTRUCTIVE	1/2064 (0%)		0/2062 (0%)
BOWEL MOVEMENT IRREGULARITY	0/2064 (0%)		1/2062 (0%)
FEMORAL HERNIA, OBSTRUCTIVE	1/2064 (0%)		0/2062 (0%)
INTRA-ABDOMINAL HAEMORRHAGE	1/2064 (0%)		0/2062 (0%)
LARGE INTESTINE PERFORATION	1/2064 (0%)		2/2062 (0.1%)
RETROPERITONEAL HAEMORRHAGE	1/2064 (0%)		0/2062 (0%)
ABDOMINAL HERNIA OBSTRUCTIVE	0/2064 (0%)		1/2062 (0%)
GASTROINTESTINAL HAEMORRHAGE	21/2064 (1%)		15/2062 (0.7%)
INGUINAL HERNIA, OBSTRUCTIVE	0/2064 (0%)		2/2062 (0.1%)
LARGE INTESTINAL HAEMORRHAGE	1/2064 (0%)		0/2062 (0%)
SMALL INTESTINAL OBSTRUCTION	2/2064 (0.1%)		1/2062 (0%)
THROMBOSIS MESENTERIC VESSEL	1/2064 (0%)		3/2062 (0.1%)
ABDOMINAL STRANGULATED HERNIA	1/2064 (0%)		1/2062 (0%)
UMBILICAL HERNIA, OBSTRUCTIVE	0/2064 (0%)		1/2062 (0%)
OESOPHAGEAL VARICES HAEMORRHAGE	0/2064 (0%)		2/2062 (0.1%)
GASTROOESOPHAGEAL REFLUX DISEASE	0/2064 (0%)		1/2062 (0%)
LOWER GASTROINTESTINAL HAEMORRHAGE	2/2064 (0.1%)		1/2062 (0%)
UPPER GASTROINTESTINAL HAEMORRHAGE	6/2064 (0.3%)		6/2062 (0.3%)
DIVERTICULUM INTESTINAL HAEMORRHAGIC	1/2064 (0%)		1/2062 (0%)
General disorders
PAIN	0/2064 (0%)		1/2062 (0%)
DEATH	5/2064 (0.2%)		9/2062 (0.4%)
POLYP	0/2064 (0%)		1/2062 (0%)
CHILLS	0/2064 (0%)		2/2062 (0.1%)
HERNIA	1/2064 (0%)		2/2062 (0.1%)
NODULE	1/2064 (0%)		0/2062 (0%)
OEDEMA	2/2064 (0.1%)		1/2062 (0%)
FATIGUE	4/2064 (0.2%)		3/2062 (0.1%)
MALAISE	8/2064 (0.4%)		5/2062 (0.2%)
PYREXIA	6/2064 (0.3%)		8/2062 (0.4%)
ASTHENIA	8/2064 (0.4%)		7/2062 (0.3%)
EFFUSION	0/2064 (0%)		1/2062 (0%)
NECROSIS	0/2064 (0%)		5/2062 (0.2%)
DYSPLASIA	1/2064 (0%)		0/2062 (0%)
ENANTHEMA	1/2064 (0%)		0/2062 (0%)
CHEST PAIN	75/2064 (3.6%)		81/2062 (3.9%)
SUDDEN DEATH	70/2064 (3.4%)		76/2062 (3.7%)
ADVERSE EVENT	0/2064 (0%)		1/2062 (0%)
CARDIAC DEATH	1/2064 (0%)		0/2062 (0%)
ACCIDENTAL DEATH	0/2064 (0%)		1/2062 (0%)
CHEST DISCOMFORT	4/2064 (0.2%)		5/2062 (0.2%)
GAIT DISTURBANCE	0/2064 (0%)		1/2062 (0%)
IMPAIRED HEALING	1/2064 (0%)		1/2062 (0%)
LOCALISED OEDEMA	0/2064 (0%)		1/2062 (0%)
PERFORATED ULCER	1/2064 (0%)		0/2062 (0%)
OEDEMA PERIPHERAL	8/2064 (0.4%)		11/2062 (0.5%)
ULCER HAEMORRHAGE	0/2064 (0%)		1/2062 (0%)
GENERALISED OEDEMA	0/2064 (0%)		1/2062 (0%)
MULTI-ORGAN FAILURE	5/2064 (0.2%)		2/2062 (0.1%)
PERIPHERAL COLDNESS	1/2064 (0%)		0/2062 (0%)
SUDDEN CARDIAC DEATH	6/2064 (0.3%)		11/2062 (0.5%)
ADVERSE DRUG REACTION	1/2064 (0%)		0/2062 (0%)
IMPLANT SITE HAEMATOMA	0/2064 (0%)		1/2062 (0%)
NON-CARDIAC CHEST PAIN	6/2064 (0.3%)		5/2062 (0.2%)
TEMPERATURE INTOLERANCE	1/2064 (0%)		0/2062 (0%)
CATHETER RELATED COMPLICATION	0/2064 (0%)		1/2062 (0%)
DRUG CHEMICAL INCOMPATIBILITY	0/2064 (0%)		1/2062 (0%)
MECHANICAL COMPLICATION OF IMPLANT	1/2064 (0%)		1/2062 (0%)
GENERAL PHYSICAL HEALTH DETERIORATION	8/2064 (0.4%)		7/2062 (0.3%)
Hepatobiliary disorders
JAUNDICE	1/2064 (0%)		3/2062 (0.1%)
HEPATITIS	0/2064 (0%)		2/2062 (0.1%)
CHOLANGITIS	1/2064 (0%)		2/2062 (0.1%)
CHOLESTASIS	1/2064 (0%)		1/2062 (0%)
BILIARY COLIC	2/2064 (0.1%)		1/2062 (0%)
CHOLECYSTITIS	12/2064 (0.6%)		8/2062 (0.4%)
CHOLELITHIASIS	21/2064 (1%)		25/2062 (1.2%)
LIVER DISORDER	1/2064 (0%)		1/2062 (0%)
BILE DUCT STONE	1/2064 (0%)		4/2062 (0.2%)
BILIARY FISTULA	0/2064 (0%)		1/2062 (0%)
HEPATIC FAILURE	0/2064 (0%)		2/2062 (0.1%)
HEPATITIS ACUTE	1/2064 (0%)		0/2062 (0%)
HEPATITIS TOXIC	1/2064 (0%)		0/2062 (0%)
HYDROCHOLECYSTIS	1/2064 (0%)		0/2062 (0%)
CARDIAC CIRRHOSIS	0/2064 (0%)		1/2062 (0%)
HEPATIC CIRRHOSIS	3/2064 (0.1%)		3/2062 (0.1%)
BILIARY DYSKINESIA	1/2064 (0%)		0/2062 (0%)
CHOLECYSTITIS ACUTE	5/2064 (0.2%)		3/2062 (0.1%)
GALLBLADDER DISORDER	1/2064 (0%)		0/2062 (0%)
HEPATORENAL SYNDROME	0/2064 (0%)		1/2062 (0%)
JAUNDICE CHOLESTATIC	0/2064 (0%)		1/2062 (0%)
ACUTE HEPATIC FAILURE	1/2064 (0%)		0/2062 (0%)
CHOLECYSTITIS CHRONIC	4/2064 (0.2%)		2/2062 (0.1%)
HEPATITIS CHOLESTATIC	1/2064 (0%)		0/2062 (0%)
AMPULLA OF VATER STENOSIS	0/2064 (0%)		1/2062 (0%)
HEPATIC FUNCTION ABNORMAL	1/2064 (0%)		0/2062 (0%)
Immune system disorders
AMYLOIDOSIS	0/2064 (0%)		1/2062 (0%)
SARCOIDOSIS	0/2064 (0%)		1/2062 (0%)
IODINE ALLERGY	1/2064 (0%)		0/2062 (0%)
HYPERSENSITIVITY	1/2064 (0%)		2/2062 (0.1%)
ANAPHYLACTIC REACTION	0/2064 (0%)		1/2062 (0%)
DRUG HYPERSENSITIVITY	1/2064 (0%)		0/2062 (0%)
Infections and infestations
SEPSIS	9/2064 (0.4%)		15/2062 (0.7%)
ABSCESS	1/2064 (0%)		1/2062 (0%)
CYSTITIS	1/2064 (0%)		3/2062 (0.1%)
FURUNCLE	1/2064 (0%)		0/2062 (0%)
GANGRENE	3/2064 (0.1%)		2/2062 (0.1%)
MASTITIS	0/2064 (0%)		1/2062 (0%)
RHINITIS	1/2064 (0%)		0/2062 (0%)
CARBUNCLE	0/2064 (0%)		1/2062 (0%)
