Trial Outcomes & Findings for Blopress Tablets Specified Drug-use Survey "Hypertension: Survey on Patients With Metabolic Syndrome" (NCT NCT02166697)

NCT ID: NCT02166697

Last Updated: 2016-09-28

Results Overview

ADR are defined as adverse events (AEs) which are in the investigator's opinion of causal relationship to the study treatment. AEs are defined as any unfavorable and unintended signs, symptoms or diseases temporally associated with the use of a medicinal product reported from the first dose of study drug to the last dose of study drug.

• Recruitment status: COMPLETED
• Target enrollment: 14151 participants
• Primary outcome timeframe: Baseline up to 3 years
• Results posted on: 2016-09-28

Participant Flow

Participants took part in the study at 1,126 investigative sites in Japan from 7 June 2006 to 30 November 2010.

Participants with a historical diagnosis of hypertension with metabolic syndrome-related risk factors were observed in a single treatment group to receive candesartan cilexetil 4 milligrams (mg).

Participant milestones

Measure	Candesartan Cilexetil Candesartan cilexetil 4 mg, tablet, orally, once daily for up to 3 years.
Overall Study STARTED	14151
Overall Study COMPLETED	13804
Overall Study NOT COMPLETED	347

Reasons for withdrawal

Measure	Candesartan Cilexetil Candesartan cilexetil 4 mg, tablet, orally, once daily for up to 3 years.
Overall Study Protocol Violation	347

Baseline Characteristics

Blopress Tablets Specified Drug-use Survey "Hypertension: Survey on Patients With Metabolic Syndrome"

