Cardiovascular Events
Conditions
Keywords
Aliskiren, Elderly, Major Cardiovascular Events, Effect of aliskiren-based regimen on major CV events (composite of CV death, non-fatal MI, non-fatal stroke and significant heart failure) in the elderly
Brief summary
This study was planned to provide new information regarding the role of aliskiren (with or without additional therapy with a diuretic or a Calcium channel blockers (CCB)) in elderly individuals (≥ 65 years) with systolic blood pressure (SBP) 130 to 159 mmHg, in preventing major cardiovascular (CV) events and on global measures of physical, executive and cognitive function.
Detailed description
This was 2x2 factorial design study with 2 strata. As per protocol, the first co- Primary analysis as well as secondary analysis were aliskiren based regimen vs non-aliskiren based regimen. All aliskiren based arm were combined into the aliskiren based regimen and all non-aliskiren based arms were combined into non-aliskiren based regimen.
Interventions
DRUGAliskiren
Aliskiren 150/300 mg once daily
DRUGAmlodipine
Amlodipine 5 mg
HCTZ 12.5/25 mg
Placebo for Aliskiren 300 mg
DRUGPlacebo for Amlodipine
Placebo for Amlodipine
DRUGPlacebo for Hydrochlorothiazide (HCTZ)
Placebo for HCTZ 12.5/25 mg
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
65 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Systolic blood pressure 130 - 159 mmHg with any one of the following (1, 2 or 3): 1. Men and women aged ≥ 65 years if they have at least one of the following: (secondary prevention) Coronary heart disease * Previous myocardial infarction or * Stable angina or unstable angina with documented multi-vessel coronary artery disease, \> 50% stenosis in at least 2 major coronary arteries on coronary angiography, or positive stress test (ECG or nuclear perfusion scintogram), or * Multi-vessel PCI, or * Multi-vessel CABG surgery \> 4 years prior to informed consent, or with recurrent angina or ischemia following surgery Stroke/TIA Previous documented stroke or documented TIA \< 1 year before informed consent Peripheral artery disease * Previous limb bypass surgery or percutaneous transluminal angioplasty, or * Previous limb or foot amputation, or * History of intermittent claudication, with an ankle:arm BP ratio ≤ 0.80 on at least one side, or significant peripheral artery stenosis (\> 50%) documented by angiography or non-invasive testing * Diabetes mellitus: High-risk diabetics with evidence of end-organ damage 2. Men and women aged ≥ 65 years with no history of CVD, and with at least 1 CV risk factor (primary prevention): * History of dyslipidemia, defined as LDL cholesterol \> 3.5 mmol/L (135 mg/dL) or HDL\< 1.3 mmol/L (50 mg/dL) in women or \< 1.0 mmol/L (39 mg/dL) in men or total cholesterol/HDL ratio \> 5 * History of current or recent smoking (regular tobacco use within 5 years) * Abdominal adiposity defined as waist/hip ratio ≥ 0.90 in women and ≥ 0.95 in men * History of dysglycemia defined as impaired fasting glucose (IFG - fasting plasma glucose 5.6 to 6.9 mmol/L \[101 to 124 mg/dL\]), or impaired glucose tolerance (IGT - fasting plasma glucose \< 7 mmol/L \[126 mg/dL\] but 2 hour glucose 7.8 to 11.0 mmol/L \[140 to 198 mg/dL\]) or type 2 diabetes * Renal dysfunction: eGFR\< 60 ml/min/1.73m2 but \> 30 ml/min/1.73m2 (MDRD formula) and/or microalbuminurea/macroalbuminurea * Clinical evidence of left ventricular hypertrophy 3. Men and women aged ≥ 70 years if they do not have any of the above (primary prevention)
Exclusion criteria