INFLUENZA	2/2064 (0.1%)		0/2062 (0%)
PAROTITIS	0/2064 (0%)		1/2062 (0%)
PNEUMONIA	87/2064 (4.2%)		83/2062 (4%)
PYOTHORAX	0/2064 (0%)		1/2062 (0%)
SINUSITIS	1/2064 (0%)		0/2062 (0%)
UROSEPSIS	9/2064 (0.4%)		7/2062 (0.3%)
BRONCHITIS	31/2064 (1.5%)		30/2062 (1.5%)
CELLULITIS	11/2064 (0.5%)		22/2062 (1.1%)
ERYSIPELAS	8/2064 (0.4%)		9/2062 (0.4%)
LARYNGITIS	0/2064 (0%)		2/2062 (0.1%)
PARONYCHIA	2/2064 (0.1%)		0/2062 (0%)
URETHRITIS	0/2064 (0%)		1/2062 (0%)
ABSCESS JAW	1/2064 (0%)		0/2062 (0%)
BACTERAEMIA	2/2064 (0.1%)		1/2062 (0%)
PHARYNGITIS	1/2064 (0%)		1/2062 (0%)
TONSILLITIS	0/2064 (0%)		1/2062 (0%)
ABSCESS LIMB	1/2064 (0%)		3/2062 (0.1%)
APPENDICITIS	0/2064 (0%)		4/2062 (0.2%)
ENDOCARDITIS	0/2064 (0%)		4/2062 (0.2%)
OTITIS MEDIA	0/2064 (0%)		1/2062 (0%)
SEPTIC SHOCK	7/2064 (0.3%)		6/2062 (0.3%)
TUBERCULOSIS	0/2064 (0%)		3/2062 (0.1%)
BRONCHIOLITIS	0/2064 (0%)		1/2062 (0%)
HERPES ZOSTER	1/2064 (0%)		0/2062 (0%)
OSTEOMYELITIS	4/2064 (0.2%)		3/2062 (0.1%)
SALMONELLOSIS	0/2064 (0%)		1/2062 (0%)
DIVERTICULITIS	4/2064 (0.2%)		8/2062 (0.4%)
LUNG INFECTION	9/2064 (0.4%)		13/2062 (0.6%)
OTITIS EXTERNA	0/2064 (0%)		2/2062 (0.1%)
PYELONEPHRITIS	3/2064 (0.1%)		1/2062 (0%)
SINOBRONCHITIS	1/2064 (0%)		0/2062 (0%)
SUPERINFECTION	0/2064 (0%)		1/2062 (0%)
ACUTE SINUSITIS	1/2064 (0%)		0/2062 (0%)
ECHINOCOCCIASIS	0/2064 (0%)		1/2062 (0%)
GASTROENTERITIS	13/2064 (0.6%)		8/2062 (0.4%)
LOBAR PNEUMONIA	4/2064 (0.2%)		2/2062 (0.1%)
PNEUMONIA VIRAL	0/2064 (0%)		1/2062 (0%)
TOOTH INFECTION	0/2064 (0%)		1/2062 (0%)
VIRAL INFECTION	2/2064 (0.1%)		0/2062 (0%)
WOUND INFECTION	2/2064 (0.1%)		2/2062 (0.1%)
BRONCHITIS VIRAL	1/2064 (0%)		0/2062 (0%)
BRONCHOPNEUMONIA	10/2064 (0.5%)		6/2062 (0.3%)
PERIANAL ABSCESS	0/2064 (0%)		1/2062 (0%)
DIABETIC GANGRENE	0/2064 (0%)		1/2062 (0%)
TRACHEOBRONCHITIS	2/2064 (0.1%)		1/2062 (0%)
CELLULITIS ORBITAL	1/2064 (0%)		0/2062 (0%)
ESCHERICHIA SEPSIS	1/2064 (0%)		1/2062 (0%)
ABSCESS SOFT TISSUE	1/2064 (0%)		0/2062 (0%)
ARTHRITIS BACTERIAL	2/2064 (0.1%)		0/2062 (0%)
FUNGAL OESOPHAGITIS	0/2064 (0%)		1/2062 (0%)
INFECTED SKIN ULCER	0/2064 (0%)		1/2062 (0%)
LOCALISED INFECTION	3/2064 (0.1%)		5/2062 (0.2%)
HERPES ZOSTER OTICUS	0/2064 (0%)		1/2062 (0%)
NOSOCOMIAL INFECTION	0/2064 (0%)		1/2062 (0%)
PERITONEAL INFECTION	1/2064 (0%)		0/2062 (0%)
PYELONEPHRITIS ACUTE	1/2064 (0%)		1/2062 (0%)
SKIN GRAFT INFECTION	1/2064 (0%)		0/2062 (0%)
STREPTOCOCCAL SEPSIS	1/2064 (0%)		0/2062 (0%)
SUBCUTANEOUS ABSCESS	2/2064 (0.1%)		0/2062 (0%)
HAEMOPHILUS INFECTION	1/2064 (0%)		0/2062 (0%)
PERITONSILLAR ABSCESS	0/2064 (0%)		1/2062 (0%)
PSEUDOMONAS INFECTION	1/2064 (0%)		0/2062 (0%)
SOFT TISSUE INFECTION	0/2064 (0%)		1/2062 (0%)
SPINAL CORD INFECTION	0/2064 (0%)		1/2062 (0%)
ABDOMINAL WALL ABSCESS	1/2064 (0%)		0/2062 (0%)
ENDOCARDITIS BACTERIAL	0/2064 (0%)		1/2062 (0%)
INFECTED VARICOSE VEIN	1/2064 (0%)		0/2062 (0%)
PNEUMONIA PNEUMOCOCCAL	0/2064 (0%)		1/2062 (0%)
PULMONARY TUBERCULOSIS	0/2064 (0%)		2/2062 (0.1%)
PYELONEPHRITIS CHRONIC	0/2064 (0%)		3/2062 (0.1%)
OESOPHAGEAL CANDIDIASIS	0/2064 (0%)		1/2062 (0%)
PNEUMONIA STREPTOCOCCAL	1/2064 (0%)		1/2062 (0%)
RETROPERITONEAL ABSCESS	1/2064 (0%)		0/2062 (0%)
STREPTOCOCCAL INFECTION	1/2064 (0%)		0/2062 (0%)
URINARY TRACT INFECTION	24/2064 (1.2%)		32/2062 (1.6%)
HERPES ZOSTER OPHTHALMIC	0/2064 (0%)		1/2062 (0%)
STAPHYLOCOCCAL INFECTION	3/2064 (0.1%)		0/2062 (0%)
PHARYNGITIS STREPTOCOCCAL	0/2064 (0%)		1/2062 (0%)
POST PROCEDURAL INFECTION	1/2064 (0%)		0/2062 (0%)
GASTROINTESTINAL INFECTION	1/2064 (0%)		0/2062 (0%)
RESPIRATORY TRACT INFECTION	8/2064 (0.4%)		12/2062 (0.6%)
CLOSTRIDIUM DIFFICILE COLITIS	0/2064 (0%)		1/2062 (0%)
POSTOPERATIVE WOUND INFECTION	2/2064 (0.1%)		2/2062 (0.1%)
LOWER RESPIRATORY TRACT INFECTION	4/2064 (0.2%)		4/2062 (0.2%)
RESPIRATORY TRACT INFECTION VIRAL	1/2064 (0%)		0/2062 (0%)
UPPER RESPIRATORY TRACT INFECTION	4/2064 (0.2%)		1/2062 (0%)
ESCHERICHIA URINARY TRACT INFECTION	1/2064 (0%)		0/2062 (0%)
VIRAL UPPER RESPIRATORY TRACT INFECTION	0/2064 (0%)		1/2062 (0%)
INFECTIVE EXACERBATION OF CHRONIC OBSTRUCTIVE AIRWAYS DISEASE	0/2064 (0%)		1/2062 (0%)
Injury, poisoning and procedural complications
FALL	22/2064 (1.1%)		23/2062 (1.1%)
WOUND	1/2064 (0%)		1/2062 (0%)
INJURY	1/2064 (0%)		0/2062 (0%)
OVERDOSE	3/2064 (0.1%)		1/2062 (0%)
CONTUSION	3/2064 (0.1%)		3/2062 (0.1%)
CONCUSSION	5/2064 (0.2%)		2/2062 (0.1%)
EYE INJURY	1/2064 (0%)		0/2062 (0%)
ANIMAL BITE	0/2064 (0%)		1/2062 (0%)
EXCORIATION	1/2064 (0%)		0/2062 (0%)