Baseline characteristics by cohort

Measure	Candesartan Cilexetil n=13804 Participants Candesartan cilexetil 4 mg, tablet, orally, once daily for up to 3 years.
Age, Continuous	60.5 Years STANDARD_DEVIATION 9.8 • n=5 Participants
Sex: Female, Male Female	6087 Participants n=5 Participants
Sex: Female, Male Male	7717 Participants n=5 Participants
Initial Daily Dose of Blopress Less than (<) 4 mg	214 Participants n=5 Participants
Initial Daily Dose of Blopress 4 mg	3934 Participants n=5 Participants
Initial Daily Dose of Blopress 6 mg	38 Participants n=5 Participants
Initial Daily Dose of Blopress 8 mg	8505 Participants n=5 Participants
Initial Daily Dose of Blopress 10 mg	1 Participants n=5 Participants
Initial Daily Dose of Blopress 12 mg	1104 Participants n=5 Participants
Initial Daily Dose of Blopress Greater than (>) 12 mg	8 Participants n=5 Participants
Blood Pressure Systolic Blood Pressure	156.2 Millimeter of mercury (mmHg) STANDARD_DEVIATION 17.9 • n=5 Participants
Blood Pressure Diastolic Blood Pressure	90.2 Millimeter of mercury (mmHg) STANDARD_DEVIATION 12.6 • n=5 Participants
Pulse Rate	73.9 Pulse per minute STANDARD_DEVIATION 10.7 • n=5 Participants
Height	160.28 Centimeter (cm) STANDARD_DEVIATION 9.42 • n=5 Participants
Weight	68.07 Kilogram (Kg) STANDARD_DEVIATION 12.84 • n=5 Participants
Body Mass Index	26.40 Kilogram per square meter (kg/m^2) STANDARD_DEVIATION 3.84 • n=5 Participants
Waist Circumference	90.56 cm STANDARD_DEVIATION 9.76 • n=5 Participants
Fasting Triglycerides	166.1 Milligrams per deciliter (mg/dL) STANDARD_DEVIATION 101.6 • n=5 Participants
High Density Lipoprotein (HDL) Cholesterol	55.0 mg/dL STANDARD_DEVIATION 15.2 • n=5 Participants
Fasting Blood Glucose	118.4 mg/dL STANDARD_DEVIATION 41.9 • n=5 Participants
Glycated Hemoglobin (HbA1c)	6.46 Hemoglobin Percent STANDARD_DEVIATION 1.36 • n=5 Participants
Total Cholesterol	212.1 mg/dL STANDARD_DEVIATION 37.7 • n=5 Participants
Serum Creatinine	0.76 mg/dL STANDARD_DEVIATION 0.29 • n=5 Participants
Urinary Protein 0 mg/dL	8365 Participants n=5 Participants
Urinary Protein 15-30mg/dL	1005 Participants n=5 Participants
Urinary Protein 30-300mg/dL	836 Participants n=5 Participants
Urinary Protein 100-300mg/dL	440 Participants n=5 Participants
Urinary Protein 300-1000mg/dL	185 Participants n=5 Participants
Urinary Protein Unknown	2973 Participants n=5 Participants
Urinary Sugar 0 mg/dL	8907 Participants n=5 Participants
Urinary Sugar 100 mg/dL	406 Participants n=5 Participants
Urinary Sugar 250 mg/dL	596 Participants n=5 Participants
Urinary Sugar 500 mg/dL	330 Participants n=5 Participants
Urinary Sugar 1000 mg/dL	566 Participants n=5 Participants
Urinary Sugar Unknown	2999 Participants n=5 Participants
Microalbumin in Urine	158.5 Milligram per day (mg/day) STANDARD_DEVIATION 653.6 • n=5 Participants
Insulin	11.09 mcU/mL STANDARD_DEVIATION 11.38 • n=5 Participants
Apoprotein A	145.4 mg/dL STANDARD_DEVIATION 24.5 • n=5 Participants
Apoprotein B	104.1 mg/dL STANDARD_DEVIATION 27.5 • n=5 Participants
Adiponectin	5.80 Microgram per milliliter (mcg/mL) STANDARD_DEVIATION 6.92 • n=5 Participants
Leptin	9.20 Nanogram per milliliter (ng/mL) STANDARD_DEVIATION 8.24 • n=5 Participants
Smoking Status Non Smoker	10823 Participants n=5 Participants
Smoking Status Smoker	2981 Participants n=5 Participants
Alcohol Consumption Alcohol Non-Consumer	8265 Participants n=5 Participants
Alcohol Consumption Alcohol Consumer	5539 Participants n=5 Participants
Predisposition to Hypersensitivity Had no Predisposition to Hypersensitivity	12259 Participants n=5 Participants
Predisposition to Hypersensitivity Had Predisposition to Hypersensitivity	691 Participants n=5 Participants
Predisposition to Hypersensitivity Unknown	854 Participants n=5 Participants
Medical History Did not Have Medical History	3833 Participants n=5 Participants
Medical History Have Medical History	9835 Participants n=5 Participants
Medical History Unknown	136 Participants n=5 Participants
Breakdown of Medical History Cerebral Infarction	593 Participants n=5 Participants
Breakdown of Medical History Cerebral Hemorrhage	63 Participants n=5 Participants
Breakdown of Medical History Subarachnoid Hemorrhage	22 Participants n=5 Participants
Breakdown of Medical History Myocardial Infarction	153 Participants n=5 Participants
Breakdown of Medical History Cardiac Failure	121 Participants n=5 Participants
Breakdown of Medical History Angina Pectoris	463 Participants n=5 Participants
Breakdown of Medical History Diabetes Mellitus	4755 Participants n=5 Participants
Breakdown of Medical History Hyperlipidemia	7841 Participants n=5 Participants
Breakdown of Medical History Other Cerebrovascular/Cardiovascular Diseases	615 Participants n=5 Participants
Breakdown of Medical History Diabetic Retinopathy	3 Participants n=5 Participants
Breakdown of Medical History Renal Dialysis	0 Participants n=5 Participants
Breakdown of Medical History Atrial fibrillation	257 Participants n=5 Participants
Consumption of Concomitant Antihypertensive Medications Had no Consumption	8006 Participants n=5 Participants
Consumption of Concomitant Antihypertensive Medications Had Consumption	5798 Participants n=5 Participants
Breakdown of Concomitant Antihypertensive Medications Diuretics	705 Participants n=5 Participants
Breakdown of Concomitant Antihypertensive Medications Alpha-Blockers	323 Participants n=5 Participants
Breakdown of Concomitant Antihypertensive Medications Alpha-Beta or Beta-Blockers	867 Participants n=5 Participants
Breakdown of Concomitant Antihypertensive Medications Calcium Blockers	4886 Participants n=5 Participants
Breakdown of Concomitant Antihypertensive Medications Angiotensin Converting Enzyme (ACE) Inhibitors	262 Participants n=5 Participants
Breakdown of Concomitant Antihypertensive Medications Angiotensin2ReceptorBlockers(other than Blopress)	131 Participants n=5 Participants
Breakdown of Concomitant Antihypertensive Medications Other	69 Participants n=5 Participants
Consumption of Concomitant Antidiabetic Medications Had no consumption	10494 Participants n=5 Participants
Consumption of Concomitant Antidiabetic Medications Had Consumption	3310 Participants n=5 Participants
Breakdown of Concomitant Antidiabetic Medications Alpha-Glucosidase Inhibitor	1127 Participants n=5 Participants
Breakdown of Concomitant Antidiabetic Medications Insulin Sensitizers	1077 Participants n=5 Participants
Breakdown of Concomitant Antidiabetic Medications Sulfonylurea Drugs	1728 Participants n=5 Participants
Breakdown of Concomitant Antidiabetic Medications Short Acting Insulin Secretagogues	306 Participants n=5 Participants
Breakdown of Concomitant Antidiabetic Medications Biguanides	686 Participants n=5 Participants
Breakdown of Concomitant Antidiabetic Medications Insulin	364 Participants n=5 Participants
Breakdown of Concomitant Antidiabetic Medications Other	44 Participants n=5 Participants
Consumption of Concomitant Antihyperlipidemic Drugs Had no Consumption	9112 Participants n=5 Participants
Consumption of Concomitant Antihyperlipidemic Drugs Had Consumption	4692 Participants n=5 Participants
Breakdown of Concomitant Antihyperlipidemic Drugs Statins	3784 Participants n=5 Participants
Breakdown of Concomitant Antihyperlipidemic Drugs Fibrates	730 Participants n=5 Participants
Breakdown of Concomitant Antihyperlipidemic Drugs Eicosapentaenoic Acid	230 Participants n=5 Participants
Breakdown of Concomitant Antihyperlipidemic Drugs Other	122 Participants n=5 Participants
Consumption of Other Concomitant Medications Had no Consumption	9110 Participants n=5 Participants
Consumption of Other Concomitant Medications Had Consumption	4694 Participants n=5 Participants
Breakdown of Other Concomitant Medication Antithrombotic Drugs	1322 Participants n=5 Participants
Breakdown of Other Concomitant Medication Antigout Drugs or Antihyperuricemic Drugs	903 Participants n=5 Participants
Breakdown of Other Concomitant Medication Other	3005 Participants n=5 Participants
Pulse Wave Velocity	1713.8 Centimeter per second (cm/s) STANDARD_DEVIATION 523.8 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline up to 3 years

Population: The safety analysis set was defined as all participants who were enrolled and completed the study.

