Heart Failure
Conditions
Keywords
Open-label, single arm mortality/morbidity trial eplerenone chronic systolic heart failure
Brief summary
In an earlier study, eplerenone was shown to improve survival in patients who had heart failure immediately following a heart attack. However, it is not known how patients with established mild-to-moderate heart failure (NYHA Class II), who have the additional risk of sudden death, will respond if treated with eplerenone. In this trial, eplerenone plus standard heart failure medicines is being compared to placebo plus standard heart failure medicines in terms of an additional ability to prolong life and prevent re-hospitalizations for worsening heart failure in these patients. The Data Safety Monitoring Committee (DSMC) observed during its conduct of the protocol-specified second interim analysis on the 6th of May, 2010 that the efficacy of eplerenone had met the pre-specified stopping rules in the protocol. As a result of the discussion between the DSMC and the Executive Steering Committee (ESC), the ESC recommended that EMPHASIS-HF should be terminated, Based on the convincing efficacy and the consideration that it would be unethical not to offer this treatment to patients, the ESC recommended that all the patients in the trial should be transferred to open-label eplerenone. The Open Label Extension eplerenone arm will last for 12 months. Eplerenone is not currently approved for the indication studied in this patient population. On May 26, 2010, further enrollment into EMPHASIS-HF was stopped. The amendment is considered to be the most appropriate way to ensure that all the subjects who participated in the double-blind phase of the EMPHASIS-HF trial can be offered treatment with eplerenone
Interventions
DRUGEplerenone
Eplerenone administered on top of background standard heart failure therapy
Sponsors
Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
55 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* History (Hx) of chronic systolic heart failure of ischemic or non-ischemic etiology of at least 4 weeks duration; Currently, New York Heart Association (NYHA) functional Class II and on optimal dose, or maximally tolerated dose of standard heart failure medicines (advisable to include ACE-I/ARBs; beta-blockers) and diuretics if indicated for fluid overload. Should have participated in the double-blind phase of the EMPHASIS-HF trial
Exclusion criteria
* Severe chronic systolic heart failure symptomatic at rest despite optimal medical therapy; estimated glomerular filtration rate (eGFR) \<30 ml/min/1.73m2.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With First Occurrence of Cardiovascular (CV) Mortality or Hospitalization Due to Heart Failure (HF) (Adjudicated): Up to Cut-off Date | Baseline (30 March 2006) up to 50 months (cut-off date: 25 May 2010) | CV mortality is defined as death due to heart failure, myocardial infarction, cardiac arrhythmia, stroke or cerebral vascular accident (CVA), other CV cause (such as aneurysm or pulmonary embolism). Hospitalization due to HF is defined as an overnight stay, or longer, in a hospital environment (emergency room, observation unit or in-patient care, or similar facility including admission to a day care facility) due to HF as the primary reason for hospitalization as determined by the endpoint committee adjudicator. |
| Number of Participants With First Occurrence of Cardiovascular (CV) Mortality or Hospitalization Due to Heart Failure (HF) (Adjudicated) | Baseline (30 March 2006) up to 59.5 months (complete DB phase: 18 March 2011) | CV mortality is defined as death due to heart failure, myocardial infarction, cardiac arrhythmia, stroke or cerebral vascular accident (CVA), other CV cause (such as aneurysm or pulmonary embolism). Hospitalization due to HF is defined as an overnight stay, or longer, in a hospital environment (emergency room, observation unit or in-patient care, or similar facility including admission to a day care facility) due to HF as the primary reason for hospitalization as determined by the endpoint committee adjudicator. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With First Occurrence of All-Cause Mortality (Adjudicated) | Baseline (30 March 2006) up to 50 months (cut-off date: 25 May 2010), 59.5 months (complete DB phase: 18 March 2011) | Death due to any cause. |
| Number of Participants With First Occurrence of Cardiovascular (CV) Mortality (Adjudicated) | Baseline (30 March 2006) up to 50 months (cut-off date: 25 May 2010), 59.5 months (complete DB phase: 18 March 2011) | CV mortality is defined as death due to heart failure, myocardial infarction, cardiac arrhythmia, stroke or cerebral vascular accident (CVA), other CV cause (such as aneurysm or pulmonary embolism). |
| Number of Participants With First Occurrence of Heart Failure (HF) Hospitalization (Adjudicated) | Baseline (30 March 2006) up to 50 months (cut-off date: 25 May 2010), 59.5 months (complete DB phase: 18 March 2011) | First occurrence of HF hospitalization. Hospitalization due to HF is defined as an overnight stay, or longer, in a hospital environment (emergency room, observation unit or in-patient care, or similar facility including admission to a day care facility) due to HF as the primary reason for hospitalization as determined by the endpoint committee adjudicator. |
| Number of Participants With First Occurrence of All-Cause Mortality or All-Cause Hospitalization (Adjudicated) | Baseline (30 March 2006) up to 50 months (cut-off date: 25 May 2010), 59.5 months (complete DB phase: 18 March 2011) | Death due to any cause or hospitalization due to any cause. Hospitalization due to any cause is defined as an overnight stay, or longer, in a hospital environment (emergency room, observation unit or in-patient care, or similar facility including admission to a day care facility). |
| Number of Participants With First Occurrence Of Heart Failure (HF) Mortality or Heart Failure (HF) Hospitalization (Adjudicated) | Baseline (30 March 2006) up to 50 months (cut-off date: 25 May 2010), 59.5 months (complete DB phase: 18 March 2011) | Death due to HF or first occurrence of HF hospitalization. Hospitalization due to HF is defined as an overnight stay, or longer, in a hospital environment (emergency room, observation unit or in-patient care, or similar facility including admission to a day care facility) due to HF as the primary reason for hospitalization as determined by the endpoint committee adjudicator. |