HEAD INJURY	8/2064 (0.4%)		2/2062 (0.1%)
HEAT STROKE	1/2064 (0%)		0/2062 (0%)
LIMB INJURY	1/2064 (0%)		0/2062 (0%)
HIP FRACTURE	12/2064 (0.6%)		9/2062 (0.4%)
JOINT INJURY	2/2064 (0.1%)		0/2062 (0%)
RIB FRACTURE	3/2064 (0.1%)		5/2062 (0.2%)
THERMAL BURN	1/2064 (0%)		1/2062 (0%)
DRUG TOXICITY	1/2064 (0%)		1/2062 (0%)
HAND FRACTURE	0/2064 (0%)		1/2062 (0%)
ULNA FRACTURE	2/2064 (0.1%)		0/2062 (0%)
ANIMAL SCRATCH	0/2064 (0%)		1/2062 (0%)
ANKLE FRACTURE	2/2064 (0.1%)		5/2062 (0.2%)
DEVICE FAILURE	1/2064 (0%)		2/2062 (0.1%)
FEMUR FRACTURE	10/2064 (0.5%)		7/2062 (0.3%)
GUN SHOT WOUND	1/2064 (0%)		0/2062 (0%)
ILIUM FRACTURE	0/2064 (0%)		1/2062 (0%)
RETINAL INJURY	0/2064 (0%)		1/2062 (0%)
SKULL FRACTURE	1/2064 (0%)		0/2062 (0%)
SUTURE RUPTURE	1/2064 (0%)		0/2062 (0%)
TIBIA FRACTURE	2/2064 (0.1%)		1/2062 (0%)
WRIST FRACTURE	2/2064 (0.1%)		2/2062 (0.1%)
BRAIN CONTUSION	1/2064 (0%)		0/2062 (0%)
EYEBALL RUPTURE	1/2064 (0%)		0/2062 (0%)
FIBULA FRACTURE	1/2064 (0%)		0/2062 (0%)
PELVIC FRACTURE	3/2064 (0.1%)		3/2062 (0.1%)
RADIUS FRACTURE	4/2064 (0.2%)		1/2062 (0%)
SKELETAL INJURY	1/2064 (0%)		0/2062 (0%)
SKIN LACERATION	0/2064 (0%)		1/2062 (0%)
SPINAL FRACTURE	1/2064 (0%)		1/2062 (0%)
FOREARM FRACTURE	0/2064 (0%)		1/2062 (0%)
FRACTURED SACRUM	0/2064 (0%)		1/2062 (0%)
HUMERUS FRACTURE	1/2064 (0%)		1/2062 (0%)
LIGAMENT RUPTURE	0/2064 (0%)		1/2062 (0%)
PATELLA FRACTURE	0/2064 (0%)		1/2062 (0%)
STERNAL FRACTURE	0/2064 (0%)		1/2062 (0%)
WOUND DEHISCENCE	1/2064 (0%)		0/2062 (0%)
ALCOHOL POISONING	2/2064 (0.1%)		1/2062 (0%)
CLAVICLE FRACTURE	1/2064 (0%)		1/2062 (0%)
JOINT DISLOCATION	3/2064 (0.1%)		2/2062 (0.1%)
MULTIPLE INJURIES	1/2064 (0%)		1/2062 (0%)
BURNS THIRD DEGREE	1/2064 (0%)		0/2062 (0%)
DEVICE DISLOCATION	0/2064 (0%)		1/2062 (0%)
SUBDURAL HAEMATOMA	3/2064 (0.1%)		2/2062 (0.1%)
TRAUMATIC FRACTURE	0/2064 (0%)		1/2062 (0%)
LOWER LIMB FRACTURE	4/2064 (0.2%)		1/2062 (0%)
PUBIC RAMI FRACTURE	0/2064 (0%)		2/2062 (0.1%)
UPPER LIMB FRACTURE	4/2064 (0.2%)		2/2062 (0.1%)
COMPRESSION FRACTURE	1/2064 (0%)		1/2062 (0%)
EXTRADURAL HAEMATOMA	1/2064 (0%)		0/2062 (0%)
HAEMATURIA TRAUMATIC	0/2064 (0%)		1/2062 (0%)
POSTOPERATIVE HERNIA	1/2064 (0%)		0/2062 (0%)
SUBDURAL HAEMORRHAGE	2/2064 (0.1%)		0/2062 (0%)
ANAEMIA POSTOPERATIVE	0/2064 (0%)		1/2062 (0%)
CARDIAC VALVE RUPTURE	1/2064 (0%)		0/2062 (0%)
CHEMICAL BURN OF SKIN	0/2064 (0%)		1/2062 (0%)
FACIAL BONES FRACTURE	0/2064 (0%)		1/2062 (0%)
FEMORAL NECK FRACTURE	1/2064 (0%)		2/2062 (0.1%)
ROAD TRAFFIC ACCIDENT	1/2064 (0%)		3/2062 (0.1%)
SUBCUTANEOUS HAEMATOMA	1/2064 (0%)		0/2062 (0%)
EXPOSURE TO TOXIC AGENT	0/2064 (0%)		1/2062 (0%)
TRACHEOSTOMY MALFUNCTION	1/2064 (0%)		0/2062 (0%)
VASCULAR GRAFT OCCLUSION	1/2064 (0%)		0/2062 (0%)
DEVICE ELECTRICAL FINDING	0/2064 (0%)		3/2062 (0.1%)
POST PROCEDURAL HAEMATURIA	1/2064 (0%)		0/2062 (0%)
THERAPEUTIC AGENT TOXICITY	2/2064 (0.1%)		2/2062 (0.1%)
CERVICAL VERTEBRAL FRACTURE	0/2064 (0%)		1/2062 (0%)
MEDICAL DEVICE COMPLICATION	1/2064 (0%)		1/2062 (0%)
SPINAL COMPRESSION FRACTURE	1/2064 (0%)		2/2062 (0.1%)
THORACIC VERTEBRAL FRACTURE	0/2064 (0%)		1/2062 (0%)
VASCULAR GRAFT COMPLICATION	1/2064 (0%)		0/2062 (0%)
CARDIAC PACEMAKER MALFUNCTION	11/2064 (0.5%)		3/2062 (0.1%)
ARTERIOVENOUS GRAFT THROMBOSIS	0/2064 (0%)		2/2062 (0.1%)
DISLOCATION OF JOINT PROSTHESIS	0/2064 (0%)		1/2062 (0%)
Investigations
ANGIOGRAM	0/2064 (0%)		1/2062 (0%)
WEIGHT DECREASED	2/2064 (0.1%)		4/2062 (0.2%)
TROPONIN INCREASED	0/2064 (0%)		1/2062 (0%)
BLOOD URINE PRESENT	0/2064 (0%)		1/2062 (0%)
BLOOD UREA INCREASED	0/2064 (0%)		1/2062 (0%)
CHEST X-RAY ABNORMAL	0/2064 (0%)		1/2062 (0%)
HAEMOGLOBIN ABNORMAL	1/2064 (0%)		0/2062 (0%)
HEART RATE INCREASED	0/2064 (0%)		2/2062 (0.1%)
BLOOD GLUCOSE ABNORMAL	1/2064 (0%)		0/2062 (0%)
BLOOD ALCOHOL INCREASED	0/2064 (0%)		1/2062 (0%)
BLOOD GLUCOSE INCREASED	1/2064 (0%)		3/2062 (0.1%)
BLOOD PRESSURE INCREASED	4/2064 (0.2%)		5/2062 (0.2%)
ELECTROCARDIOGRAM CHANGE	0/2064 (0%)		2/2062 (0.1%)
BLOOD POTASSIUM DECREASED	0/2064 (0%)		1/2062 (0%)
BLOOD POTASSIUM INCREASED	1/2064 (0%)		1/2062 (0%)
BLOOD CREATININE INCREASED	1/2064 (0%)		2/2062 (0.1%)
COAGULATION TIME PROLONGED	0/2064 (0%)		1/2062 (0%)
ELECTROCARDIOGRAM ABNORMAL	1/2064 (0%)		0/2062 (0%)
PROTHROMBIN TIME PROLONGED	1/2064 (0%)		0/2062 (0%)
RESPIRATORY RATE DECREASED	1/2064 (0%)		0/2062 (0%)
CARCINOEMBRYONIC ANTIGEN INCREASED	0/2064 (0%)		1/2062 (0%)
SCAN MYOCARDIAL PERFUSION ABNORMAL	1/2064 (0%)		0/2062 (0%)
BLOOD PRESSURE ORTHOSTATIC ABNORMAL	0/2064 (0%)		1/2062 (0%)