ADR are defined as adverse events (AEs) which are in the investigator's opinion of causal relationship to the study treatment. AEs are defined as any unfavorable and unintended signs, symptoms or diseases temporally associated with the use of a medicinal product reported from the first dose of study drug to the last dose of study drug.

Outcome measures

Measure	Candesartan Cilexetil n=13804 Participants Candesartan cilexetil 4 mg, tablet, orally, once daily for up to 3 years.
Number of Participants Reporting One or More Adverse Drug Reactions (ADR)	230 Participants

PRIMARY outcome

Timeframe: Baseline up to 3 years

Population: The safety analysis set was defined as all participants who were enrolled and completed the study.

SADR are defined as serious adverse events (SAEs) which are in the investigator's opinion of causal relationship to the study treatment. SADR was an ADR resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.

Outcome measures

Measure	Candesartan Cilexetil n=13804 Participants Candesartan cilexetil 4 mg, tablet, orally, once daily for up to 3 years.
Number of Participants Reporting One or More Serious Adverse Drug Reactions (SADR)	320 Participants

SECONDARY outcome

Timeframe: Baseline up to 3 years

Population: The efficacy assessment population was defined as participants who completed the study and had efficacy data at baseline and post-baseline time points available.

Cerebrovascular/cardiovascular events reported to be associated with Blopress were reported. The composite events classified under primary major adverse cardiac Events (MACE) 1 and primary MACE2 were defined as: MACE1: sudden death, cerebral hemorrhage, cerebral infarction, subarachnoid hemorrhage, and acute myocardial infarction; MACE2: MACE1 + hospitalization for cardiac failure and intervention/hospitalization for angina pectoris. Renal events include (transition to dialysis + renal transplant).

Outcome measures

Measure	Candesartan Cilexetil n=13804 Participants Candesartan cilexetil 4 mg, tablet, orally, once daily for up to 3 years.
Incidence of Cerebrovascular/Cardiovascular Events Sudden Death	0.24 Number of events per 1,000 person-years
Incidence of Cerebrovascular/Cardiovascular Events Cerebral Hemorrhage	0.57 Number of events per 1,000 person-years
Incidence of Cerebrovascular/Cardiovascular Events Cerebral Infarction	2.34 Number of events per 1,000 person-years
Incidence of Cerebrovascular/Cardiovascular Events Subarachnoid Hemorrhage	0.15 Number of events per 1,000 person-years
Incidence of Cerebrovascular/Cardiovascular Events Acute Myocardial Infarction	0.99 Number of events per 1,000 person-years
Incidence of Cerebrovascular/Cardiovascular Events Hospitalization for Heart Failure	0.27 Number of events per 1,000 person-years
Incidence of Cerebrovascular/Cardiovascular Events Intervention/Hospitalization for Angina Pectoris	1.74 Number of events per 1,000 person-years
Incidence of Cerebrovascular/Cardiovascular Events Atrial Fibrillation	1.35 Number of events per 1,000 person-years
Incidence of Cerebrovascular/Cardiovascular Events Transition to Dialysis	0.30 Number of events per 1,000 person-years
Incidence of Cerebrovascular/Cardiovascular Events Renal Transplant	0.00 Number of events per 1,000 person-years
Incidence of Cerebrovascular/Cardiovascular Events Dissecting Aortic Aneurysm	0.06 Number of events per 1,000 person-years
Incidence of Cerebrovascular/Cardiovascular Events Diabetic Retinopathy	0.15 Number of events per 1,000 person-years
Incidence of Cerebrovascular/Cardiovascular Events New-Onset Diabetes	4.35 Number of events per 1,000 person-years
Incidence of Cerebrovascular/Cardiovascular Events Primary MACE	4.29 Number of events per 1,000 person-years
Incidence of Cerebrovascular/Cardiovascular Events Primary MACE 2	6.29 Number of events per 1,000 person-years
Incidence of Cerebrovascular/Cardiovascular Events Renal Events	0.30 Number of events per 1,000 person-years

SECONDARY outcome

Timeframe: Baseline up to 3 years

Population: The efficacy assessment population was defined as participants who completed the study and had efficacy data at baseline and post-baseline time points available.

Participants reporting cerebrovascular/cardiovascular events who had either obesity, blood glucose abnormalities, or lipid abnormalities as any one of the underlying risk factors associated with Blopress at the time of enrollment were reported.The composite events classified under primary MACE1 and primary MACE2 were defined as: MACE1: sudden death, cerebral hemorrhage, cerebral infarction, subarachnoid hemorrhage, and acute myocardial infarction; MACE2: MACE1 + hospitalization for cardiac failure and intervention/hospitalization for angina pectoris. Renal events include (transition to dialysis + renal transplant).