| Number of Participants With First Occurrence of Cardiovascular (CV) Hospitalization (Adjudicated) | Baseline (30 March 2006) up to 50 months (cut-off date: 25 May 2010), 59.5 months (complete DB phase: 18 March 2011) | First occurrence of CV hospitalization. CV hospitalization is defined as hospitalization due to HF (first or subsequent), acute myocardial infarction, angina pectoris (unstable), cardiac arrhythmia (atrial fibrillation \[AF\], atrial flutter, supraventricular arrhythmias, or ventricular arrhythmias), stroke/CVA, other CV reasons (such as hypotension or peripheral vascular disease), implantation of a cardioverter defibrillator (ICD), or cardiac resynchronization therapy (CRT) with CV event as the primary reason for hospitalization as determined by endpoint committee adjudicator. |
| Number of Participants With First Occurrence of Fatal or Non-fatal Myocardial Infarction (Adjudicated) | Baseline (30 March 2006) up to 50 months (cut-off date: 25 May 2010), 59.5 months (complete DB phase: 18 March 2011) | — |
| Number of Participants With First Occurrence of All-Cause Hospitalization (Adjudicated) | Baseline (30 March 2006) up to 50 months (cut-off date: 25 May 2010), 59.5 months (complete DB phase: 18 March 2011) | Hospitalization due to any cause is defined as an overnight stay, or longer, in a hospital environment (emergency room, observation unit or in-patient care, or similar facility including admission to a day care facility). |
| Number of Participants With First Occurrence of Implantation of Cardiac Defibrillator (ICD) (Adjudicated) | Baseline (30 March 2006) up to 50 months (cut-off date: 25 May 2010), 59.5 months (complete DB phase: 18 March 2011) | First occurrence of implantation of cardiac defibrillator (ICD). ICD is an electronic device capable of monitoring the heart rhythm. When the heart is beating normally, the device remains inactive. If the heart develops a life-threatening tachycardia, the ICD delivers electrical shocks to the heart to terminate the abnormal rhythm and return the heart rhythm to normal. |
| Number of Participants With First Occurrence of Implantation of Resynchronization Device (Cardiac Resynchronization Therapy [CRT]) (Adjudicated) | Baseline (30 March 2006) up to 50 months (cut-off date: 25 May 2010), 59.5 months (complete DB phase: 18 March 2011) | First occurrence of implantation of resynchronization device. CRT is use of a specialized pacemaker to re-coordinate the action of the right and left ventricles in heart failure. |
| Number of Participants With First Occurrence of Hospitalization Due to Worsening Renal Function (Adjudicated) | Baseline (30 March 2006) up to 50 months (cut-off date: 25 May 2010), 59.5 months (complete DB phase: 18 March 2011) | First occurrence of hospitalization due to worsening renal function. Hospitalization due to worsening renal function is defined as an overnight stay, or longer, in a hospital environment (emergency room, observation unit or in-patient care, or similar facility including admission to a day care facility) due to worsening renal function as the primary reason for hospitalization as determined by endpoint committee adjudicator. Worsening renal function is defined as doubling of serum creatinine level from baseline level. |
| Number of Participants With First Occurrence of Hospitalization Due to Hyperkalemia (Adjudicated) | Baseline (30 March 2006) up to 50 months (cut-off date: 25 May 2010), 59.5 months (complete DB phase: 18 March 2011) | First occurrence of hospitalization due to hyperkalemia. Hospitalization due to hyperkalemia is defined as an overnight stay, or longer, in a hospital environment (emergency room, observation unit or in-patient care, or similar facility including admission to a day care facility) due to hyperkalemia as the primary reason for hospitalization as determined by endpoint committee adjudicator. Hyperkalemia is defined as serum potassium level greater than (\>) 5.5 milliequivalents per liter (mEq/L). |
| Number of Participants With New Onset Atrial Fibrillation or Flutter | Baseline (30 March 2006) up to 50 months (cut-off date: 25 May 2010), 59.5 months (complete DB phase: 18 March 2011) | New onset of atrial fibrillation or flutter is defined as the diagnosis of atrial fibrillation or flutter in a participant after randomization, where atrial fibrillation was not present before randomization. |
| Number of Participants With New Onset Diabetes Mellitus (DM) | Baseline (30 March 2006) up to 50 months (cut-off date: 25 May 2010), 59.5 months (complete DB phase: 18 March 2011) | The definition of new onset diabetes mellitus is the diagnosis of diabetes mellitus in a participant after randomization, when DM was not present before randomization. |
| Number of Participants With First Occurrence of Fatal or Non-fatal Stroke (Adjudicated) | Baseline (30 March 2006) up to 50 months (cut-off date: 25 May 2010), 59.5 months (complete DB phase: 18 March 2011) | — |
| Number of Participants With First Occurrence of All-Cause Mortality or Heart Failure (HF) Hospitalization (Adjudicated) | Baseline (30 March 2006) up to 50 months (cut-off date: 25 May 2010), 59.5 months (complete DB phase: 18 March 2011) | Death due to any cause or first of occurrence HF hospitalization. HF hospitalization is defined as an overnight stay, or longer, in a hospital environment (emergency room, observation unit or in-patient care, or similar facility including admission to a day care facility) due to HF as the primary reason for hospitalization as determined by the endpoint committee adjudicator. |
Countries
Argentina, Australia, Belgium, Canada, Czechia, France, Germany, Greece, Hong Kong, Hungary, India, Ireland, Italy, Mexico, Netherlands, Poland, Portugal, Russia, Singapore, Slovakia, South Africa, South Korea, Spain, Sweden, Ukraine, United Arab Emirates, United Kingdom, United States, Venezuela
Participant flow
Pre-assignment details
A total of 1597 participants who completed the double-blind phase, 1246 entered into the open-label phase and 351 participants were ineligible to participate the open-label phase.