PULMONARY ARTERIAL PRESSURE INCREASED	1/2064 (0%)		0/2062 (0%)
INTERNATIONAL NORMALISED RATIO INCREASED	2/2064 (0.1%)		4/2062 (0.2%)
Metabolism and nutrition disorders
GOUT	2/2064 (0.1%)		5/2062 (0.2%)
OBESITY	0/2064 (0%)		2/2062 (0.1%)
ANOREXIA	3/2064 (0.1%)		0/2062 (0%)
CACHEXIA	2/2064 (0.1%)		0/2062 (0%)
DEHYDRATION	21/2064 (1%)		18/2062 (0.9%)
HYPOKALAEMIA	2/2064 (0.1%)		10/2062 (0.5%)
HYPOVOLAEMIA	1/2064 (0%)		1/2062 (0%)
MALNUTRITION	0/2064 (0%)		1/2062 (0%)
DIABETIC FOOT	6/2064 (0.3%)		0/2062 (0%)
HYPERKALAEMIA	11/2064 (0.5%)		8/2062 (0.4%)
HYPOCALCAEMIA	0/2064 (0%)		1/2062 (0%)
HYPOGLYCAEMIA	16/2064 (0.8%)		8/2062 (0.4%)
HYPONATRAEMIA	3/2064 (0.1%)		3/2062 (0.1%)
HYPERCALCAEMIA	0/2064 (0%)		1/2062 (0%)
HYPERGLYCAEMIA	3/2064 (0.1%)		2/2062 (0.1%)
FLUID RETENTION	1/2064 (0%)		0/2062 (0%)
DIABETES MELLITUS	11/2064 (0.5%)		19/2062 (0.9%)
FAILURE TO THRIVE	0/2064 (0%)		2/2062 (0.1%)
FOLATE DEFICIENCY	1/2064 (0%)		0/2062 (0%)
DECREASED APPETITE	1/2064 (0%)		0/2062 (0%)
HYPEROSMOLAR STATE	0/2064 (0%)		1/2062 (0%)
METABOLIC ACIDOSIS	1/2064 (0%)		0/2062 (0%)
METABOLIC DISORDER	2/2064 (0.1%)		0/2062 (0%)
TYPE 1 DIABETES MELLITUS	0/2064 (0%)		1/2062 (0%)
TYPE 2 DIABETES MELLITUS	1/2064 (0%)		1/2062 (0%)
DIABETES MELLITUS INADEQUATE CONTROL	3/2064 (0.1%)		5/2062 (0.2%)
Musculoskeletal and connective tissue disorders
MYALGIA	2/2064 (0.1%)		2/2062 (0.1%)
BURSITIS	3/2064 (0.1%)		1/2062 (0%)
MYOPATHY	0/2064 (0%)		1/2062 (0%)
OSTEITIS	2/2064 (0.1%)		0/2062 (0%)
ARTHRITIS	8/2064 (0.4%)		3/2062 (0.1%)
BACK PAIN	13/2064 (0.6%)		11/2062 (0.5%)
BONE PAIN	2/2064 (0.1%)		4/2062 (0.2%)
EXOSTOSIS	3/2064 (0.1%)		1/2062 (0%)
NECK PAIN	1/2064 (0%)		0/2062 (0%)
SCOLIOSIS	0/2064 (0%)		1/2062 (0%)
ARTHRALGIA	8/2064 (0.4%)		7/2062 (0.3%)
GROIN PAIN	0/2064 (0%)		1/2062 (0%)
OSTEOLYSIS	1/2064 (0%)		0/2062 (0%)
PAIN IN JAW	0/2064 (0%)		1/2062 (0%)
SPONDYLITIS	0/2064 (0%)		1/2062 (0%)
GOUTY TOPHUS	0/2064 (0%)		1/2062 (0%)
OSTEOPOROSIS	3/2064 (0.1%)		1/2062 (0%)
SACROILIITIS	0/2064 (0%)		1/2062 (0%)
HAEMARTHROSIS	0/2064 (0%)		1/2062 (0%)
METATARSALGIA	0/2064 (0%)		1/2062 (0%)
OSTEONECROSIS	0/2064 (0%)		1/2062 (0%)
FOOT DEFORMITY	0/2064 (0%)		3/2062 (0.1%)
JOINT EFFUSION	0/2064 (0%)		1/2062 (0%)
OSTEOARTHRITIS	37/2064 (1.8%)		24/2062 (1.2%)
COSTOCHONDRITIS	0/2064 (0%)		1/2062 (0%)
GOUTY ARTHRITIS	0/2064 (0%)		1/2062 (0%)
MUSCLE DISORDER	0/2064 (0%)		1/2062 (0%)
OSTEOCHONDROSIS	5/2064 (0.2%)		2/2062 (0.1%)
FLOATING PATELLA	1/2064 (0%)		0/2062 (0%)
ACQUIRED CLAW TOE	0/2064 (0%)		1/2062 (0%)
MUSCULAR WEAKNESS	2/2064 (0.1%)		5/2062 (0.2%)
PAIN IN EXTREMITY	3/2064 (0.1%)		6/2062 (0.3%)
SPONDYLOLISTHESIS	1/2064 (0%)		0/2062 (0%)
MUSCLE HAEMORRHAGE	1/2064 (0%)		0/2062 (0%)
COMPARTMENT SYNDROME	0/2064 (0%)		1/2062 (0%)
LOWER LIMB DEFORMITY	0/2064 (0%)		1/2062 (0%)
MUSCULOSKELETAL PAIN	0/2064 (0%)		2/2062 (0.1%)
RHEUMATOID ARTHRITIS	3/2064 (0.1%)		1/2062 (0%)
PATHOLOGICAL FRACTURE	2/2064 (0.1%)		1/2062 (0%)
ROTATOR CUFF SYNDROME	1/2064 (0%)		2/2062 (0.1%)
SPINAL OSTEOARTHRITIS	1/2064 (0%)		1/2062 (0%)
LUMBAR SPINAL STENOSIS	2/2064 (0.1%)		2/2062 (0.1%)
POLYMYALGIA RHEUMATICA	1/2064 (0%)		1/2062 (0%)
SPINAL COLUMN STENOSIS	1/2064 (0%)		4/2062 (0.2%)
NEUROPATHIC ARTHROPATHY	0/2064 (0%)		1/2062 (0%)
MUSCULOSKELETAL STIFFNESS	1/2064 (0%)		0/2062 (0%)
MUSCULOSKELETAL CHEST PAIN	1/2064 (0%)		3/2062 (0.1%)
INTERVERTEBRAL DISC DISORDER	1/2064 (0%)		0/2062 (0%)
SYSTEMIC LUPUS ERYTHEMATOSUS	1/2064 (0%)		0/2062 (0%)
INTERVERTEBRAL DISC PROTRUSION	3/2064 (0.1%)		6/2062 (0.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
LIPOMA	1/2064 (0%)		2/2062 (0.1%)
LYMPHOMA	0/2064 (0%)		1/2062 (0%)
MENINGIOMA	3/2064 (0.1%)		1/2062 (0%)
METASTASIS	2/2064 (0.1%)		2/2062 (0.1%)
SKIN CANCER	2/2064 (0.1%)		3/2062 (0.1%)
COLON CANCER	10/2064 (0.5%)		5/2062 (0.2%)
LIP NEOPLASM	0/2064 (0%)		1/2062 (0%)
RENAL CANCER	0/2064 (0%)		2/2062 (0.1%)
BONE NEOPLASM	1/2064 (0%)		0/2062 (0%)
BREAST CANCER	10/2064 (0.5%)		10/2062 (0.5%)
COLON ADENOMA	2/2064 (0.1%)		0/2062 (0%)
LUNG NEOPLASM	2/2064 (0.1%)		1/2062 (0%)
NEOPLASM SKIN	0/2064 (0%)		1/2062 (0%)
RECTAL CANCER	2/2064 (0.1%)		2/2062 (0.1%)
TONSIL CANCER	0/2064 (0%)		1/2062 (0%)
ADENOCARCINOMA	2/2064 (0.1%)		4/2062 (0.2%)
ADENOMA BENIGN	1/2064 (0%)		0/2062 (0%)
BLADDER CANCER	4/2064 (0.2%)		4/2062 (0.2%)
BRAIN NEOPLASM	1/2064 (0%)		1/2062 (0%)
COLON NEOPLASM	0/2064 (0%)		1/2062 (0%)
GASTRIC CANCER	6/2064 (0.3%)		5/2062 (0.2%)
OVARIAN CANCER	0/2064 (0%)		4/2062 (0.2%)