Outcome measures

Measure	Candesartan Cilexetil n=4056 Participants Candesartan cilexetil 4 mg, tablet, orally, once daily for up to 3 years.
Incidence of Cerebrovascular/Cardiovascular Events Affected by Underlying Risk Factors of Obesity, Blood Glucose Abnormalities, or Lipid Abnormalities Sudden Death	0.21 Number of events/1,000 person-years
Incidence of Cerebrovascular/Cardiovascular Events Affected by Underlying Risk Factors of Obesity, Blood Glucose Abnormalities, or Lipid Abnormalities Cerebral Hemorrhage	0.41 Number of events/1,000 person-years
Incidence of Cerebrovascular/Cardiovascular Events Affected by Underlying Risk Factors of Obesity, Blood Glucose Abnormalities, or Lipid Abnormalities Cerebral Infarction	1.55 Number of events/1,000 person-years
Incidence of Cerebrovascular/Cardiovascular Events Affected by Underlying Risk Factors of Obesity, Blood Glucose Abnormalities, or Lipid Abnormalities Subarachnoid Hemorrhage	0.10 Number of events/1,000 person-years
Incidence of Cerebrovascular/Cardiovascular Events Affected by Underlying Risk Factors of Obesity, Blood Glucose Abnormalities, or Lipid Abnormalities Acute Myocardial Infarction	0.62 Number of events/1,000 person-years
Incidence of Cerebrovascular/Cardiovascular Events Affected by Underlying Risk Factors of Obesity, Blood Glucose Abnormalities, or Lipid Abnormalities Hospitalization for Heart Failure	0.10 Number of events/1,000 person-years
Incidence of Cerebrovascular/Cardiovascular Events Affected by Underlying Risk Factors of Obesity, Blood Glucose Abnormalities, or Lipid Abnormalities Intervention/Hospitalization for Angina Pectoris	1.45 Number of events/1,000 person-years
Incidence of Cerebrovascular/Cardiovascular Events Affected by Underlying Risk Factors of Obesity, Blood Glucose Abnormalities, or Lipid Abnormalities Atrial Fibrillation	0.62 Number of events/1,000 person-years
Incidence of Cerebrovascular/Cardiovascular Events Affected by Underlying Risk Factors of Obesity, Blood Glucose Abnormalities, or Lipid Abnormalities Transition to Dialysis	0.31 Number of events/1,000 person-years
Incidence of Cerebrovascular/Cardiovascular Events Affected by Underlying Risk Factors of Obesity, Blood Glucose Abnormalities, or Lipid Abnormalities Renal Transplant	0.00 Number of events/1,000 person-years
Incidence of Cerebrovascular/Cardiovascular Events Affected by Underlying Risk Factors of Obesity, Blood Glucose Abnormalities, or Lipid Abnormalities Dissecting Aortic Aneurysm	0.00 Number of events/1,000 person-years
Incidence of Cerebrovascular/Cardiovascular Events Affected by Underlying Risk Factors of Obesity, Blood Glucose Abnormalities, or Lipid Abnormalities Diabetic Retinopathy	0.10 Number of events/1,000 person-years
Incidence of Cerebrovascular/Cardiovascular Events Affected by Underlying Risk Factors of Obesity, Blood Glucose Abnormalities, or Lipid Abnormalities New-Onset Diabetes	3.32 Number of events/1,000 person-years
Incidence of Cerebrovascular/Cardiovascular Events Affected by Underlying Risk Factors of Obesity, Blood Glucose Abnormalities, or Lipid Abnormalities Primary MACE	2.90 Number of events/1,000 person-years
Incidence of Cerebrovascular/Cardiovascular Events Affected by Underlying Risk Factors of Obesity, Blood Glucose Abnormalities, or Lipid Abnormalities Primary MACE 2	4.45 Number of events/1,000 person-years
Incidence of Cerebrovascular/Cardiovascular Events Affected by Underlying Risk Factors of Obesity, Blood Glucose Abnormalities, or Lipid Abnormalities Renal Events	0.31 Number of events/1,000 person-years

SECONDARY outcome

Timeframe: Baseline up to 3 years

Population: The efficacy assessment population was defined as participants who completed the study and had efficacy data at baseline and post-baseline time points available.

Participants reporting cerebrovascular/cardiovascular events who had multiple underlying risk factors which included either obesity + blood glucose abnormalities, obesity + lipid abnormalities OR blood glucose + lipid abnormalities associated with Blopress at the time of enrollment were reported. The composite events classified under primary MACE1 and primary MACE2 were defined as: MACE1: sudden death, cerebral hemorrhage, cerebral infarction, subarachnoid hemorrhage, and acute myocardial infarction; MACE2: MACE1 + hospitalization for cardiac failure and intervention/hospitalization for angina pectoris. Renal events include (transition to dialysis + renal transplant).