1. Current treatment with aliskiren, an ACE-inhibitor, an ARB or an aldosterone antagonist and unable to discontinue this therapy in those without clinical vascular disease. Individuals with CVD or type 2 diabetes and/or renal dysfunction may receive an ACE-inhibitor or an ARB, but not both, contraindications to Aliskiren, Amlodipine or Hydrochlorothiazide. 2. Use of both thiazide diuretic and amlodipine or another calcium channel blocker. Patients on only one of these two classes of drugs are eligible 3. Uncontrolled hypertension (systolic blood pressure ≥ 160 mmHg and/or diastolic blood pressure ≥ 100 mmHg) 4. Symptomatic heart failure, requiring the use of loop diuretics 5. Hemodynamically significant primary valvular or outflow tract obstruction (e.g. aortic or mitral valve stenosis, asymmetric septal hypertrophy, malfunctioning prosthetic valve). Constrictive pericarditis. Complex congenital heart disease. 6. Acute stroke \< 3 months or TIA ≤ 7 days before informed consent, acute coronary syndrome \< 1 months before informed consent 7. Planned cardiac surgery or angioplasty \< 3 months after informed consent or having had the procedure \< 3 months before informed consent 8. Severe renal impairment eGFR ≤ 30 ml/min/1.73m2 (MDRD formula); known renal artery stenosis ; serum potassium ≥ 5.3 mmol/L 9. Chronic liver disease (i.e. cirrhosis, esophageal varices, portocaval shunt or persistent hepatitis) or abnormal liver function, i.e., alanine transaminase (ALT) or AST \> 3x upper limit of normal (ULN) 10. Concurrent treatment with cyclosporine or quinidine; chronic use of non-steroidal anti-inflammatory drug (NSAIDs) or cyclooxygenase-2 (COX 2) inhibitors in patients with eGFR \< 60 ml/min/1.73m2 (MDRD formula) 11. History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years regardless of whether there is evidence of local recurrence or metastases 12. Other serious condition(s) likely to interfere with study participation or with the ability to complete the study. Significant psychiatric illness, senility, dementia, alcohol or substance abuse, which could impair the ability to provide informed consent and to adhere to the study procedures
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Composite Cardiovascular Endpoints in Aliskiren Based Regimen Versus Non-Aliskiren Based Regimen | End of study (209 days (median)) | The composite CV endpoint is based on the following first adjudicated events: CV death, non-fatal MI,non-fatal stroke, significant heart failure |
| Number of Participants With Composite Cardiovascular Endpoints in Aliskiren+Amlodipine/HCTZ Group Versus All Placebo Group | End of study (209 days (median)) | The composite CV endpoint is based on the following first adjudicated events: CV death, non-fatal MI,non-fatal stroke, significant heart failure |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Standard Assessment of Global Activities in the Elderly (SAGE) Dimensions (Part II) | End of study (209 days [median]) | Decline in ability to perform everyday activities independently was measured primarily by using the Standard Assessment of Global Activities in the Elderly (SAGE) scale. The SAGE was comprised of 15 questions, each describing an activity. Patient had to indicate how much difficulty he/she had encountered in performing the activity in the last month. Each question's score ranges from 0 (No difficulty) to 3 (difficulty levels were mild (score = 1), moderate (score =2) and severe (score=3)). Part II of SAGE included 2 dimensions: * Normal if the scores of all SAGE questions is 0 (i.e., No difficulty) * Mobility Only if scores of both SAGE questions 11 and 12 are 0 |
| Number of Participants With Total Mortality in Aliskiren Based Regimen Versus Non-aliskiren Based Regimen | End of study (209 days (median)) | The total mortality endpoint was defined as time to death from any cause. Total mortality analysis used the date of last follow-up including the washout period as the censoring date. |
| Number of Participants With Renal Dysfunction in Aliskiren Based Regimen Versus Non-Aliskiren Based Regimen | End of study (209 days (median)) | The renal dysfunction (composite endpoint) was defined as the first occurrence of either of the following: * End-stage renal disease \[ESRD\] requiring dialysis or transplantation * Doubling of serum creatinine and reaching an eGFR \< 45 ml/min/1.73 m\^2. |