THYROID CANCER	0/2064 (0%)		2/2062 (0.1%)
UTERINE CANCER	1/2064 (0%)		0/2062 (0%)
BREAST NEOPLASM	0/2064 (0%)		1/2062 (0%)
PROSTATE CANCER	12/2064 (0.6%)		7/2062 (0.3%)
RECTAL NEOPLASM	0/2064 (0%)		1/2062 (0%)
THYROID ADENOMA	1/2064 (0%)		0/2062 (0%)
TRACHEAL CANCER	0/2064 (0%)		1/2062 (0%)
URETHRAL CANCER	0/2064 (0%)		1/2062 (0%)
ADRENAL NEOPLASM	1/2064 (0%)		0/2062 (0%)
BILE DUCT CANCER	1/2064 (0%)		1/2062 (0%)
BLADDER NEOPLASM	2/2064 (0.1%)		2/2062 (0.1%)
CARCINOID TUMOUR	1/2064 (0%)		0/2062 (0%)
CERVIX CARCINOMA	0/2064 (0%)		1/2062 (0%)
LARYNGEAL CANCER	1/2064 (0%)		0/2062 (0%)
MULTIPLE MYELOMA	2/2064 (0.1%)		1/2062 (0%)
OVARIAN NEOPLASM	3/2064 (0.1%)		0/2062 (0%)
PLEURAL NEOPLASM	0/2064 (0%)		1/2062 (0%)
THYROID NEOPLASM	1/2064 (0%)		0/2062 (0%)
BLADDER PAPILLOMA	0/2064 (0%)		1/2062 (0%)
NEOPLASM PROSTATE	0/2064 (0%)		1/2062 (0%)
PROSTATIC ADENOMA	2/2064 (0.1%)		3/2062 (0.1%)
UTERINE LEIOMYOMA	1/2064 (0%)		1/2062 (0%)
ABDOMINAL NEOPLASM	1/2064 (0%)		0/2062 (0%)
ENDOMETRIAL CANCER	1/2064 (0%)		1/2062 (0%)
GALLBLADDER CANCER	1/2064 (0%)		1/2062 (0%)
MALIGNANT MELANOMA	2/2064 (0.1%)		1/2062 (0%)
METASTASES TO BONE	1/2064 (0%)		1/2062 (0%)
NEOPLASM MALIGNANT	8/2064 (0.4%)		3/2062 (0.1%)
BRONCHIAL CARCINOMA	1/2064 (0%)		0/2062 (0%)
LUNG ADENOCARCINOMA	0/2064 (0%)		2/2062 (0.1%)
METASTASES TO LIVER	1/2064 (0%)		1/2062 (0%)
METASTASES TO SPINE	1/2064 (0%)		2/2062 (0.1%)
METASTATIC NEOPLASM	2/2064 (0.1%)		1/2062 (0%)
PANCREATIC NEOPLASM	0/2064 (0%)		1/2062 (0%)
BASAL CELL CARCINOMA	9/2064 (0.4%)		12/2062 (0.6%)
COLON CANCER STAGE 0	0/2064 (0%)		1/2062 (0%)
METASTASES TO PLEURA	1/2064 (0%)		0/2062 (0%)
PANCREATIC CARCINOMA	2/2064 (0.1%)		4/2062 (0.2%)
RENAL CELL CARCINOMA	0/2064 (0%)		1/2062 (0%)
OESOPHAGEAL CARCINOMA	1/2064 (0%)		1/2062 (0%)
RECTAL CANCER STAGE 0	1/2064 (0%)		0/2062 (0%)
SALIVARY GLAND CANCER	1/2064 (0%)		1/2062 (0%)
BENIGN BREAST NEOPLASM	1/2064 (0%)		0/2062 (0%)
COLON CANCER RECURRENT	0/2064 (0%)		1/2062 (0%)
LUNG CANCER METASTATIC	1/2064 (0%)		2/2062 (0.1%)
NON-HODGKIN'S LYMPHOMA	0/2064 (0%)		1/2062 (0%)
COLON CANCER METASTATIC	2/2064 (0.1%)		1/2062 (0%)
LUNG NEOPLASM MALIGNANT	7/2064 (0.3%)		8/2062 (0.4%)
SALIVARY GLAND NEOPLASM	1/2064 (0%)		0/2062 (0%)
SQUAMOUS CELL CARCINOMA	1/2064 (0%)		2/2062 (0.1%)
BREAST CANCER METASTATIC	0/2064 (0%)		1/2062 (0%)
CERVIX CARCINOMA STAGE 0	1/2064 (0%)		0/2062 (0%)
METASTASES TO PERITONEUM	0/2064 (0%)		1/2062 (0%)
PROSTATE CANCER STAGE IV	1/2064 (0%)		0/2062 (0%)
RETROPERITONEAL NEOPLASM	1/2064 (0%)		0/2062 (0%)
HEPATIC CANCER METASTATIC	0/2064 (0%)		1/2062 (0%)
MALIGNANT MUSCLE NEOPLASM	0/2064 (0%)		1/2062 (0%)
METASTATIC GASTRIC CANCER	1/2064 (0%)		2/2062 (0.1%)
HEPATIC NEOPLASM MALIGNANT	1/2064 (0%)		2/2062 (0.1%)
MALIGNANT PLEURAL EFFUSION	0/2064 (0%)		1/2062 (0%)
PROSTATE CANCER METASTATIC	1/2064 (0%)		0/2062 (0%)
BENIGN MEDIASTINAL NEOPLASM	0/2064 (0%)		1/2062 (0%)
MYELOPROLIFERATIVE DISORDER	1/2064 (0%)		0/2062 (0%)
CHRONIC LYMPHOCYTIC LEUKAEMIA	1/2064 (0%)		1/2062 (0%)
MALIGNANT FIBROUS HISTIOCYTOMA	1/2064 (0%)		0/2062 (0%)
SQUAMOUS CELL CARCINOMA OF SKIN	2/2064 (0.1%)		0/2062 (0%)
MALIGNANT URINARY TRACT NEOPLASM	1/2064 (0%)		0/2062 (0%)
WALDENSTROM'S MACROGLOBULINAEMIA	1/2064 (0%)		0/2062 (0%)
LENTIGO MALIGNA STAGE UNSPECIFIED	0/2064 (0%)		1/2062 (0%)
METASTATIC SQUAMOUS CELL CARCINOMA	0/2064 (0%)		1/2062 (0%)
CHRONIC LYMPHOCYTIC LEUKAEMIA STAGE 0	1/2064 (0%)		0/2062 (0%)
CHRONIC MYELOID LEUKAEMIA TRANSFORMATION	0/2064 (0%)		1/2062 (0%)
LUNG SQUAMOUS CELL CARCINOMA STAGE UNSPECIFIED	2/2064 (0.1%)		2/2062 (0.1%)
Nervous system disorders
COMA	0/2064 (0%)		1/2062 (0%)
TREMOR	0/2064 (0%)		1/2062 (0%)
SYNCOPE	36/2064 (1.7%)		41/2062 (2%)
DEMENTIA	0/2064 (0%)		3/2062 (0.1%)
EPILEPSY	2/2064 (0.1%)		1/2062 (0%)
HEADACHE	1/2064 (0%)		5/2062 (0.2%)
SCIATICA	3/2064 (0.1%)		2/2062 (0.1%)
DIZZINESS	9/2064 (0.4%)		12/2062 (0.6%)
HYPOTONIA	0/2064 (0%)		1/2062 (0%)
NEURALGIA	1/2064 (0%)		0/2062 (0%)
CONVULSION	0/2064 (0%)		4/2062 (0.2%)
DYSARTHRIA	1/2064 (0%)		0/2062 (0%)
HEMIPLEGIA	0/2064 (0%)		2/2062 (0.1%)
HYPERTONIA	3/2064 (0.1%)		1/2062 (0%)
MONOPLEGIA	0/2064 (0%)		1/2062 (0%)
PRESYNCOPE	5/2064 (0.2%)		4/2062 (0.2%)
SOMNOLENCE	0/2064 (0%)		1/2062 (0%)
HEMIPARESIS	0/2064 (0%)		2/2062 (0.1%)
MONOPARESIS	1/2064 (0%)		0/2062 (0%)
BRAIN INJURY	2/2064 (0.1%)		0/2062 (0%)
DROP ATTACKS	0/2064 (0%)		1/2062 (0%)
DYSAESTHESIA	1/2064 (0%)		0/2062 (0%)
PARAESTHESIA	0/2064 (0%)		2/2062 (0.1%)
SENSORY LOSS	0/2064 (0%)		1/2062 (0%)
HYPOAESTHESIA	1/2064 (0%)		0/2062 (0%)
