Safety and Efficacy of Aliskiren in Post Myocardial Infarction Patients (ASPIRE)

Change from baseline to end of study in left ventricular end systolic volume (LVESV) as measured by echocardiography. LVESV is a measurement of the volume of blood in the heart's left ventricular chamber at the end of the heart's contraction. This measurement was made by the echocardiography lab. LVESV values between 22 to 58 mL for men and 19-49 mL for women are considered normal. Baseline LVESV was a covariate.

Time frame: Baseline and final visit (after 26 to 36 weeks of treatment)

Population: Echocardiogram evaluable set (patients who had acceptable echocardiogram measurements both at baseline and at post-baseline after receiving at least 26 weeks of treatment)

AEs are defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events are any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgment of investigators represent significant hazards.

Time frame: Extension study (24 weeks)

Population: Extension Population (considered as Safety population) consisting of all enrolled patients who received at least one dose of study medication in the extension study.

Change from baseline to end of study in left ventricular ejection fraction (LVEF) (%) as measured by echocardiography. LVEF is the fraction of blood (in percent) pumped out of the heart's left ventricular chamber with each heart beat, and is a measure of cardiac output for the heart. This measurement was made by the echocardiography lab. Ejection fraction percentages \> 55% are considered normal. Baseline LVEF was a covariate.

Time frame: Baseline and final visit (after 26 to 36 weeks of treatment )

Population: Echocardiogram evaluable set: Patients who had acceptable echocardiogram measurements both at baseline and at post-baseline after receiving at least 26 weeks of treatment.

Change from baseline to end of study in left ventricular end diastolic volume (LVEDV) as measured by echocardiography. (LVEDV) is a measurement of the volume of blood in the heart's left ventricular chamber at the beginning of the chamber's filling with blood. This measurement was made by the echocardiography lab. LVEDV values between 67 to 155 mL for men and 56 to 104 mL for women are considered normal. Baseline LVEDV was a covariate.

Time frame: Baseline and final visit (after 26 to 36 weeks of treatment)

Population: Echocardiogram evaluable set: Patients who had acceptable echocardiogram measurements both at baseline and at post-baseline after receiving at least 26 weeks of treatment.

Change from baseline to end of study in infarction segment length (ISL) (%) as measured by echocardiography. This is the length of the myocardial infarction segment as a percentage of the total cavity perimeter length as calculated by the echocardiography lab. Baseline ISL was a covariate.

Time frame: Baseline and final visit (after 26 to 36 weeks of treatment)

Population: Echocardiogram evaluable set: Patients who had acceptable echocardiogram measurements both at baseline and at post-baseline after receiving at least 26 weeks of treatment.

Change from baseline to end of study in Wall Motion Score (WMS) as measured by echocardiography. WMS was obtained by examining multiple segments of the left ventricle and assigning each segment a score based on myocardial thickening: 1 for normal, 2 for hypokinetic; 3 for akinetic; and 4 for dyskinetic. The WMS was obtained as the average score for the segments visualized and was calculated by the echocardiography lab. Possible values range from 1 to 5. Higher scores are considered worse. Baseline WMS was a covariate.

Time frame: Baseline and final visit (after 26 to 36 weeks of treatment)

Population: Echocardiogram evaluable set: Patients who had acceptable echocardiogram measurements both at baseline and at post-baseline after receiving at least 26 weeks of treatment.

Composite outcome 1 included: Cardiovascular (CV) Death, hospitalization for heart failure (HF), or absolute reduction in Left Ventricular Ejection Fraction (LVEF) greater than 6%. Composite outcome 2 included: CV Death, hospitalization for HF, recurrent Myocardial Infarction, Stroke, or Resuscitated Sudden Death. LVEF was measured at baseline and final visit. All other events were adjudicated by a blinded external committee. Each composite endpoint analysis was based on (a) the percent of patients with that endpoint and (b) days in study to 1st event (or last exposure if no event occurred).

Time frame: LVEF was measured at baseline and at final visit (after 26 to 36 weeks of treatment). Other endpoint components were assessed from randomization until the end of the study (week 36).

Population: Full Analysis Set (FAS) - All randomized patients who either (a) received study drug or (b) did not receive study drug but were not disqualified from randomization.

Change from baseline to Month 12 in left ventricular ejection fraction (LVEF) (%) as measured by echocardiography. LVEF is the fraction of blood (in percent) pumped out of the heart's left ventricular chamber with each heart beat, and is a measure of cardiac output for the heart. This measurement was made by the echocardiography lab. Ejection fraction percentages \> 55% are considered normal.

Time frame: Baseline(extension study), Month 12 (extension study)

Population: Echocardiogram Analysis Set consisting of all patients in the extension population who had acceptable ECHO measurements at extension baseline and Month 12.

Change from baseline to Month 12 in left ventricular end diastolic volume (LVEDV) as measured by echocardiography. LVEDV is a measurement of the volume of blood in the heart's left ventricular chamber at the beginning of the chamber's filling with blood. This measurement was made by the echocardiography lab. LVEDV values between 67 to 155 mL for men and 56 to 104 mL for women are considered normal.

Time frame: Baseline (extension study), Month 12 (extension study)

Population: Echocardiogram Analysis Set consisting of all patients in the extension population who had acceptable ECHO measurements at extension baseline and Month 12.

Change from baseline to Month 12 in left ventricular end systolic volume (LVESV) as measured by echocardiography. LVESV is a measurement of the volume of blood in the heart's left ventricular chamber at the end of the heart's contraction. This measurement was made by the echocardiography lab. LVESV values between 22 to 58 mL for men and 19-49 mL for women are considered normal.

Time frame: Baseline(extension study), Month 12 (extension study)

Population: Echocardiogram Analysis Set consisting of all patients in the extension population who had acceptable ECHO measurements at extension baseline and Month 12.

Orthostatic blood pressure change is defined as a decrease of at least 20 mmHg in systolic blood pressure or a decrease of at least 10 mmHg in diastolic blood pressure when a patient moves from a sitting position to a standing position. A patient could show orthostatic blood pressure change at more than one visit. End of study is Month 24 or early discontinuation.

Time frame: Baseline (Day 0 Extension study), Week 2, Months 1, 3, 6, 9,16, 20, 24

Population: Extension population (considered as Safety population) consisted of all enrolled patients who received at least one dose of study medication in the extension study. n in each of the categories is the number of participants with data available at the given time-point.

Fasting blood samples were collected throughout the study and were analyzed at a central laboratory. Percentage of participants with the following clinically significant laboratory values are reported: Potassium \<3.5 mmol/L; Low value (Normal reference range: 3.5- 5.3) Potassium \>5.5 mmol/L and Potassium \>6.0 mmol/L; High values (Normal reference range: 3.5-5.3) Creatinine \>176.8 μmol/L; High value (Normal reference range= Male: 62- 106 and Female 44- 80) Blood Urea Nitrogen (BUN) \>14.28; High value (Normal reference range: 2.1- 8.9)

Time frame: 24 Months

Population: Extension population (considered as Safety population) consisted of all enrolled patients who received at least one dose of study medication in the extension study. n in each of the categories is the number of participants with data available at the given time-point.