Participants by arm
| Arm | Count |
|---|---|
| Eplerenone Eplerenone 25 milligram (mg) tablet orally once daily on top of standard heart failure therapy. Dose might have been increased at Week 4 to 50 mg once daily. For participants with an estimated glomerular filtration rate (eGFR) between 30 to 49 milliliter per minute divided by 1.73 squared meter (ml/min/1.73m\^2), initial dose was 25 mg orally once every other day; at Week 4, dose might have been increased to a maximum of 25 mg once daily based on serum potassium level. | 1,367 |
| Placebo Placebo matching to eplerenone 25 mg orally once daily on top of standard heart failure therapy. | 1,376 |
| Total | 2,743 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Double-blind (DB) Phase | Adverse Event | 83 | 100 | 0 |
| Double-blind (DB) Phase | Death | 186 | 222 | 0 |
| Double-blind (DB) Phase | Laboratory abnormality | 6 | 7 | 0 |
| Double-blind (DB) Phase | Lost to Follow-up | 34 | 28 | 0 |
| Double-blind (DB) Phase | Other | 70 | 75 | 0 |
| Double-blind (DB) Phase | Protocol Violation | 28 | 21 | 0 |
| Double-blind (DB) Phase | Randomized but not treated | 3 | 4 | 0 |
| Double-blind (DB) Phase | Withdrawal by Subject | 131 | 148 | 0 |
| Open Label Phase | Adverse Event | 0 | 0 | 25 |
| Open Label Phase | Death | 0 | 0 | 48 |
| Open Label Phase | Laboratory abnormality | 0 | 0 | 10 |
| Open Label Phase | Lost to Follow-up | 0 | 0 | 5 |
| Open Label Phase | Other | 0 | 0 | 16 |
| Open Label Phase | Protocol Violation | 0 | 0 | 3 |
| Open Label Phase | Randomized but not treated | 0 | 0 | 1 |
| Open Label Phase | Study terminated by sponsor | 0 | 0 | 3 |
| Open Label Phase | Withdrawal by Subject | 0 | 0 | 37 |
Baseline characteristics
| Characteristic | Eplerenone | Total | Placebo |
|---|---|---|---|
| Age, Customized 65 to 74 years | 594 participants | 1201 participants | 607 participants |
| Age, Customized 75 to 84 years | 302 participants | 601 participants | 299 participants |
| Age, Customized Greater than or equal to (>=) 85 years | 28 participants | 57 participants | 29 participants |
| Age, Customized Less than (<) 65 years | 443 participants | 884 participants | 441 participants |
| Sex: Female, Male Female | 309 Participants | 611 Participants | 302 Participants |
| Sex: Female, Male Male | 1058 Participants | 2132 Participants | 1074 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 |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 547 / 1,360 | 540 / 1,369 | 640 / 1,364 | 617 / 1,372 | 329 / 1,245 |
| serious Total, serious adverse events | 509 / 1,360 | 614 / 1,369 | 586 / 1,364 | 686 / 1,372 | 251 / 1,245 |
Outcome results
Primary
Number of Participants With First Occurrence of Cardiovascular (CV) Mortality or Hospitalization Due to Heart Failure (HF) (Adjudicated)
CV mortality is defined as death due to heart failure, myocardial infarction, cardiac arrhythmia, stroke or cerebral vascular accident (CVA), other CV cause (such as aneurysm or pulmonary embolism). Hospitalization due to HF is defined as an overnight stay, or longer, in a hospital environment (emergency room, observation unit or in-patient care, or similar facility including admission to a day care facility) due to HF as the primary reason for hospitalization as determined by the endpoint committee adjudicator.
Time frame: Baseline (30 March 2006) up to 59.5 months (complete DB phase: 18 March 2011)
Population: FAS using ITT principle: All randomized participants, followed for mortality and other major endpoints for the duration of the double blind treatment period, regardless of compliance with the study drug and the protocol.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Eplerenone: Double-blind Phase | Number of Participants With First Occurrence of Cardiovascular (CV) Mortality or Hospitalization Due to Heart Failure (HF) (Adjudicated) | 288 participants |
| Placebo: Double-blind Phase | Number of Participants With First Occurrence of Cardiovascular (CV) Mortality or Hospitalization Due to Heart Failure (HF) (Adjudicated) | 392 participants |
Primary
Number of Participants With First Occurrence of Cardiovascular (CV) Mortality or Hospitalization Due to Heart Failure (HF) (Adjudicated): Up to Cut-off Date
CV mortality is defined as death due to heart failure, myocardial infarction, cardiac arrhythmia, stroke or cerebral vascular accident (CVA), other CV cause (such as aneurysm or pulmonary embolism). Hospitalization due to HF is defined as an overnight stay, or longer, in a hospital environment (emergency room, observation unit or in-patient care, or similar facility including admission to a day care facility) due to HF as the primary reason for hospitalization as determined by the endpoint committee adjudicator.
Time frame: Baseline (30 March 2006) up to 50 months (cut-off date: 25 May 2010)
Population: Full analysis set (FAS) using intent-to-treat (ITT) principle: All randomized participants, followed for mortality, other major endpoints for duration of double blind treatment period, regardless of compliance with study drug and protocol. Here 'N' (Number of Participants Analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Eplerenone: Double-blind Phase | Number of Participants With First Occurrence of Cardiovascular (CV) Mortality or Hospitalization Due to Heart Failure (HF) (Adjudicated): Up to Cut-off Date | 249 participants |
| Placebo: Double-blind Phase | Number of Participants With First Occurrence of Cardiovascular (CV) Mortality or Hospitalization Due to Heart Failure (HF) (Adjudicated): Up to Cut-off Date | 356 participants |
Comparison: Cox proportional hazard model includes treatment as the major factor, adjusting for age, estimated glomerular filtration rate, left ventricular ejection fraction, body mass index, hemoglobin, heart rate, systolic blood pressure, diabetes, history of hypertension, prior myocardial infarction, baseline left bundle branch block, time from electrocardiogram Q wave to the end of the S wave corresponding to ventricle depolarization (QRS) and atrial fibrillation as covariates.p-value: <0.000195% CI: [0.535, 0.741]Cox proportional hazard model
Secondary
Number of Participants With First Occurrence of All-Cause Hospitalization (Adjudicated)
Hospitalization due to any cause is defined as an overnight stay, or longer, in a hospital environment (emergency room, observation unit or in-patient care, or similar facility including admission to a day care facility).
Time frame: Baseline (30 March 2006) up to 50 months (cut-off date: 25 May 2010), 59.5 months (complete DB phase: 18 March 2011)
Population: FAS using ITT principle: All randomized participants, followed for mortality and other major endpoints for the duration of the double blind treatment period, regardless of compliance with the study drug and the protocol. Here n signifies participants evaluated at that time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Eplerenone: Double-blind Phase | Number of Participants With First Occurrence of All-Cause Hospitalization (Adjudicated) | Up to 50 months (cut-off) (n= 1364, 1373) | 408 participants |
| Eplerenone: Double-blind Phase | Number of Participants With First Occurrence of All-Cause Hospitalization (Adjudicated) | Up to 59.5 months (complete DB) (n= 1367, 1376) | 463 participants |
| Placebo: Double-blind Phase | Number of Participants With First Occurrence of All-Cause Hospitalization (Adjudicated) | Up to 50 months (cut-off) (n= 1364, 1373) | 491 participants |
| Placebo: Double-blind Phase | Number of Participants With First Occurrence of All-Cause Hospitalization (Adjudicated) | Up to 59.5 months (complete DB) (n= 1367, 1376) | 552 participants |
Comparison: The statistical analysis was only performed on the adjudicated endpoint data up to cut-off. Cox proportional hazard model includes treatment as the major factor, adjusting for age, estimated glomerular filtration rate, left ventricular ejection fraction, body mass index, hemoglobin, heart rate, systolic blood pressure, diabetes, history of hypertension, prior myocardial infarction, baseline left bundle branch block, QRS complex and atrial fibrillation as covariates.p-value: <0.000195% CI: [0.673, 0.876]Cox proportional hazard model
Secondary
Number of Participants With First Occurrence of All-Cause Mortality (Adjudicated)
Death due to any cause.