EMBOLIC STROKE	1/2064 (0%)		0/2062 (0%)
ENCEPHALOPATHY	3/2064 (0.1%)		3/2062 (0.1%)
FACIAL PARESIS	1/2064 (0%)		1/2062 (0%)
GLOBAL AMNESIA	0/2064 (0%)		1/2062 (0%)
POLYNEUROPATHY	1/2064 (0%)		0/2062 (0%)
BALANCE DISORDER	2/2064 (0.1%)		0/2062 (0%)
CEREBROSCLEROSIS	0/2064 (0%)		1/2062 (0%)
ISCHAEMIC STROKE	14/2064 (0.7%)		25/2062 (1.2%)
PARTIAL SEIZURES	1/2064 (0%)		0/2062 (0%)
SPINAL HAEMATOMA	1/2064 (0%)		0/2062 (0%)
MENTAL IMPAIRMENT	2/2064 (0.1%)		1/2062 (0%)
MOTOR DYSFUNCTION	1/2064 (0%)		0/2062 (0%)
MYASTHENIA GRAVIS	0/2064 (0%)		1/2062 (0%)
SYNCOPE VASOVAGAL	2/2064 (0.1%)		0/2062 (0%)
VASCULAR DEMENTIA	1/2064 (0%)		0/2062 (0%)
CEREBRAL ISCHAEMIA	5/2064 (0.2%)		2/2062 (0.1%)
COGNITIVE DISORDER	0/2064 (0%)		1/2062 (0%)
MULTIPLE SCLEROSIS	1/2064 (0%)		0/2062 (0%)
RADICULAR SYNDROME	1/2064 (0%)		0/2062 (0%)
CEREBRAL INFARCTION	3/2064 (0.1%)		2/2062 (0.1%)
DIABETIC NEUROPATHY	0/2064 (0%)		3/2062 (0.1%)
HAEMORRHAGIC STROKE	5/2064 (0.2%)		4/2062 (0.2%)
PARKINSON'S DISEASE	1/2064 (0%)		1/2062 (0%)
SPINAL CLAUDICATION	1/2064 (0%)		0/2062 (0%)
WALLENBERG SYNDROME	1/2064 (0%)		0/2062 (0%)
CEREBELLAR HAEMATOMA	1/2064 (0%)		0/2062 (0%)
CEREBRAL HAEMORRHAGE	1/2064 (0%)		2/2062 (0.1%)
GRAND MAL CONVULSION	1/2064 (0%)		0/2062 (0%)
TOXIC ENCEPHALOPATHY	1/2064 (0%)		0/2062 (0%)
COORDINATION ABNORMAL	1/2064 (0%)		0/2062 (0%)
INTRACRANIAL ANEURYSM	1/2064 (0%)		0/2062 (0%)
LOSS OF CONSCIOUSNESS	3/2064 (0.1%)		2/2062 (0.1%)
CARPAL TUNNEL SYNDROME	2/2064 (0.1%)		2/2062 (0.1%)
HEPATIC ENCEPHALOPATHY	0/2064 (0%)		1/2062 (0%)
INTRACRANIAL HAEMATOMA	1/2064 (0%)		0/2062 (0%)
CAROTID ARTERY STENOSIS	7/2064 (0.3%)		5/2062 (0.2%)
SPINAL CORD COMPRESSION	3/2064 (0.1%)		2/2062 (0.1%)
VASCULAR ENCEPHALOPATHY	3/2064 (0.1%)		2/2062 (0.1%)
CAROTID ARTERY OCCLUSION	0/2064 (0%)		1/2062 (0%)
CEREBROVASCULAR ACCIDENT	56/2064 (2.7%)		70/2062 (3.4%)
CEREBROVASCULAR DISORDER	1/2064 (0%)		2/2062 (0.1%)
HAEMORRHAGE INTRACRANIAL	2/2064 (0.1%)		0/2062 (0%)
SUBARACHNOID HAEMORRHAGE	2/2064 (0.1%)		2/2062 (0.1%)
CEREBRAL ARTERIOSCLEROSIS	3/2064 (0.1%)		0/2062 (0%)
TRANSIENT ISCHAEMIC ATTACK	22/2064 (1.1%)		25/2062 (1.2%)
HYPERTENSIVE ENCEPHALOPATHY	0/2064 (0%)		1/2062 (0%)
INTRAVENTRICULAR HAEMORRHAGE	0/2064 (0%)		1/2062 (0%)
CEREBROVASCULAR INSUFFICIENCY	1/2064 (0%)		0/2062 (0%)
ISCHAEMIC CEREBRAL INFARCTION	0/2064 (0%)		1/2062 (0%)
VERTEBROBASILAR INSUFFICIENCY	3/2064 (0.1%)		0/2062 (0%)
ALTERED STATE OF CONSCIOUSNESS	0/2064 (0%)		1/2062 (0%)
DEPRESSED LEVEL OF CONSCIOUSNESS	2/2064 (0.1%)		0/2062 (0%)
HAEMORRHAGIC CEREBRAL INFARCTION	1/2064 (0%)		0/2062 (0%)
Psychiatric disorders
SOPOR	1/2064 (0%)		0/2062 (0%)
STRESS	1/2064 (0%)		0/2062 (0%)
ANXIETY	3/2064 (0.1%)		2/2062 (0.1%)
DELIRIUM	1/2064 (0%)		1/2062 (0%)
AGITATION	0/2064 (0%)		1/2062 (0%)
ALCOHOLISM	0/2064 (0%)		1/2062 (0%)
DEPRESSION	9/2064 (0.4%)		6/2062 (0.3%)
NERVOUSNESS	0/2064 (0%)		1/2062 (0%)
PANIC ATTACK	0/2064 (0%)		1/2062 (0%)
ALCOHOL ABUSE	1/2064 (0%)		1/2062 (0%)
HALLUCINATION	0/2064 (0%)		1/2062 (0%)
DISORIENTATION	2/2064 (0.1%)		1/2062 (0%)
SLEEP DISORDER	0/2064 (0%)		1/2062 (0%)
DRUG DEPENDENCE	1/2064 (0%)		1/2062 (0%)
SUICIDE ATTEMPT	3/2064 (0.1%)		0/2062 (0%)
COMPLETED SUICIDE	1/2064 (0%)		1/2062 (0%)
CONFUSIONAL STATE	7/2064 (0.3%)		3/2062 (0.1%)
ABNORMAL BEHAVIOUR	1/2064 (0%)		0/2062 (0%)
DYSTHYMIC DISORDER	1/2064 (0%)		0/2062 (0%)
ADJUSTMENT DISORDER	0/2064 (0%)		1/2062 (0%)
PERSONALITY DISORDER	1/2064 (0%)		0/2062 (0%)
MENTAL STATUS CHANGES	0/2064 (0%)		1/2062 (0%)
SOCIAL AVOIDANT BEHAVIOUR	0/2064 (0%)		1/2062 (0%)
ALCOHOL WITHDRAWAL SYNDROME	0/2064 (0%)		1/2062 (0%)
OBSESSIVE-COMPULSIVE DISORDER	1/2064 (0%)		0/2062 (0%)
Renal and urinary disorders
AZOTAEMIA	2/2064 (0.1%)		1/2062 (0%)
NEPHRITIS	0/2064 (0%)		1/2062 (0%)
HAEMATURIA	7/2064 (0.3%)		9/2062 (0.4%)
RENAL CYST	2/2064 (0.1%)		1/2062 (0%)
RENAL MASS	0/2064 (0%)		1/2062 (0%)
NEPHROPATHY	1/2064 (0%)		0/2062 (0%)
RENAL COLIC	0/2064 (0%)		2/2062 (0.1%)
BLADDER MASS	0/2064 (0%)		1/2062 (0%)
RENAL FAILURE	32/2064 (1.6%)		30/2062 (1.5%)
HYDRONEPHROSIS	1/2064 (0%)		2/2062 (0.1%)
RENAL ANEURYSM	0/2064 (0%)		1/2062 (0%)
NEPHROLITHIASIS	2/2064 (0.1%)		5/2062 (0.2%)
NEPHROSCLEROSIS	2/2064 (0.1%)		0/2062 (0%)
BLADDER PROLAPSE	1/2064 (0%)		0/2062 (0%)
CALCULUS BLADDER	1/2064 (0%)		0/2062 (0%)
CALCULUS URINARY	0/2064 (0%)		1/2062 (0%)
RENAL IMPAIRMENT	6/2064 (0.3%)		5/2062 (0.2%)
CALCULUS URETERIC	0/2064 (0%)		3/2062 (0.1%)
NEPHROPATHY TOXIC	1/2064 (0%)		0/2062 (0%)