| Change From Baseline to End of Study in Standard Assessment of Global Activities in the Elderly (SAGE) Dimensions (Part I) | Baseline, End of study (209 days [median]) | Decline in ability to perform everyday activities independently was measured primarily by using the Standard Assessment of Global Activities in the Elderly (SAGE) scale. The SAGE comprised of 15 questions, each describing an activity. Patient had to indicate how much difficulty he/she had encountered in performing the activity in last month. Each question's score ranges from 0 (No difficulty) to 3 (difficulty levels were mild (score = 1), moderate (score =2) and severe (score=3)). Part I of SAGE included 4 dimensions: * Community Cognition (maximum of scores of questions 1 to 6); * Instrumental Activities of daily Living (IADL) (maximum of scores of questions 7 to 10); * Mobility (maximum of scores of questions 11 and 12);. * Basic Activities of daily Living (ADL) (maximum of scores of questions 13 to 15) Each dimension's total score ranged from 0 to 3. 0=best, 3=worst A negative change in value from baseline means improvement in the ability to perform everyday activities. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) | Baseline (BL), 6 week, 6 month and 12 month | Mean sitting systolic blood pressure (msSBP) is the average of 2 sitting SBP measurements (2 minutes apart). Since each patient had their final follow-up visit at a different time in the trial, these measurements were classified as falling into the 6 week, 6 month, or 12 month measurement period. All available blood pressures were sorted within these periods and the last value within each time range used for analysis. At each timepoint, a patient must have both baseline and postbaseline values to be included in the analysis. |
| Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP) | Baseline (BL), 6 week, 6 month and 12 month | Mean sitting diastolic blood pressure (msDBP) is the average of 2 sitting DBP measurements (2 minutes apart). Since each patient had their final follow-up visit at a different time in the trial, these measurements were classified as falling into the 6 week, 6 month, or 12 month measurement period. All available blood pressures were sorted within these periods and the last value within each time range used for analysis. At each timepoint, a patient must have both baseline and postbaseline values to be included in the analysis. |
Countries
Argentina, Brazil, Canada, Chile, Colombia, Czechia, Germany, Hungary, India, Ireland, Israel, Malaysia, Netherlands, Philippines, South Africa, Spain, Sweden, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Aliskiren + Hydrochlorothiazide (HCTZ) In double blind period, all patients who successfully completed run-in with HCTZ plus Aliskiren were randomized equally to the 4 arms of the HCTZ add-on stratum.
Patients randomized to this arm received Aliskiren 300 mg + HCTZ 25 mg once daily. | 244 |
| Aliskiren + Placebo for HCTZ In double blind period, all patients who successfully completed run-in with HCTZ plus Aliskiren were randomized equally to the 4 arms of the HCTZ add-on stratum.
In double blind period, randomized patients to this arm received Aliskiren 300 mg + placebo for HCTZ 25 mg once daily | 232 |
| Aliskiren + Amlodipine In double blind period, all patients who successfully completed run-in with Amlodipine plus Aliskiren were randomized equally to the 4 arms of the Amlodipine add-on stratum.
Patients randomized to this arm received Aliskiren 300 mg + Amlodipine 5 mg once daily during the double blind period. | 189 |
| Aliskiren + Placebo for Amlodipine In double blind period, all patients who successfully completed run-in with Amlodipine plus Aliskiren were randomized equally to the 4 arms of the Amlodipine add-on stratum.
In double blind period, randomized patients to this arm received Aliskiren 300 mg + placebo for Amlodipine 5 mg | 195 |
| HCTZ + Placebo for Aliskiren In double blind period, all patients who successfully completed run-in with HCTZ plus Aliskiren were randomized equally to the 4 arms of the HCTZ add-on stratum.
In double blind period, randomized patients to this arm received HCTZ 25 mg + placebo for Aliskiren 300 mg once daily | 251 |
| Placebo for Aliskiren + Placebo for HCTZ In double blind period, all patients who successfully completed run-in with HCTZ plus Aliskiren were randomized equally to the 4 arms of the HCTZ add-on stratum.