Time frame: Baseline (30 March 2006) up to 50 months (cut-off date: 25 May 2010), 59.5 months (complete DB phase: 18 March 2011)
Population: FAS using ITT principle: All randomized participants, followed for mortality and other major endpoints for the duration of the double blind treatment period, regardless of compliance with the study drug and the protocol. Here n signifies participants evaluated at that time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Eplerenone: Double-blind Phase | Number of Participants With First Occurrence of All-Cause Mortality (Adjudicated) | Up to 50 months (cut-off) (n= 1364, 1373) | 171 participants |
| Eplerenone: Double-blind Phase | Number of Participants With First Occurrence of All-Cause Mortality (Adjudicated) | Up to 59.5 months (complete DB) (n= 1367, 1376) | 205 participants |
| Placebo: Double-blind Phase | Number of Participants With First Occurrence of All-Cause Mortality (Adjudicated) | Up to 50 months (cut-off) (n= 1364, 1373) | 213 participants |
| Placebo: Double-blind Phase | Number of Participants With First Occurrence of All-Cause Mortality (Adjudicated) | Up to 59.5 months (complete DB) (n= 1367, 1376) | 253 participants |
Comparison: The statistical analysis was only performed on the adjudicated endpoint data up to cut-off. Cox proportional hazard model includes treatment as the major factor, adjusting for age, estimated glomerular filtration rate, left ventricular ejection fraction, body mass index, hemoglobin, heart rate, systolic blood pressure, diabetes, history of hypertension, prior myocardial infarction, baseline left bundle branch block, QRS complex and atrial fibrillation as covariates.p-value: 0.008195% CI: [0.622, 0.932]Cox proportional hazard model
Secondary
Number of Participants With First Occurrence of All-Cause Mortality or All-Cause Hospitalization (Adjudicated)
Death due to any cause or hospitalization due to any cause. Hospitalization due to any cause is defined as an overnight stay, or longer, in a hospital environment (emergency room, observation unit or in-patient care, or similar facility including admission to a day care facility).
Time frame: Baseline (30 March 2006) up to 50 months (cut-off date: 25 May 2010), 59.5 months (complete DB phase: 18 March 2011)
Population: FAS using ITT principle: All randomized participants, followed for mortality and other major endpoints for the duration of the double blind treatment period, regardless of compliance with the study drug and the protocol. Here n signifies participants evaluated at that time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Eplerenone: Double-blind Phase | Number of Participants With First Occurrence of All-Cause Mortality or All-Cause Hospitalization (Adjudicated) | Up to 50 months (cut-off) (n= 1364, 1373) | 462 participants |
| Eplerenone: Double-blind Phase | Number of Participants With First Occurrence of All-Cause Mortality or All-Cause Hospitalization (Adjudicated) | Up to 59.5 months (complete DB) (n= 1367, 1376) | 530 participants |
| Placebo: Double-blind Phase | Number of Participants With First Occurrence of All-Cause Mortality or All-Cause Hospitalization (Adjudicated) | Up to 50 months (cut-off) (n= 1364, 1373) | 569 participants |
| Placebo: Double-blind Phase | Number of Participants With First Occurrence of All-Cause Mortality or All-Cause Hospitalization (Adjudicated) | Up to 59.5 months (complete DB) (n= 1367, 1376) | 636 participants |
Comparison: The statistical analysis was only performed on the adjudicated endpoint data up to cut-off. Cox proportional hazard model includes treatment as the major factor, adjusting for age, estimated glomerular filtration rate, left ventricular ejection fraction, body mass index, hemoglobin, heart rate, systolic blood pressure, diabetes, history of hypertension, prior myocardial infarction, baseline left bundle branch block, QRS complex and atrial fibrillation as covariates.p-value: <0.000195% CI: [0.664, 0.849]Cox proportional hazard model
Secondary
Number of Participants With First Occurrence of All-Cause Mortality or Heart Failure (HF) Hospitalization (Adjudicated)
Death due to any cause or first of occurrence HF hospitalization. HF hospitalization is defined as an overnight stay, or longer, in a hospital environment (emergency room, observation unit or in-patient care, or similar facility including admission to a day care facility) due to HF as the primary reason for hospitalization as determined by the endpoint committee adjudicator.
Time frame: Baseline (30 March 2006) up to 50 months (cut-off date: 25 May 2010), 59.5 months (complete DB phase: 18 March 2011)
Population: FAS using ITT principle: All randomized participants, followed for mortality and other major endpoints for the duration of the double blind treatment period, regardless of compliance with the study drug and the protocol. Here n signifies participants evaluated at that time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Eplerenone: Double-blind Phase | Number of Participants With First Occurrence of All-Cause Mortality or Heart Failure (HF) Hospitalization (Adjudicated) | Up to 50 months (cut-off) (n= 1364, 1373) | 270 participants |
| Eplerenone: Double-blind Phase | Number of Participants With First Occurrence of All-Cause Mortality or Heart Failure (HF) Hospitalization (Adjudicated) | Up to 59.5 months (complete DB) (n= 1367, 1376) | 311 participants |
| Placebo: Double-blind Phase | Number of Participants With First Occurrence of All-Cause Mortality or Heart Failure (HF) Hospitalization (Adjudicated) | Up to 50 months (cut-off) (n= 1364, 1373) | 376 participants |
| Placebo: Double-blind Phase | Number of Participants With First Occurrence of All-Cause Mortality or Heart Failure (HF) Hospitalization (Adjudicated) | Up to 59.5 months (complete DB) (n= 1367, 1376) | 418 participants |
Comparison: The statistical analysis was only performed on the adjudicated endpoint data up to cut-off. Cox proportional hazard model includes treatment as the major factor, adjusting for age, estimated glomerular filtration rate, left ventricular ejection fraction, body mass index, hemoglobin, heart rate, systolic blood pressure, diabetes, history of hypertension, prior myocardial infarction, baseline left bundle branch block, QRS complex and atrial fibrillation as covariates.p-value: <0.000195% CI: [0.552, 0.757]Cox proportional hazard model
Secondary
Number of Participants With First Occurrence of Cardiovascular (CV) Hospitalization (Adjudicated)
First occurrence of CV hospitalization. CV hospitalization is defined as hospitalization due to HF (first or subsequent), acute myocardial infarction, angina pectoris (unstable), cardiac arrhythmia (atrial fibrillation \[AF\], atrial flutter, supraventricular arrhythmias, or ventricular arrhythmias), stroke/CVA, other CV reasons (such as hypotension or peripheral vascular disease), implantation of a cardioverter defibrillator (ICD), or cardiac resynchronization therapy (CRT) with CV event as the primary reason for hospitalization as determined by endpoint committee adjudicator.