URINARY RETENTION	3/2064 (0.1%)		5/2062 (0.2%)
NEPHROTIC SYNDROME	2/2064 (0.1%)		0/2062 (0%)
RENAL FAILURE ACUTE	21/2064 (1%)		10/2062 (0.5%)
URETERIC OBSTRUCTION	1/2064 (0%)		0/2062 (0%)
URINARY INCONTINENCE	2/2064 (0.1%)		0/2062 (0%)
CYSTITIS HAEMORRHAGIC	0/2064 (0%)		2/2062 (0.1%)
RENAL ARTERY STENOSIS	4/2064 (0.2%)		4/2062 (0.2%)
RENAL FAILURE CHRONIC	3/2064 (0.1%)		2/2062 (0.1%)
URINARY BLADDER POLYP	1/2064 (0%)		0/2062 (0%)
ACUTE PRERENAL FAILURE	1/2064 (0%)		0/2062 (0%)
RENAL TUBULAR NECROSIS	1/2064 (0%)		0/2062 (0%)
RENAL ARTERY THROMBOSIS	1/2064 (0%)		0/2062 (0%)
BLADDER NECK OBSTRUCTION	1/2064 (0%)		0/2062 (0%)
URINARY TRACT OBSTRUCTION	0/2064 (0%)		1/2062 (0%)
GLOMERULONEPHRITIS CHRONIC	0/2064 (0%)		1/2062 (0%)
Reproductive system and breast disorders
COLPOCELE	0/2064 (0%)		1/2062 (0%)
CYSTOCELE	0/2064 (0%)		1/2062 (0%)
RECTOCELE	0/2064 (0%)		2/2062 (0.1%)
PROSTATISM	1/2064 (0%)		0/2062 (0%)
BREAST MASS	2/2064 (0.1%)		0/2062 (0%)
PROSTATITIS	1/2064 (0%)		1/2062 (0%)
METRORRHAGIA	0/2064 (0%)		3/2062 (0.1%)
OVARIAN CYST	1/2064 (0%)		0/2062 (0%)
UTERINE POLYP	0/2064 (0%)		2/2062 (0.1%)
CERVIX DISORDER	0/2064 (0%)		1/2062 (0%)
GENITAL PROLAPSE	1/2064 (0%)		0/2062 (0%)
UTERINE DISORDER	0/2064 (0%)		1/2062 (0%)
UTERINE PROLAPSE	2/2064 (0.1%)		1/2062 (0%)
VAGINAL PROLAPSE	1/2064 (0%)		1/2062 (0%)
PROSTATIC DISORDER	0/2064 (0%)		1/2062 (0%)
ERECTILE DYSFUNCTION	0/2064 (0%)		1/2062 (0%)
ENDOMETRIAL HYPERPLASIA	1/2064 (0%)		1/2062 (0%)
UTERINE CERVIX STENOSIS	0/2064 (0%)		1/2062 (0%)
BENIGN PROSTATIC HYPERPLASIA	5/2064 (0.2%)		4/2062 (0.2%)
Respiratory, thoracic and mediastinal disorders
COUGH	1/2064 (0%)		2/2062 (0.1%)
APNOEA	1/2064 (0%)		0/2062 (0%)
ASTHMA	3/2064 (0.1%)		4/2062 (0.2%)
HYPOXIA	0/2064 (0%)		3/2062 (0.1%)
DYSPNOEA	65/2064 (3.1%)		72/2062 (3.5%)
PLEURISY	1/2064 (0%)		0/2062 (0%)
EMPHYSEMA	0/2064 (0%)		1/2062 (0%)
EPISTAXIS	3/2064 (0.1%)		4/2062 (0.2%)
ASPIRATION	2/2064 (0.1%)		0/2062 (0%)
ORTHOPNOEA	0/2064 (0%)		1/2062 (0%)
ATELECTASIS	1/2064 (0%)		0/2062 (0%)
HAEMOPTYSIS	5/2064 (0.2%)		0/2062 (0%)
HAEMOTHORAX	2/2064 (0.1%)		1/2062 (0%)
HYDROTHORAX	2/2064 (0.1%)		0/2062 (0%)
HYPERCAPNIA	1/2064 (0%)		1/2062 (0%)
PNEUMONITIS	0/2064 (0%)		1/2062 (0%)
BRONCHOSPASM	2/2064 (0.1%)		1/2062 (0%)
PNEUMOTHORAX	1/2064 (0%)		2/2062 (0.1%)
LUNG DISORDER	4/2064 (0.2%)		3/2062 (0.1%)
HYPOVENTILATION	1/2064 (0%)		1/2062 (0%)
ASTHMATIC CRISIS	1/2064 (0%)		0/2062 (0%)
DYSPNOEA AT REST	4/2064 (0.2%)		0/2062 (0%)
PLEURAL EFFUSION	8/2064 (0.4%)		5/2062 (0.2%)
PULMONARY OEDEMA	15/2064 (0.7%)		25/2062 (1.2%)
LUNG INFILTRATION	2/2064 (0.1%)		0/2062 (0%)
BRONCHITIS CHRONIC	4/2064 (0.2%)		2/2062 (0.1%)
BRONCHOPNEUMOPATHY	1/2064 (0%)		0/2062 (0%)
NOCTURNAL DYSPNOEA	1/2064 (0%)		0/2062 (0%)
PULMONARY EMBOLISM	20/2064 (1%)		27/2062 (1.3%)
PULMONARY FIBROSIS	1/2064 (0%)		2/2062 (0.1%)
RESPIRATORY ARREST	2/2064 (0.1%)		2/2062 (0.1%)
DYSPNOEA EXERTIONAL	5/2064 (0.2%)		2/2062 (0.1%)
PLEURAL HAEMORRHAGE	1/2064 (0%)		0/2062 (0%)
RESPIRATORY FAILURE	9/2064 (0.4%)		15/2062 (0.7%)
PNEUMONIA ASPIRATION	0/2064 (0%)		2/2062 (0.1%)
PULMONARY CONGESTION	0/2064 (0%)		1/2062 (0%)
PULMONARY HILUM MASS	0/2064 (0%)		1/2062 (0%)
RESPIRATORY ACIDOSIS	1/2064 (0%)		0/2062 (0%)
RESPIRATORY DISORDER	1/2064 (0%)		0/2062 (0%)
RESPIRATORY DISTRESS	1/2064 (0%)		2/2062 (0.1%)
BRONCHIAL OBSTRUCTION	1/2064 (0%)		0/2062 (0%)
PULMONARY AMYLOIDOSIS	0/2064 (0%)		1/2062 (0%)
PULMONARY HAEMORRHAGE	2/2064 (0.1%)		0/2062 (0%)
SLEEP APNOEA SYNDROME	1/2064 (0%)		1/2062 (0%)
ACUTE PULMONARY OEDEMA	9/2064 (0.4%)		12/2062 (0.6%)
NASAL SEPTUM DEVIATION	1/2064 (0%)		0/2062 (0%)
PULMONARY HYPERTENSION	1/2064 (0%)		5/2062 (0.2%)
ACUTE RESPIRATORY FAILURE	0/2064 (0%)		2/2062 (0.1%)
CHEYNE-STOKES RESPIRATION	1/2064 (0%)		0/2062 (0%)
INTERSTITIAL LUNG DISEASE	1/2064 (0%)		1/2062 (0%)
PULMONARY ARTERY THROMBOSIS	0/2064 (0%)		1/2062 (0%)
OBSTRUCTIVE AIRWAYS DISORDER	3/2064 (0.1%)		0/2062 (0%)
PULMONARY ARTERIAL HYPERTENSION	1/2064 (0%)		0/2062 (0%)
ACUTE RESPIRATORY DISTRESS SYNDROME	1/2064 (0%)		1/2062 (0%)
CHRONIC OBSTRUCTIVE PULMONARY DISEASE	21/2064 (1%)		23/2062 (1.1%)
Skin and subcutaneous tissue disorders
RASH	1/2064 (0%)		1/2062 (0%)
ECZEMA	0/2064 (0%)		1/2062 (0%)
DRY SKIN	0/2064 (0%)		1/2062 (0%)
PSORIASIS	0/2064 (0%)		1/2062 (0%)
ANGIOEDEMA	0/2064 (0%)		1/2062 (0%)
INTERTRIGO	0/2064 (0%)		1/2062 (0%)
SKIN ULCER	4/2064 (0.2%)		5/2062 (0.2%)
SKIN LESION	0/2064 (0%)		1/2062 (0%)
DRY GANGRENE	0/2064 (0%)		1/2062 (0%)
HYPERHIDROSIS	1/2064 (0%)		1/2062 (0%)