In double blind period, randomized patients to this arm received placebo for Aliskiren 300 mg + placebo for HCTZ 25 mg once daily | 253 |
| Amlodipine + Placebo for Aliskiren In double blind period, all patients who successfully completed run-in with Amlodipine plus Aliskiren were run-in stratum randomized equally to the 4 arms of the Amlodipine add-on stratum.
In double blind period, randomized patients to this arm received Amlodipine 5 mg + placebo for Aliskiren 300 mg once daily | 196 |
| Placebo for Aliskiren + Placebo for Amlodipine In double blind period, all patients who successfully completed run-in with Amlodipine plus Aliskiren were randomized equally to the 4 arms of the Amlodipine add-on stratum.
In double blind period, randomized patients to this arm received placebo for Aliskiren 300 mg + placebo for Amlodipine 5 mg once daily | 199 |
| Total | 1,759 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Double Blind Randomized Period | Death | 1 | 1 | 1 | 2 | 1 | 5 | 2 | 1 |
| Double Blind Randomized Period | Other reasons | 0 | 1 | 0 | 0 | 1 | 2 | 3 | 1 |
| Double Blind Randomized Period | Withdrew informed consent/ refused visit | 1 | 1 | 0 | 2 | 2 | 1 | 1 | 1 |
Baseline characteristics
| Characteristic | Aliskiren + Hydrochlorothiazide (HCTZ) | Aliskiren + Placebo for HCTZ | Aliskiren + Amlodipine | Aliskiren + Placebo for Amlodipine | HCTZ + Placebo for Aliskiren | Placebo for Aliskiren + Placebo for HCTZ | Amlodipine + Placebo for Aliskiren | Placebo for Aliskiren + Placebo for Amlodipine | Total |
|---|---|---|---|---|---|---|---|---|---|
| Age, Customized >=65 to <75 years | 165 participants | 174 participants | 127 participants | 125 participants | 180 participants | 189 participants | 135 participants | 134 participants | 1229 participants |
| Age, Customized >=75 years | 79 participants | 58 participants | 62 participants | 70 participants | 71 participants | 64 participants | 61 participants | 65 participants | 530 participants |
| Sex: Female, Male Female | 119 Participants | 109 Participants | 91 Participants | 89 Participants | 122 Participants | 108 Participants | 87 Participants | 88 Participants | 813 Participants |
| Sex: Female, Male Male | 125 Participants | 123 Participants | 98 Participants | 106 Participants | 129 Participants | 145 Participants | 109 Participants | 111 Participants | 946 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 7 / 1,335 | 19 / 1,001 | 6 / 244 | 5 / 232 | 9 / 189 | 8 / 195 | 6 / 251 | 5 / 253 | 14 / 196 | 3 / 199 |
| serious Total, serious adverse events | 10 / 1,335 | 10 / 1,001 | 8 / 244 | 5 / 232 | 7 / 189 | 8 / 195 | 4 / 251 | 6 / 253 | 3 / 196 | 7 / 199 |
Outcome results
Primary
Number of Participants With Composite Cardiovascular Endpoints in Aliskiren+Amlodipine/HCTZ Group Versus All Placebo Group
The composite CV endpoint is based on the following first adjudicated events: CV death, non-fatal MI,non-fatal stroke, significant heart failure
Time frame: End of study (209 days (median))
Population: Full Analysis set. 1759 patients were randomized as against the originally planned 11,000. A total of 25 primary CV composite endpoints had accrued during median follow-up of 209 days versus planned 2000 primary endpoints during planned follow-up of average 5 years. These low numbers significantly limit interpretation of the results.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aliskiren Based Regimen | Number of Participants With Composite Cardiovascular Endpoints in Aliskiren+Amlodipine/HCTZ Group Versus All Placebo Group | 2 participants |
| Non-Aliskiren Based Regimen | Number of Participants With Composite Cardiovascular Endpoints in Aliskiren+Amlodipine/HCTZ Group Versus All Placebo Group | 8 participants |
Primary
Number of Participants With Composite Cardiovascular Endpoints in Aliskiren Based Regimen Versus Non-Aliskiren Based Regimen
The composite CV endpoint is based on the following first adjudicated events: CV death, non-fatal MI,non-fatal stroke, significant heart failure
Time frame: End of study (209 days (median))