Time frame: Baseline (30 March 2006) up to 50 months (cut-off date: 25 May 2010), 59.5 months (complete DB phase: 18 March 2011)
Population: FAS using ITT principle: All randomized participants, followed for mortality and other major endpoints for the duration of the double blind treatment period, regardless of compliance with the study drug and the protocol. Here n signifies participants evaluated at that time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Eplerenone: Double-blind Phase | Number of Participants With First Occurrence of Cardiovascular (CV) Hospitalization (Adjudicated) | Up to 50 months (cut-off) (n= 1364, 1373) | 304 participants |
| Eplerenone: Double-blind Phase | Number of Participants With First Occurrence of Cardiovascular (CV) Hospitalization (Adjudicated) | Up to 59.5 months (complete DB) (n= 1367, 1376) | 346 participants |
| Placebo: Double-blind Phase | Number of Participants With First Occurrence of Cardiovascular (CV) Hospitalization (Adjudicated) | Up to 50 months (cut-off) (n= 1364, 1373) | 399 participants |
| Placebo: Double-blind Phase | Number of Participants With First Occurrence of Cardiovascular (CV) Hospitalization (Adjudicated) | Up to 59.5 months (complete DB) (n= 1367, 1376) | 439 participants |
Comparison: The statistical analysis was only performed on the adjudicated endpoint data up to cut-off. Cox proportional hazard model includes treatment as the major factor, adjusting for age, estimated glomerular filtration rate, left ventricular ejection fraction, body mass index, hemoglobin, heart rate, systolic blood pressure, diabetes, history of hypertension, prior myocardial infarction, baseline left bundle branch block, QRS complex and atrial fibrillation as covariates.p-value: <0.000195% CI: [0.598, 0.806]Cox proportional hazard model
Secondary
Number of Participants With First Occurrence of Cardiovascular (CV) Mortality (Adjudicated)
CV mortality is defined as death due to heart failure, myocardial infarction, cardiac arrhythmia, stroke or cerebral vascular accident (CVA), other CV cause (such as aneurysm or pulmonary embolism).
Time frame: Baseline (30 March 2006) up to 50 months (cut-off date: 25 May 2010), 59.5 months (complete DB phase: 18 March 2011)
Population: FAS using ITT principle: All randomized participants, followed for mortality and other major endpoints for the duration of the double blind treatment period, regardless of compliance with the study drug and the protocol. Here n signifies participants evaluated at that time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Eplerenone: Double-blind Phase | Number of Participants With First Occurrence of Cardiovascular (CV) Mortality (Adjudicated) | Up to 50 months (cut-off) (n= 1364, 1373) | 147 participants |
| Eplerenone: Double-blind Phase | Number of Participants With First Occurrence of Cardiovascular (CV) Mortality (Adjudicated) | Up to 59.5 months (complete DB) (n= 1367, 1376) | 178 participants |
| Placebo: Double-blind Phase | Number of Participants With First Occurrence of Cardiovascular (CV) Mortality (Adjudicated) | Up to 50 months (cut-off) (n= 1364, 1373) | 185 participants |
| Placebo: Double-blind Phase | Number of Participants With First Occurrence of Cardiovascular (CV) Mortality (Adjudicated) | Up to 59.5 months (complete DB) (n= 1367, 1376) | 215 participants |
Comparison: The statistical analysis was only performed on the adjudicated endpoint data up to cut-off. Cox proportional hazard model includes treatment as the major factor, adjusting for age, estimated glomerular filtration rate, left ventricular ejection fraction, body mass index, hemoglobin, heart rate, systolic blood pressure, diabetes, history of hypertension, prior myocardial infarction, baseline left bundle branch block, QRS complex and atrial fibrillation as covariates.p-value: 0.01295% CI: [0.609, 0.941]Cox proportional hazard model
Secondary
Number of Participants With First Occurrence of Fatal or Non-fatal Myocardial Infarction (Adjudicated)
Time frame: Baseline (30 March 2006) up to 50 months (cut-off date: 25 May 2010), 59.5 months (complete DB phase: 18 March 2011)
Population: FAS using ITT principle: All randomized participants, followed for mortality and other major endpoints for the duration of the double blind treatment period, regardless of compliance with the study drug and the protocol. Here n signifies participants evaluated at that time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Eplerenone: Double-blind Phase | Number of Participants With First Occurrence of Fatal or Non-fatal Myocardial Infarction (Adjudicated) | Up to 50 months (cut-off) (n= 1364, 1373) | 45 participants |
| Eplerenone: Double-blind Phase | Number of Participants With First Occurrence of Fatal or Non-fatal Myocardial Infarction (Adjudicated) | Up to 59.5 months (complete DB) (n= 1367, 1376) | 49 participants |
| Placebo: Double-blind Phase | Number of Participants With First Occurrence of Fatal or Non-fatal Myocardial Infarction (Adjudicated) | Up to 50 months (cut-off) (n= 1364, 1373) | 33 participants |
| Placebo: Double-blind Phase | Number of Participants With First Occurrence of Fatal or Non-fatal Myocardial Infarction (Adjudicated) | Up to 59.5 months (complete DB) (n= 1367, 1376) | 40 participants |
Comparison: The statistical analysis was only performed on the adjudicated endpoint data up to cut-off. Cox proportional hazard model includes treatment as the major factor, adjusting for age, estimated glomerular filtration rate, left ventricular ejection fraction, body mass index, hemoglobin, heart rate, systolic blood pressure, diabetes, history of hypertension, prior myocardial infarction, baseline left bundle branch block, QRS complex and atrial fibrillation as covariates.p-value: 0.232195% CI: [0.839, 2.064]Cox proportional hazard model
Secondary
Number of Participants With First Occurrence of Fatal or Non-fatal Stroke (Adjudicated)
Time frame: Baseline (30 March 2006) up to 50 months (cut-off date: 25 May 2010), 59.5 months (complete DB phase: 18 March 2011)
Population: FAS using ITT principle: All randomized participants, followed for mortality and other major endpoints for the duration of the double blind treatment period, regardless of compliance with the study drug and the protocol. Here n signifies participants evaluated at that time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Eplerenone: Double-blind Phase | Number of Participants With First Occurrence of Fatal or Non-fatal Stroke (Adjudicated) | Up to 50 months (cut-off) (n= 1364, 1373) | 21 participants |