Outcome measures

Measure	Candesartan Cilexetil n=6216 Participants Candesartan cilexetil 4 mg, tablet, orally, once daily for up to 3 years.
Incidence of Cerebrovascular/Cardiovascular Events Affected by Underlying Risk Factors of Obesity + Blood Glucose Abnormalities, Obesity + Lipid Abnormalities, or Blood Glucose Abnormalities + Lipid Abnormalities Sudden Death	0.20 Number of events/1,000 person-years
Incidence of Cerebrovascular/Cardiovascular Events Affected by Underlying Risk Factors of Obesity + Blood Glucose Abnormalities, Obesity + Lipid Abnormalities, or Blood Glucose Abnormalities + Lipid Abnormalities Cerebral Hemorrhage	0.53 Number of events/1,000 person-years
Incidence of Cerebrovascular/Cardiovascular Events Affected by Underlying Risk Factors of Obesity + Blood Glucose Abnormalities, Obesity + Lipid Abnormalities, or Blood Glucose Abnormalities + Lipid Abnormalities Cerebral Infarction	2.19 Number of events/1,000 person-years
Incidence of Cerebrovascular/Cardiovascular Events Affected by Underlying Risk Factors of Obesity + Blood Glucose Abnormalities, Obesity + Lipid Abnormalities, or Blood Glucose Abnormalities + Lipid Abnormalities Subarachnoid Hemorrhage	0.13 Number of events/1,000 person-years
Incidence of Cerebrovascular/Cardiovascular Events Affected by Underlying Risk Factors of Obesity + Blood Glucose Abnormalities, Obesity + Lipid Abnormalities, or Blood Glucose Abnormalities + Lipid Abnormalities Acute Myocardial Infarction	1.06 Number of events/1,000 person-years
Incidence of Cerebrovascular/Cardiovascular Events Affected by Underlying Risk Factors of Obesity + Blood Glucose Abnormalities, Obesity + Lipid Abnormalities, or Blood Glucose Abnormalities + Lipid Abnormalities Hospitalization for heart Failure	0.33 Number of events/1,000 person-years
Incidence of Cerebrovascular/Cardiovascular Events Affected by Underlying Risk Factors of Obesity + Blood Glucose Abnormalities, Obesity + Lipid Abnormalities, or Blood Glucose Abnormalities + Lipid Abnormalities Intervention/Hospitalization for Angina Pectoris	1.33 Number of events/1,000 person-years
Incidence of Cerebrovascular/Cardiovascular Events Affected by Underlying Risk Factors of Obesity + Blood Glucose Abnormalities, Obesity + Lipid Abnormalities, or Blood Glucose Abnormalities + Lipid Abnormalities Atrial Fibrillation	1.46 Number of events/1,000 person-years
Incidence of Cerebrovascular/Cardiovascular Events Affected by Underlying Risk Factors of Obesity + Blood Glucose Abnormalities, Obesity + Lipid Abnormalities, or Blood Glucose Abnormalities + Lipid Abnormalities Transition to Dialysis	0.07 Number of events/1,000 person-years
Incidence of Cerebrovascular/Cardiovascular Events Affected by Underlying Risk Factors of Obesity + Blood Glucose Abnormalities, Obesity + Lipid Abnormalities, or Blood Glucose Abnormalities + Lipid Abnormalities Renal Transplant	0.00 Number of events/1,000 person-years
Incidence of Cerebrovascular/Cardiovascular Events Affected by Underlying Risk Factors of Obesity + Blood Glucose Abnormalities, Obesity + Lipid Abnormalities, or Blood Glucose Abnormalities + Lipid Abnormalities Dissecting Aortic Aneurysm	0.07 Number of events/1,000 person-years
Incidence of Cerebrovascular/Cardiovascular Events Affected by Underlying Risk Factors of Obesity + Blood Glucose Abnormalities, Obesity + Lipid Abnormalities, or Blood Glucose Abnormalities + Lipid Abnormalities Diabetic Retinopathy	0.07 Number of events/1,000 person-years
Incidence of Cerebrovascular/Cardiovascular Events Affected by Underlying Risk Factors of Obesity + Blood Glucose Abnormalities, Obesity + Lipid Abnormalities, or Blood Glucose Abnormalities + Lipid Abnormalities New-Onset Diabetes	4.51 Number of events/1,000 person-years
Incidence of Cerebrovascular/Cardiovascular Events Affected by Underlying Risk Factors of Obesity + Blood Glucose Abnormalities, Obesity + Lipid Abnormalities, or Blood Glucose Abnormalities + Lipid Abnormalities Primary MACE	4.11 Number of events/1,000 person-years
Incidence of Cerebrovascular/Cardiovascular Events Affected by Underlying Risk Factors of Obesity + Blood Glucose Abnormalities, Obesity + Lipid Abnormalities, or Blood Glucose Abnormalities + Lipid Abnormalities Primary MACE 2	5.77 Number of events/1,000 person-years
Incidence of Cerebrovascular/Cardiovascular Events Affected by Underlying Risk Factors of Obesity + Blood Glucose Abnormalities, Obesity + Lipid Abnormalities, or Blood Glucose Abnormalities + Lipid Abnormalities Renal Events	0.07 Number of events/1,000 person-years

SECONDARY outcome

Timeframe: Baseline up to 3 years

Population: The efficacy assessment population was defined as participants who completed the study and had efficacy data at baseline and post-baseline time points available.