Population: Full Analysis set. 1759 patients were randomized as against the originally planned 11,000. A total of 25 primary CV composite endpoints had accrued during median follow-up of 209 days versus planned 2000 primary endpoints during planned follow-up of average 5 years. These low numbers significantly limit interpretation of the results.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aliskiren Based Regimen | Number of Participants With Composite Cardiovascular Endpoints in Aliskiren Based Regimen Versus Non-Aliskiren Based Regimen | 11 participants |
| Non-Aliskiren Based Regimen | Number of Participants With Composite Cardiovascular Endpoints in Aliskiren Based Regimen Versus Non-Aliskiren Based Regimen | 14 participants |
Secondary
Change From Baseline to End of Study in Standard Assessment of Global Activities in the Elderly (SAGE) Dimensions (Part I)
Decline in ability to perform everyday activities independently was measured primarily by using the Standard Assessment of Global Activities in the Elderly (SAGE) scale. The SAGE comprised of 15 questions, each describing an activity. Patient had to indicate how much difficulty he/she had encountered in performing the activity in last month. Each question's score ranges from 0 (No difficulty) to 3 (difficulty levels were mild (score = 1), moderate (score =2) and severe (score=3)). Part I of SAGE included 4 dimensions: * Community Cognition (maximum of scores of questions 1 to 6); * Instrumental Activities of daily Living (IADL) (maximum of scores of questions 7 to 10); * Mobility (maximum of scores of questions 11 and 12);. * Basic Activities of daily Living (ADL) (maximum of scores of questions 13 to 15) Each dimension's total score ranged from 0 to 3. 0=best, 3=worst A negative change in value from baseline means improvement in the ability to perform everyday activities.
Time frame: Baseline, End of study (209 days [median])
Population: Full Analysis Set: Due to the sparse post-baseline data following early termination of the study, this analysis was not performed as planned in protocol.Hence, no meaningful conclusion could be drawn. Patients who completed both baseline and post-baseline SAGE questionnaires (Part II) were included in this analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Aliskiren Based Regimen | Change From Baseline to End of Study in Standard Assessment of Global Activities in the Elderly (SAGE) Dimensions (Part I) | Instrumental Activities of daily Living (IADL) | -0.06 units on a scale | Standard Deviation 0.562 |
| Aliskiren Based Regimen | Change From Baseline to End of Study in Standard Assessment of Global Activities in the Elderly (SAGE) Dimensions (Part I) | ADL | -0.09 units on a scale | Standard Deviation 0.525 |
| Aliskiren Based Regimen | Change From Baseline to End of Study in Standard Assessment of Global Activities in the Elderly (SAGE) Dimensions (Part I) | Mobility | 0.01 units on a scale | Standard Deviation 0.791 |
| Aliskiren Based Regimen | Change From Baseline to End of Study in Standard Assessment of Global Activities in the Elderly (SAGE) Dimensions (Part I) | Community Cognition | -0.04 units on a scale | Standard Deviation 0.768 |
| Non-Aliskiren Based Regimen | Change From Baseline to End of Study in Standard Assessment of Global Activities in the Elderly (SAGE) Dimensions (Part I) | Mobility | 0.00 units on a scale | Standard Deviation 0.779 |
| Non-Aliskiren Based Regimen | Change From Baseline to End of Study in Standard Assessment of Global Activities in the Elderly (SAGE) Dimensions (Part I) | Instrumental Activities of daily Living (IADL) | -0.04 units on a scale | Standard Deviation 0.505 |
| Non-Aliskiren Based Regimen | Change From Baseline to End of Study in Standard Assessment of Global Activities in the Elderly (SAGE) Dimensions (Part I) | Community Cognition | -0.05 units on a scale | Standard Deviation 0.741 |
| Non-Aliskiren Based Regimen | Change From Baseline to End of Study in Standard Assessment of Global Activities in the Elderly (SAGE) Dimensions (Part I) | ADL | -0.08 units on a scale | Standard Deviation 0.52 |
Secondary
Number of Participants With Renal Dysfunction in Aliskiren Based Regimen Versus Non-Aliskiren Based Regimen
The renal dysfunction (composite endpoint) was defined as the first occurrence of either of the following: * End-stage renal disease \[ESRD\] requiring dialysis or transplantation * Doubling of serum creatinine and reaching an eGFR \< 45 ml/min/1.73 m\^2.