| Eplerenone: Double-blind Phase | Number of Participants With First Occurrence of Fatal or Non-fatal Stroke (Adjudicated) | Up to 59.5 months (complete DB) (n= 1367, 1376) | 24 participants |
| Placebo: Double-blind Phase | Number of Participants With First Occurrence of Fatal or Non-fatal Stroke (Adjudicated) | Up to 50 months (cut-off) (n= 1364, 1373) | 26 participants |
| Placebo: Double-blind Phase | Number of Participants With First Occurrence of Fatal or Non-fatal Stroke (Adjudicated) | Up to 59.5 months (complete DB) (n= 1367, 1376) | 31 participants |
Comparison: The statistical analysis was only performed on the adjudicated endpoint data up to cut-off. Cox proportional hazard model includes treatment as the major factor, adjusting for age, estimated glomerular filtration rate, left ventricular ejection fraction, body mass index, hemoglobin, heart rate, systolic blood pressure, diabetes, history of hypertension, prior myocardial infarction, baseline left bundle branch block, QRS complex and atrial fibrillation as covariates.p-value: 0.421395% CI: [0.443, 1.406]Cox proportional hazard model
Secondary
Number of Participants With First Occurrence of Heart Failure (HF) Hospitalization (Adjudicated)
First occurrence of HF hospitalization. Hospitalization due to HF is defined as an overnight stay, or longer, in a hospital environment (emergency room, observation unit or in-patient care, or similar facility including admission to a day care facility) due to HF as the primary reason for hospitalization as determined by the endpoint committee adjudicator.
Time frame: Baseline (30 March 2006) up to 50 months (cut-off date: 25 May 2010), 59.5 months (complete DB phase: 18 March 2011)
Population: FAS using ITT principle: All randomized participants, followed for mortality and other major endpoints for the duration of the double blind treatment period, regardless of compliance with the study drug and the protocol. Here n signifies participants evaluated at that time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Eplerenone: Double-blind Phase | Number of Participants With First Occurrence of Heart Failure (HF) Hospitalization (Adjudicated) | Up to 50 months (cut-off) (n= 1364, 1373) | 164 participants |
| Eplerenone: Double-blind Phase | Number of Participants With First Occurrence of Heart Failure (HF) Hospitalization (Adjudicated) | Up to 59.5 months (complete DB) (n= 1367, 1376) | 186 participants |
| Placebo: Double-blind Phase | Number of Participants With First Occurrence of Heart Failure (HF) Hospitalization (Adjudicated) | Up to 50 months (cut-off) (n= 1364, 1373) | 253 participants |
| Placebo: Double-blind Phase | Number of Participants With First Occurrence of Heart Failure (HF) Hospitalization (Adjudicated) | Up to 59.5 months (complete DB) (n= 1367, 1376) | 277 participants |
Comparison: The statistical analysis was only performed on the adjudicated endpoint data up to cut-off. Cox proportional hazard model includes treatment as the major factor, adjusting for age, estimated glomerular filtration rate, left ventricular ejection fraction, body mass index, hemoglobin, heart rate, systolic blood pressure, diabetes, history of hypertension, prior myocardial infarction, baseline left bundle branch block, QRS complex and atrial fibrillation as covariates.p-value: <0.000195% CI: [0.473, 0.702]Cox proportional hazard model
Secondary
Number of Participants With First Occurrence Of Heart Failure (HF) Mortality or Heart Failure (HF) Hospitalization (Adjudicated)
Death due to HF or first occurrence of HF hospitalization. Hospitalization due to HF is defined as an overnight stay, or longer, in a hospital environment (emergency room, observation unit or in-patient care, or similar facility including admission to a day care facility) due to HF as the primary reason for hospitalization as determined by the endpoint committee adjudicator.
Time frame: Baseline (30 March 2006) up to 50 months (cut-off date: 25 May 2010), 59.5 months (complete DB phase: 18 March 2011)
Population: FAS using ITT principle: All randomized participants, followed for mortality and other major endpoints for the duration of the double blind treatment period, regardless of compliance with the study drug and the protocol. Here n signifies participants evaluated at that time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Eplerenone: Double-blind Phase | Number of Participants With First Occurrence Of Heart Failure (HF) Mortality or Heart Failure (HF) Hospitalization (Adjudicated) | Up to 50 months (cut-off) (n= 1364, 1373) | 170 participants |
| Eplerenone: Double-blind Phase | Number of Participants With First Occurrence Of Heart Failure (HF) Mortality or Heart Failure (HF) Hospitalization (Adjudicated) | Up to 59.5 months (complete DB) (n= 1367, 1376) | 194 participants |
| Placebo: Double-blind Phase | Number of Participants With First Occurrence Of Heart Failure (HF) Mortality or Heart Failure (HF) Hospitalization (Adjudicated) | Up to 50 months (cut-off) (n= 1364, 1373) | 262 participants |
| Placebo: Double-blind Phase | Number of Participants With First Occurrence Of Heart Failure (HF) Mortality or Heart Failure (HF) Hospitalization (Adjudicated) | Up to 59.5 months (complete DB) (n= 1367, 1376) | 287 participants |
Comparison: The statistical analysis was only performed on the adjudicated endpoint data up to cut-off. Cox proportional hazard model includes treatment as the major factor, adjusting for age, estimated glomerular filtration rate, left ventricular ejection fraction, body mass index, hemoglobin, heart rate, systolic blood pressure, diabetes, history of hypertension, prior myocardial infarction, baseline left bundle branch block, QRS complex and atrial fibrillation as covariates.p-value: <0.000195% CI: [0.475, 0.701]Cox proportional hazard model
Secondary
Number of Participants With First Occurrence of Hospitalization Due to Hyperkalemia (Adjudicated)
First occurrence of hospitalization due to hyperkalemia. Hospitalization due to hyperkalemia is defined as an overnight stay, or longer, in a hospital environment (emergency room, observation unit or in-patient care, or similar facility including admission to a day care facility) due to hyperkalemia as the primary reason for hospitalization as determined by endpoint committee adjudicator. Hyperkalemia is defined as serum potassium level greater than (\>) 5.5 milliequivalents per liter (mEq/L).