Participants reporting cerebrovascular/cardiovascular events who had obesity, blood glucose and lipid abnormalities associated with Blopress at the time of enrollment were reported. The composite events classified under primary MACE1 and primary MACE2 were defined as: MACE1: sudden death, cerebral hemorrhage, cerebral infarction, subarachnoid hemorrhage, and acute myocardial infarction; MACE2: MACE1 + hospitalization for cardiac failure and intervention/hospitalization for angina pectoris. Renal events include (transition to dialysis + renal transplant).

Outcome measures

Measure	Candesartan Cilexetil n=3582 Participants Candesartan cilexetil 4 mg, tablet, orally, once daily for up to 3 years.
Incidence of Cerebrovascular/Cardiovascular Events Affected by Underlying Risk Factors of Obesity + Blood Glucose Abnormalities + Lipid Abnormalities Sudden Death	0.35 Number of events/1,000 person-years
Incidence of Cerebrovascular/Cardiovascular Events Affected by Underlying Risk Factors of Obesity + Blood Glucose Abnormalities + Lipid Abnormalities Cerebral Hemorrhage	0.81 Number of events/1,000 person-years
Incidence of Cerebrovascular/Cardiovascular Events Affected by Underlying Risk Factors of Obesity + Blood Glucose Abnormalities + Lipid Abnormalities Cerebral Infarction	3.48 Number of events/1,000 person-years
Incidence of Cerebrovascular/Cardiovascular Events Affected by Underlying Risk Factors of Obesity + Blood Glucose Abnormalities + Lipid Abnormalities Subarachnoid Hemorrhage	0.23 Number of events/1,000 person-years
Incidence of Cerebrovascular/Cardiovascular Events Affected by Underlying Risk Factors of Obesity + Blood Glucose Abnormalities + Lipid Abnormalities Acute Myocardial Infarction	1.28 Number of events/1,000 person-years
Incidence of Cerebrovascular/Cardiovascular Events Affected by Underlying Risk Factors of Obesity + Blood Glucose Abnormalities + Lipid Abnormalities Hospitalization for Heart Failure	0.35 Number of events/1,000 person-years
Incidence of Cerebrovascular/Cardiovascular Events Affected by Underlying Risk Factors of Obesity + Blood Glucose Abnormalities + Lipid Abnormalities Intervention/Hospitalization for Angina Pectoris	2.78 Number of events/1,000 person-years
Incidence of Cerebrovascular/Cardiovascular Events Affected by Underlying Risk Factors of Obesity + Blood Glucose Abnormalities + Lipid Abnormalities Atrial Fibrillation	1.97 Number of events/1,000 person-years
Incidence of Cerebrovascular/Cardiovascular Events Affected by Underlying Risk Factors of Obesity + Blood Glucose Abnormalities + Lipid Abnormalities Transition to Dialysis	0.70 Number of events/1,000 person-years
Incidence of Cerebrovascular/Cardiovascular Events Affected by Underlying Risk Factors of Obesity + Blood Glucose Abnormalities + Lipid Abnormalities Renal Transplant	0.00 Number of events/1,000 person-years
Incidence of Cerebrovascular/Cardiovascular Events Affected by Underlying Risk Factors of Obesity + Blood Glucose Abnormalities + Lipid Abnormalities Dissecting Aortic Aneurysm	0.12 Number of events/1,000 person-years
Incidence of Cerebrovascular/Cardiovascular Events Affected by Underlying Risk Factors of Obesity + Blood Glucose Abnormalities + Lipid Abnormalities Diabetic Retinopathy	0.35 Number of events/1,000 person-years
Incidence of Cerebrovascular/Cardiovascular Events Affected by Underlying Risk Factors of Obesity + Blood Glucose Abnormalities + Lipid Abnormalities New-Onset Diabetes	5.22 Number of events/1,000 person-years
Incidence of Cerebrovascular/Cardiovascular Events Affected by Underlying Risk Factors of Obesity + Blood Glucose Abnormalities + Lipid Abnormalities Primary MACE	6.14 Number of events/1,000 person-years
Incidence of Cerebrovascular/Cardiovascular Events Affected by Underlying Risk Factors of Obesity + Blood Glucose Abnormalities + Lipid Abnormalities Primary MACE 2	9.27 Number of events/1,000 person-years
Incidence of Cerebrovascular/Cardiovascular Events Affected by Underlying Risk Factors of Obesity + Blood Glucose Abnormalities + Lipid Abnormalities Renal Events	0.70 Number of events/1,000 person-years