Time frame: End of study (209 days (median))
Population: Full Analysis set. 1759 patients were randomized as against the originally planned 11,000. The duration of study follow-up was 209 days (median) as against the planned follow-up of average 5 years. These low numbers significantly limit interpretation of the results.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Aliskiren Based Regimen | Number of Participants With Renal Dysfunction in Aliskiren Based Regimen Versus Non-Aliskiren Based Regimen | ESRD requiring dialysis or transplantation | 0 participants |
| Aliskiren Based Regimen | Number of Participants With Renal Dysfunction in Aliskiren Based Regimen Versus Non-Aliskiren Based Regimen | Doubling of creatinine & eGFR<45 ml/min/1.73 m^2 | 7 participants |
| Non-Aliskiren Based Regimen | Number of Participants With Renal Dysfunction in Aliskiren Based Regimen Versus Non-Aliskiren Based Regimen | ESRD requiring dialysis or transplantation | 0 participants |
| Non-Aliskiren Based Regimen | Number of Participants With Renal Dysfunction in Aliskiren Based Regimen Versus Non-Aliskiren Based Regimen | Doubling of creatinine & eGFR<45 ml/min/1.73 m^2 | 1 participants |
Secondary
Number of Participants With Total Mortality in Aliskiren Based Regimen Versus Non-aliskiren Based Regimen
The total mortality endpoint was defined as time to death from any cause. Total mortality analysis used the date of last follow-up including the washout period as the censoring date.
Time frame: End of study (209 days (median))
Population: Full Analysis set. 1759 patients were randomized as against the originally planned 11,000. The duration of study follow-up was 209 days (median) as against the planned follow-up of average 5 years. These low numbers significantly limit interpretation of the results.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aliskiren Based Regimen | Number of Participants With Total Mortality in Aliskiren Based Regimen Versus Non-aliskiren Based Regimen | 5 Participants |
| Non-Aliskiren Based Regimen | Number of Participants With Total Mortality in Aliskiren Based Regimen Versus Non-aliskiren Based Regimen | 9 Participants |
Secondary
Percentage of Participants With Standard Assessment of Global Activities in the Elderly (SAGE) Dimensions (Part II)
Decline in ability to perform everyday activities independently was measured primarily by using the Standard Assessment of Global Activities in the Elderly (SAGE) scale. The SAGE was comprised of 15 questions, each describing an activity. Patient had to indicate how much difficulty he/she had encountered in performing the activity in the last month. Each question's score ranges from 0 (No difficulty) to 3 (difficulty levels were mild (score = 1), moderate (score =2) and severe (score=3)). Part II of SAGE included 2 dimensions: * Normal if the scores of all SAGE questions is 0 (i.e., No difficulty) * Mobility Only if scores of both SAGE questions 11 and 12 are 0
Time frame: End of study (209 days [median])
Population: Full Analysis Set. Number of patients with all SAGE questions non-missing for the specific visit are included in this population. Due to the sparse post-baseline data following early termination of the study, this analysis was not performed as planned in protocol.Hence, no meaningful conclusion could be drawn.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Aliskiren Based Regimen | Percentage of Participants With Standard Assessment of Global Activities in the Elderly (SAGE) Dimensions (Part II) | Normal | 44.2 percentage of participants |
| Aliskiren Based Regimen | Percentage of Participants With Standard Assessment of Global Activities in the Elderly (SAGE) Dimensions (Part II) | Mobility Only | 66.8 percentage of participants |
| Non-Aliskiren Based Regimen | Percentage of Participants With Standard Assessment of Global Activities in the Elderly (SAGE) Dimensions (Part II) | Normal | 46.5 percentage of participants |