Time frame: Baseline (30 March 2006) up to 50 months (cut-off date: 25 May 2010), 59.5 months (complete DB phase: 18 March 2011)
Population: FAS using ITT principle: All randomized participants, followed for mortality and other major endpoints for the duration of the double blind treatment period, regardless of compliance with the study drug and the protocol. Here n signifies participants evaluated at that time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Eplerenone: Double-blind Phase | Number of Participants With First Occurrence of Hospitalization Due to Hyperkalemia (Adjudicated) | Up to 50 months (cut-off) (n= 1364, 1373) | 4 participants |
| Eplerenone: Double-blind Phase | Number of Participants With First Occurrence of Hospitalization Due to Hyperkalemia (Adjudicated) | Up to 59.5 months (complete DB) (n= 1367, 1376) | 4 participants |
| Placebo: Double-blind Phase | Number of Participants With First Occurrence of Hospitalization Due to Hyperkalemia (Adjudicated) | Up to 50 months (cut-off) (n= 1364, 1373) | 3 participants |
| Placebo: Double-blind Phase | Number of Participants With First Occurrence of Hospitalization Due to Hyperkalemia (Adjudicated) | Up to 59.5 months (complete DB) (n= 1367, 1376) | 3 participants |
Comparison: The statistical analysis was only performed on the adjudicated endpoint data up to cut-off. Cox proportional hazard model includes treatment as the major factor, adjusting for age, estimated glomerular filtration rate, left ventricular ejection fraction, body mass index, hemoglobin, heart rate, systolic blood pressure, diabetes, history of hypertension, prior myocardial infarction, baseline left bundle branch block, QRS complex and atrial fibrillation as covariates.p-value: 0.853995% CI: [0.251, 5.312]Cox proportional hazard model
Secondary
Number of Participants With First Occurrence of Hospitalization Due to Worsening Renal Function (Adjudicated)
First occurrence of hospitalization due to worsening renal function. Hospitalization due to worsening renal function is defined as an overnight stay, or longer, in a hospital environment (emergency room, observation unit or in-patient care, or similar facility including admission to a day care facility) due to worsening renal function as the primary reason for hospitalization as determined by endpoint committee adjudicator. Worsening renal function is defined as doubling of serum creatinine level from baseline level.
Time frame: Baseline (30 March 2006) up to 50 months (cut-off date: 25 May 2010), 59.5 months (complete DB phase: 18 March 2011)
Population: FAS using ITT principle: All randomized participants, followed for mortality and other major endpoints for the duration of the double blind treatment period, regardless of compliance with the study drug and the protocol. Here n signifies participants evaluated at that time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Eplerenone: Double-blind Phase | Number of Participants With First Occurrence of Hospitalization Due to Worsening Renal Function (Adjudicated) | Up to 50 months (cut-off) (n= 1364, 1373) | 9 participants |
| Eplerenone: Double-blind Phase | Number of Participants With First Occurrence of Hospitalization Due to Worsening Renal Function (Adjudicated) | Up to 59.5 months (complete DB) (n= 1367, 1376) | 10 participants |
| Placebo: Double-blind Phase | Number of Participants With First Occurrence of Hospitalization Due to Worsening Renal Function (Adjudicated) | Up to 50 months (cut-off) (n= 1364, 1373) | 8 participants |
| Placebo: Double-blind Phase | Number of Participants With First Occurrence of Hospitalization Due to Worsening Renal Function (Adjudicated) | Up to 59.5 months (complete DB) (n= 1367, 1376) | 10 participants |
Comparison: The statistical analysis was only performed on the adjudicated endpoint data up to cut-off. Cox proportional hazard model includes treatment as the major factor, adjusting for age, estimated glomerular filtration rate, left ventricular ejection fraction, body mass index, hemoglobin, heart rate, systolic blood pressure, diabetes, history of hypertension, prior myocardial infarction, baseline left bundle branch block, QRS complex and atrial fibrillation as covariates.p-value: 0.953795% CI: [0.366, 2.578]Cox proportional hazard model
Secondary
Number of Participants With First Occurrence of Implantation of Cardiac Defibrillator (ICD) (Adjudicated)
First occurrence of implantation of cardiac defibrillator (ICD). ICD is an electronic device capable of monitoring the heart rhythm. When the heart is beating normally, the device remains inactive. If the heart develops a life-threatening tachycardia, the ICD delivers electrical shocks to the heart to terminate the abnormal rhythm and return the heart rhythm to normal.
Time frame: Baseline (30 March 2006) up to 50 months (cut-off date: 25 May 2010), 59.5 months (complete DB phase: 18 March 2011)
Population: FAS using ITT principle: All randomized participants, followed for mortality and other major endpoints for the duration of the double blind treatment period, regardless of compliance with the study drug and the protocol. Here n signifies participants evaluated at that time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Eplerenone: Double-blind Phase | Number of Participants With First Occurrence of Implantation of Cardiac Defibrillator (ICD) (Adjudicated) | Up to 50 months (cut-off) (n= 1364, 1373) | 61 participants |
| Eplerenone: Double-blind Phase | Number of Participants With First Occurrence of Implantation of Cardiac Defibrillator (ICD) (Adjudicated) | Up to 59.5 months (complete DB) (n= 1367, 1376) | 76 participants |
| Placebo: Double-blind Phase | Number of Participants With First Occurrence of Implantation of Cardiac Defibrillator (ICD) (Adjudicated) | Up to 50 months (cut-off) (n= 1364, 1373) | 59 participants |
| Placebo: Double-blind Phase | Number of Participants With First Occurrence of Implantation of Cardiac Defibrillator (ICD) (Adjudicated) | Up to 59.5 months (complete DB) (n= 1367, 1376) | 78 participants |
Comparison: The statistical analysis was only performed on the adjudicated endpoint data up to cut-off. Cox proportional hazard model includes treatment as the major factor, adjusting for age, estimated glomerular filtration rate, left ventricular ejection fraction, body mass index, hemoglobin, heart rate, systolic blood pressure, diabetes, history of hypertension, prior myocardial infarction, baseline left bundle branch block, QRS complex and atrial fibrillation as covariates.p-value: 0.975495% CI: [0.694, 1.424]Cox proportional hazard model
Secondary
Number of Participants With First Occurrence of Implantation of Resynchronization Device (Cardiac Resynchronization Therapy [CRT]) (Adjudicated)
First occurrence of implantation of resynchronization device. CRT is use of a specialized pacemaker to re-coordinate the action of the right and left ventricles in heart failure.