Adverse Events

Candesartan Cilexetil

Serious events: 320 serious events

Other events: 230 other events

Deaths: 0 deaths

Serious adverse events

Measure	Candesartan Cilexetil n=13804 participants at risk Candesartan cilexetil 4 mg, tablet, orally, once daily for up to 3 years.
Blood and lymphatic system disorders Anaemia	0.01% 2/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Blood and lymphatic system disorders Aplastic anaemia	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Blood and lymphatic system disorders Disseminated intravascular coagulation	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Cardiac disorders Acute myocardial infarction	0.23% 32/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Cardiac disorders Angina pectoris	0.38% 53/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Cardiac disorders Atrial fibrillation	0.05% 7/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Cardiac disorders Atrial flutter	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Cardiac disorders Bradycardia	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Cardiac disorders Cardiac failure	0.07% 9/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Cardiac disorders Cardio-respiratory arrest	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Cardiac disorders Sick sinus syndrome	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Ear and labyrinth disorders Meniere's disease	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Endocrine disorders Goitre	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Eye disorders Blindness unilateral	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Eye disorders Diabetic retinopathy	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Eye disorders Retinal artery occlusion	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Abdominal pain	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Duodenal ulcer	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Duodenal ulcer haemorrhage	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Gastric ulcer	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Inguinal hernia	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Intestinal obstruction	0.02% 3/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Nausea	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Oesophageal varices haemorrhage	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Pancreatitis	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Pancreatitis acute	0.01% 2/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Small intestinal haemorrhage	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
General disorders Death	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
General disorders Multi-organ failure	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
General disorders Oedema	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
General disorders Sudden death	0.06% 8/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
General disorders Non-cardiac chest pain	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Hepatobiliary disorders Bile duct stone	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Hepatobiliary disorders Cholangitis	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Hepatobiliary disorders Cholecystitis	0.01% 2/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Hepatobiliary disorders Cholelithiasis	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Hepatobiliary disorders Jaundice	0.01% 2/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Hepatobiliary disorders Hepatic ischaemia	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Immune system disorders Anaphylactic shock	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Cellulitis	0.01% 2/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Cholangitis suppurative	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Pneumonia	0.04% 5/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Sepsis	0.01% 2/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Injury, poisoning and procedural complications Accident	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Injury, poisoning and procedural complications Cerebral haemorrhage traumatic	0.01% 2/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Injury, poisoning and procedural complications Fall	0.01% 2/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Injury, poisoning and procedural complications Femoral neck fracture	0.02% 3/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Injury, poisoning and procedural complications Pneumoconiosis	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Injury, poisoning and procedural complications Road traffic accident	0.04% 5/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Injury, poisoning and procedural complications Spinal compression fracture	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Injury, poisoning and procedural complications Stress fracture	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Injury, poisoning and procedural complications Subdural haematoma	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Injury, poisoning and procedural complications Excoriation	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Injury, poisoning and procedural complications Contusion	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Investigations Alanine aminotransferase increased	0.01% 2/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Investigations Aspartate aminotransferase increased	0.01% 2/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Investigations Blood creatinine abnormal	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Investigations Blood creatinine increased	0.04% 5/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Investigations Blood glucose decreased	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Investigations Blood glucose increased	0.02% 3/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Investigations Blood potassium increased	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Investigations Blood pressure increased	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Investigations Blood triglycerides increased	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Investigations Blood urea increased	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Investigations Glucose urine present	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Investigations Glycosylated haemoglobin increased	0.02% 3/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Investigations Haemoglobin decreased	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Metabolism and nutrition disorders Diabetes mellitus	0.02% 3/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Metabolism and nutrition disorders Hypoglycaemia	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Metabolism and nutrition disorders Marasmus	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Musculoskeletal and connective tissue disorders Back pain	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Musculoskeletal and connective tissue disorders Collagen disorder	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Musculoskeletal and connective tissue disorders Lumbar spinal stenosis	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Musculoskeletal and connective tissue disorders Osteonecrosis	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Musculoskeletal and connective tissue disorders Spinal column stenosis	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenoma benign	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder cancer	0.01% 2/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder cancer recurrent	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder neoplasm	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.01% 2/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon cancer	0.01% 2/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gallbladder cancer	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastric cancer	0.07% 9/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastric cancer recurrent	0.01% 2/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hepatic neoplasm	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hepatic neoplasm malignant	0.02% 3/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Laryngeal cancer	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to lymph nodes	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Oesophageal carcinoma	0.01% 2/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pancreatic carcinoma	0.02% 3/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pituitary tumour	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Rectal cancer	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Renal cancer	0.01% 2/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Renal cancer recurrent	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine cancer	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hepatic cancer metastatic	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm malignant	0.04% 5/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Large intestine carcinoma	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to central nervous system	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	0.02% 3/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Renal neoplasm	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders Cerebral haemorrhage	0.14% 20/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders Cerebral infarction	0.44% 61/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders Dementia	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders Depressed level of consciousness	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders Dizziness	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders Mental impairment	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders Subarachnoid haemorrhage	0.03% 4/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders Transient ischaemic attack	0.03% 4/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Psychiatric disorders Completed suicide	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Renal and urinary disorders Azotaemia	0.01% 2/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Renal and urinary disorders Calculus urinary	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Renal and urinary disorders Hydronephrosis	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Renal and urinary disorders Post streptococcal glomerulonephritis	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Renal and urinary disorders Renal artery stenosis	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Renal and urinary disorders Renal failure	0.07% 10/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Respiratory, thoracic and mediastinal disorders Sleep apnoea syndrome	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Respiratory, thoracic and mediastinal disorders Status asthmaticus	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Skin and subcutaneous tissue disorders Henoch-Schonlein purpura	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Surgical and medical procedures Spinal operation	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Surgical and medical procedures Cataract operation	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Vascular disorders Aortic aneurysm	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Vascular disorders Aortic dissection	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Vascular disorders Hypertension	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Vascular disorders Iliac artery stenosis	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Vascular disorders Arteriosclerosis obliterans	0.01% 2/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.