PARAPSORIASIS	0/2064 (0%)		1/2062 (0%)
SKIN NECROSIS	0/2064 (0%)		3/2062 (0.1%)
DIABETIC ULCER	0/2064 (0%)		1/2062 (0%)
ERYTHEMA NODOSUM	0/2064 (0%)		1/2062 (0%)
HYPOAESTHESIA FACIAL	1/2064 (0%)		0/2062 (0%)
LIPODYSTROPHY ACQUIRED	0/2064 (0%)		1/2062 (0%)
HAEMORRHAGE SUBCUTANEOUS	1/2064 (0%)		0/2062 (0%)
LEUKOCYTOCLASTIC VASCULITIS	1/2064 (0%)		1/2062 (0%)
Surgical and medical procedures
HOSPITALISATION	1/2064 (0%)		1/2062 (0%)
CORONARY ARTERY BYPASS	1/2064 (0%)		0/2062 (0%)
ARTERIOVENOUS SHUNT OPERATION	1/2064 (0%)		0/2062 (0%)
CARDIAC PACEMAKER REPLACEMENT	0/2064 (0%)		1/2062 (0%)
Vascular disorders
SHOCK	1/2064 (0%)		2/2062 (0.1%)
EMBOLISM	2/2064 (0.1%)		2/2062 (0.1%)
ARTERITIS	0/2064 (0%)		1/2062 (0%)
HAEMATOMA	6/2064 (0.3%)		3/2062 (0.1%)
ISCHAEMIA	1/2064 (0%)		6/2062 (0.3%)
PHLEBITIS	1/2064 (0%)		2/2062 (0.1%)
INFARCTION	1/2064 (0%)		0/2062 (0%)
THROMBOSIS	2/2064 (0.1%)		2/2062 (0.1%)
HAEMORRHAGE	2/2064 (0.1%)		1/2062 (0%)
HYPOTENSION	25/2064 (1.2%)		20/2062 (1%)
HYPERTENSION	33/2064 (1.6%)		35/2062 (1.7%)
VARICOSE VEIN	2/2064 (0.1%)		4/2062 (0.2%)
ANGIOSCLEROSIS	1/2064 (0%)		0/2062 (0%)
AORTIC ANEURYSM	4/2064 (0.2%)		3/2062 (0.1%)
AORTIC STENOSIS	5/2064 (0.2%)		5/2062 (0.2%)
ARTERIAL RUPTURE	0/2064 (0%)		1/2062 (0%)
ARTERIOSCLEROSIS	3/2064 (0.1%)		1/2062 (0%)
THROMBOPHLEBITIS	1/2064 (0%)		1/2062 (0%)
ANEURYSM RUPTURED	0/2064 (0%)		2/2062 (0.1%)
VENOUS THROMBOSIS	1/2064 (0%)		2/2062 (0.1%)
EXTREMITY NECROSIS	1/2064 (0%)		0/2062 (0%)
HYPOVOLAEMIC SHOCK	1/2064 (0%)		3/2062 (0.1%)
SHOCK HAEMORRHAGIC	1/2064 (0%)		0/2062 (0%)
TEMPORAL ARTERITIS	0/2064 (0%)		1/2062 (0%)
HYPERTENSIVE CRISIS	10/2064 (0.5%)		8/2062 (0.4%)
PERIPHERAL EMBOLISM	5/2064 (0.2%)		2/2062 (0.1%)
VARICOSE ULCERATION	1/2064 (0%)		0/2062 (0%)
ARTERIAL HAEMORRHAGE	0/2064 (0%)		1/2062 (0%)
CIRCULATORY COLLAPSE	7/2064 (0.3%)		4/2062 (0.2%)
DEEP VEIN THROMBOSIS	4/2064 (0.2%)		3/2062 (0.1%)
PERIPHERAL ISCHAEMIA	7/2064 (0.3%)		4/2062 (0.2%)
ILIAC ARTERY STENOSIS	1/2064 (0%)		1/2062 (0%)
ARTERIAL INSUFFICIENCY	0/2064 (0%)		1/2062 (0%)
ARTERIAL STENOSIS LIMB	0/2064 (0%)		3/2062 (0.1%)
ESSENTIAL HYPERTENSION	0/2064 (0%)		1/2062 (0%)
HYPERTENSIVE EMERGENCY	1/2064 (0%)		0/2062 (0%)
VASCULAR INSUFFICIENCY	2/2064 (0.1%)		0/2062 (0%)
VENOUS THROMBOSIS LIMB	1/2064 (0%)		0/2062 (0%)
AORTIC ANEURYSM RUPTURE	1/2064 (0%)		0/2062 (0%)
ORTHOSTATIC HYPOTENSION	3/2064 (0.1%)		4/2062 (0.2%)
VASCULAR PSEUDOANEURYSM	0/2064 (0%)		1/2062 (0%)
ARTERIAL THROMBOSIS LIMB	1/2064 (0%)		1/2062 (0%)
FEMORAL ARTERY OCCLUSION	4/2064 (0.2%)		1/2062 (0%)
FEMORAL ARTERIAL STENOSIS	0/2064 (0%)		1/2062 (0%)
INTERMITTENT CLAUDICATION	5/2064 (0.2%)		4/2062 (0.2%)
ARTERIAL OCCLUSIVE DISEASE	2/2064 (0.1%)		1/2062 (0%)
DIABETIC VASCULAR DISORDER	0/2064 (0%)		1/2062 (0%)
ARTERIOSCLEROSIS OBLITERANS	2/2064 (0.1%)		3/2062 (0.1%)
VISCERAL ARTERIAL ISCHAEMIA	0/2064 (0%)		1/2062 (0%)
CARDIOVASCULAR INSUFFICIENCY	0/2064 (0%)		1/2062 (0%)
PERIPHERAL VASCULAR DISORDER	5/2064 (0.2%)		3/2062 (0.1%)
THROMBOPHLEBITIS SUPERFICIAL	0/2064 (0%)		1/2062 (0%)
PERIPHERAL ARTERIAL OCCLUSIVE DISEASE	0/2064 (0%)		2/2062 (0.1%)
Other (Not Including Serious) Adverse Events
	IRBESARTAN		PLACEBO
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1255/2064 (60.8%)		1191/2062 (57.8%)
Cardiac disorders
CARDIAC FAILURE	133/2064 (6.4%)		134/2062 (6.5%)
ATRIAL FIBRILLATION	108/2064 (5.2%)		110/2062 (5.3%)
Gastrointestinal disorders
DIARRHOEA	127/2064 (6.2%)		89/2062 (4.3%)
General disorders
FATIGUE	108/2064 (5.2%)		96/2062 (4.7%)
CHEST PAIN	150/2064 (7.3%)		136/2062 (6.6%)
OEDEMA PERIPHERAL	204/2064 (9.9%)		205/2062 (9.9%)
Infections and infestations
INFLUENZA	124/2064 (6%)		111/2062 (5.4%)
BRONCHITIS	176/2064 (8.5%)		205/2062 (9.9%)
NASOPHARYNGITIS	180/2064 (8.7%)		174/2062 (8.4%)
Musculoskeletal and connective tissue disorders
BACK PAIN	132/2064 (6.4%)		117/2062 (5.7%)
ARTHRALGIA	108/2064 (5.2%)		104/2062 (5%)
Nervous system disorders
HEADACHE	126/2064 (6.1%)		138/2062 (6.7%)
DIZZINESS	262/2064 (12.7%)		253/2062 (12.3%)
Respiratory, thoracic and mediastinal disorders
COUGH	99/2064 (4.8%)		117/2062 (5.7%)
DYSPNOEA	177/2064 (8.6%)		217/2062 (10.5%)
Vascular disorders
HYPOTENSION	203/2064 (9.8%)		93/2062 (4.5%)
HYPERTENSION	202/2064 (9.8%)		252/2062 (12.2%)

Limitations/Caveats

[Not Specified]

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Certain Agreements

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

Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.