Time frame: Baseline (30 March 2006) up to 50 months (cut-off date: 25 May 2010), 59.5 months (complete DB phase: 18 March 2011)
Population: FAS using ITT principle: All randomized participants, followed for mortality and other major endpoints for the duration of the double blind treatment period, regardless of compliance with the study drug and the protocol. Here n signifies participants evaluated at that time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Eplerenone: Double-blind Phase | Number of Participants With First Occurrence of Implantation of Resynchronization Device (Cardiac Resynchronization Therapy [CRT]) (Adjudicated) | Up to 50 months (cut-off) (n= 1364, 1373) | 33 participants |
| Eplerenone: Double-blind Phase | Number of Participants With First Occurrence of Implantation of Resynchronization Device (Cardiac Resynchronization Therapy [CRT]) (Adjudicated) | Up to 59.5 months (complete DB) (n= 1367, 1376) | 45 participants |
| Placebo: Double-blind Phase | Number of Participants With First Occurrence of Implantation of Resynchronization Device (Cardiac Resynchronization Therapy [CRT]) (Adjudicated) | Up to 50 months (cut-off) (n= 1364, 1373) | 41 participants |
| Placebo: Double-blind Phase | Number of Participants With First Occurrence of Implantation of Resynchronization Device (Cardiac Resynchronization Therapy [CRT]) (Adjudicated) | Up to 59.5 months (complete DB) (n= 1367, 1376) | 53 participants |
Comparison: The statistical analysis was only performed on the adjudicated endpoint data up to cut-off. Cox proportional hazard model includes treatment as the major factor, adjusting for age, estimated glomerular filtration rate, left ventricular ejection fraction, body mass index, hemoglobin, heart rate, systolic blood pressure, diabetes, history of hypertension, prior myocardial infarction, baseline left bundle branch block, QRS complex and atrial fibrillation as covariates.p-value: 0.265295% CI: [0.485, 1.22]Cox proportional hazard model
Secondary
Number of Participants With New Onset Atrial Fibrillation or Flutter
New onset of atrial fibrillation or flutter is defined as the diagnosis of atrial fibrillation or flutter in a participant after randomization, where atrial fibrillation was not present before randomization.
Time frame: Baseline (30 March 2006) up to 50 months (cut-off date: 25 May 2010), 59.5 months (complete DB phase: 18 March 2011)
Population: FAS using ITT principle: Here 'N' (Number of Participants Analyzed) signifies those who did not report a history of atrial fibrillation at baseline and n signifies participants evaluated at that time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Eplerenone: Double-blind Phase | Number of Participants With New Onset Atrial Fibrillation or Flutter | Up to 50 months (cut-off) (n= 950, 937) | 32 participants |
| Eplerenone: Double-blind Phase | Number of Participants With New Onset Atrial Fibrillation or Flutter | Up to 59.5 months (complete DB) (n= 956, 940) | 41 participants |
| Placebo: Double-blind Phase | Number of Participants With New Onset Atrial Fibrillation or Flutter | Up to 50 months (cut-off) (n= 950, 937) | 52 participants |
| Placebo: Double-blind Phase | Number of Participants With New Onset Atrial Fibrillation or Flutter | Up to 59.5 months (complete DB) (n= 956, 940) | 59 participants |
Comparison: The statistical analysis was only performed on the adjudicated endpoint data up to cut-off. Cox proportional hazard model includes treatment as the major factor, adjusting for age, estimated glomerular filtration rate, left ventricular ejection fraction, body mass index, hemoglobin, heart rate, systolic blood pressure, diabetes, history of hypertension, prior myocardial infarction, baseline left bundle branch block, QRS complex and atrial fibrillation as covariates.p-value: 0.017595% CI: [0.376, 0.91]Cox proportional hazard model
Secondary
Number of Participants With New Onset Diabetes Mellitus (DM)
The definition of new onset diabetes mellitus is the diagnosis of diabetes mellitus in a participant after randomization, when DM was not present before randomization.
Time frame: Baseline (30 March 2006) up to 50 months (cut-off date: 25 May 2010), 59.5 months (complete DB phase: 18 March 2011)
Population: FAS using ITT principle: Here 'N' (Number of Participants Analyzed) signifies those who did not report a history of diabetes mellitus at baseline and n signifies participants evaluated at that time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Eplerenone: Double-blind Phase | Number of Participants With New Onset Diabetes Mellitus (DM) | Up to 50 months (cut-off) (n= 904, 973) | 34 participants |
| Eplerenone: Double-blind Phase | Number of Participants With New Onset Diabetes Mellitus (DM) | Up to 59.5 months (complete DB) (n= 907, 975) | 42 participants |
| Placebo: Double-blind Phase | Number of Participants With New Onset Diabetes Mellitus (DM) | Up to 59.5 months (complete DB) (n= 907, 975) | 47 participants |
| Placebo: Double-blind Phase | Number of Participants With New Onset Diabetes Mellitus (DM) | Up to 50 months (cut-off) (n= 904, 973) | 40 participants |
Comparison: The statistical analysis was only performed on the adjudicated endpoint data up to cut-off. Cox proportional hazard model includes treatment as the major factor, adjusting for age, estimated glomerular filtration rate, left ventricular ejection fraction, body mass index, hemoglobin, heart rate, systolic blood pressure, diabetes, history of hypertension, prior myocardial infarction, baseline left bundle branch block, QRS complex and atrial fibrillation as covariates.p-value: 0.600995% CI: [0.559, 1.4]Cox proportional hazard model