Other adverse events

Measure	Candesartan Cilexetil n=13804 participants at risk Candesartan cilexetil 4 mg, tablet, orally, once daily for up to 3 years.
Cardiac disorders Acute myocardial infarction	0.02% 3/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Cardiac disorders Angina pectoris	0.04% 5/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Cardiac disorders Arrhythmia	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Cardiac disorders Atrial fibrillation	0.05% 7/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Cardiac disorders Bradycardia	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Cardiac disorders Cardiac failure	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Cardiac disorders Palpitations	0.03% 4/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Cardiac disorders Sick sinus syndrome	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Cardiac disorders Supraventricular extrasystoles	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Cardiac disorders Ventricular extrasystoles	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Eye disorders Diabetic retinopathy	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Eye disorders Vision blurred	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Abdominal discomfort	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Abdominal distension	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Abdominal pain	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Constipation	0.01% 2/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Diarrhoea	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Nausea	0.02% 3/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Epigastric discomfort	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
General disorders Asthenia	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
General disorders Chest discomfort	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
General disorders Face oedema	0.01% 2/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
General disorders Feeling abnormal	0.01% 2/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
General disorders Feeling hot	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
General disorders Malaise	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
General disorders Oedema	0.01% 2/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
General disorders Oedema peripheral	0.01% 2/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
General disorders Thirst	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Hepatobiliary disorders Jaundice	0.01% 2/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Hepatobiliary disorders Liver disorder	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Cellulitis	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Cholangitis suppurative	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Injury, poisoning and procedural complications Fall	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Injury, poisoning and procedural complications Road traffic accident	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Investigations Alanine aminotransferase increased	0.09% 13/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Investigations Aspartate aminotransferase increased	0.06% 8/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Investigations Blood cholesterol increased	0.04% 5/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Investigations Blood creatine phosphokinase increased	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Investigations Blood creatinine increased	0.12% 17/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Investigations Blood glucose increased	0.01% 2/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Investigations Blood potassium increased	0.07% 9/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Investigations Blood pressure abnormal	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Investigations Blood pressure decreased	0.04% 5/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Investigations Blood triglycerides increased	0.06% 8/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Investigations Blood urea increased	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Investigations Blood uric acid increased	0.12% 16/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Investigations Gamma-glutamyltransferase increased	0.02% 3/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Investigations Glucose urine present	0.01% 2/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Investigations Glycosylated haemoglobin increased	0.02% 3/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Investigations High density lipoprotein decreased	0.01% 2/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Investigations Low density lipoprotein increased	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Investigations Weight decreased	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Investigations Protein urine present	0.01% 2/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Investigations Blood alkaline phosphatase increased	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Metabolism and nutrition disorders Diabetes mellitus	0.05% 7/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Metabolism and nutrition disorders Gout	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Metabolism and nutrition disorders Hyperkalaemia	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Metabolism and nutrition disorders Decreased appetite	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hepatic neoplasm malignant	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders Cerebral haemorrhage	0.04% 5/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders Cerebral infarction	0.04% 5/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders Depressed level of consciousness	0.01% 2/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders Dizziness	0.18% 25/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders Dizziness postural	0.04% 5/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders Headache	0.07% 9/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders Hypoaesthesia	0.01% 2/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders Somnolence	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders Transient ischaemic attack	0.02% 3/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Psychiatric disorders Insomnia	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Renal and urinary disorders Azotaemia	0.01% 2/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Renal and urinary disorders Proteinuria	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Renal and urinary disorders Renal failure	0.02% 3/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Reproductive system and breast disorders Erectile dysfunction	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Respiratory, thoracic and mediastinal disorders Cough	0.05% 7/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Skin and subcutaneous tissue disorders Drug eruption	0.03% 4/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Skin and subcutaneous tissue disorders Eczema	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Skin and subcutaneous tissue disorders Erythema	0.02% 3/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Skin and subcutaneous tissue disorders Henoch-Schonlein purpura	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Skin and subcutaneous tissue disorders Pruritus	0.03% 4/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Skin and subcutaneous tissue disorders Rash	0.03% 4/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Skin and subcutaneous tissue disorders Skin discomfort	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Skin and subcutaneous tissue disorders Urticaria	0.02% 3/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Skin and subcutaneous tissue disorders Photodermatosis	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Skin and subcutaneous tissue disorders Hypoaesthesia facial	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Vascular disorders Flushing	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Vascular disorders Hypertension	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Vascular disorders Hypotension	0.01% 2/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Vascular disorders Orthostatic hypotension	0.01% 2/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Vascular disorders Blood pressure inadequately controlled	0.01% 1/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Vascular disorders Hot flush	0.01% 2/13804 • Baseline up to 3 years At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.

Additional Information

Medical Director

Takeda

Phone: +1-877-825-3327

Email: trialdisclosures@takeda.com

Results disclosure agreements

• Principal investigator is a sponsor employee No publication related to study results will be published prior to publication of a multi-center report submitted for publication within 18 months after conclusion or termination of a study at all study sites. Results publications will be submitted to sponsor for review 60 days in advance of publication. Sponsor can require removal of confidential information unrelated to study results. Sponsor can embargo a proposed publication for another 60 days to preserve intellectual property.
• Publication restrictions are in place

Restriction type: OTHER