| Non-Aliskiren Based Regimen | Percentage of Participants With Standard Assessment of Global Activities in the Elderly (SAGE) Dimensions (Part II) | Mobility Only | 68.6 percentage of participants |
Other Pre-specified
Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP)
Mean sitting diastolic blood pressure (msDBP) is the average of 2 sitting DBP measurements (2 minutes apart). Since each patient had their final follow-up visit at a different time in the trial, these measurements were classified as falling into the 6 week, 6 month, or 12 month measurement period. All available blood pressures were sorted within these periods and the last value within each time range used for analysis. At each timepoint, a patient must have both baseline and postbaseline values to be included in the analysis.
Time frame: Baseline (BL), 6 week, 6 month and 12 month
Population: Full analysis Set : All randomized patients, regardless of receiving study medication. n=number of patients with non-missing assessments at baseline and each post-baseline visit.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Aliskiren Based Regimen | Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP) | change from Baseline to 6 week (n=821,867) | -5.6 mmHg | Standard Error 0.31 |
| Aliskiren Based Regimen | Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP) | change from baseline to 6 month (n=730,775) | -4.9 mmHg | Standard Error 0.33 |
| Aliskiren Based Regimen | Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP) | change from baseline to 12 month (n=397,399) | -4.3 mmHg | Standard Error 0.43 |
| Non-Aliskiren Based Regimen | Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP) | change from Baseline to 6 week (n=821,867) | -3.6 mmHg | Standard Error 0.3 |
| Non-Aliskiren Based Regimen | Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP) | change from baseline to 6 month (n=730,775) | -3.5 mmHg | Standard Error 0.32 |
| Non-Aliskiren Based Regimen | Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP) | change from baseline to 12 month (n=397,399) | -3.9 mmHg | Standard Error 0.43 |
Other Pre-specified
Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP)
Mean sitting systolic blood pressure (msSBP) is the average of 2 sitting SBP measurements (2 minutes apart). Since each patient had their final follow-up visit at a different time in the trial, these measurements were classified as falling into the 6 week, 6 month, or 12 month measurement period. All available blood pressures were sorted within these periods and the last value within each time range used for analysis. At each timepoint, a patient must have both baseline and postbaseline values to be included in the analysis.
Time frame: Baseline (BL), 6 week, 6 month and 12 month
Population: Full analysis Set : All randomized patients, regardless of receiving study medication. n=number of patients with non-missing assessments at baseline and each post-baseline visit.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Aliskiren Based Regimen | Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) | change from Baseline to 6 week (n=821,867) | -11.9 mmHg | Standard Error 0.5 |
| Aliskiren Based Regimen | Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) | change from baseline to 6 month (n=730,775) | -10.1 mmHg | Standard Error 0.52 |
| Aliskiren Based Regimen | Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) | change from baseline to 12 month (n=397,399) | -7.7 mmHg | Standard Error 0.68 |
| Non-Aliskiren Based Regimen | Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) | change from Baseline to 6 week (n=821,867) | -8.02 mmHg | Standard Error 0.48 |
| Non-Aliskiren Based Regimen | Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) | change from baseline to 12 month (n=397,399) | -5.8 mmHg | Standard Error 0.68 |
| Non-Aliskiren Based Regimen | Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) | change from baseline to 6 month (n=730,775) | -6.8 mmHg | Standard Error 0.5 |