Efficacy of Aliskiren Compared to Ramipril in the Treatment of Moderate Systolic Hypertensive Patients

The arm in which the highest sitting systolic blood pressure (SBP) was found at study entry was used for all subsequent readings. At each study visit, after leaving the patient to rest 5 minutes in a sitting position, the blood pressure (BP) was measured three times with an oscillometric device. The measurements were performed at 1-2 minute intervals. The mean BP was calculated from the 3 readings. The analysis of covariance included treatment factor and baseline mean sitting SBP as covariable.

Time frame: Baseline to 8 weeks

Population: Intent to treat population included all randomized patients who had received at least one dose of study drug. It also excluded all those patients from centers that reported more than 90% of BP measurements rounded to 0 or 5.

The arm in which the highest sitting systolic blood pressure (SBP) was found at study entry was used for all subsequent readings. At each study visit, after leaving the patient to rest 5 minutes in a sitting position, the blood pressure (BP) was measured three times with an oscillometric device. The measurements were performed at 1-2 minute intervals. The mean BP was calculated from the 3 readings. The analysis of variance included treatment factor and baseline value of mean sitting DBP as covariable.

Time frame: Baseline to 8 weeks

Population: Intent to treat population included all randomized patients who had received at least one dose of study drug. It also excluded all those patients from centers that reported more than 90% of BP measurements rounded to 0 or 5. Patients with observation at both time points were included in this analysis.

The sub-groups were: Riser = patients with \>= 55 mmHg difference between the mean SPB measured at the morning surge and the mean minimal SBP measured during the night. The Non-risers in whom the difference is \<55 mmHg. Patients called dippers in whom there was a decrease in average nocturnal SBP ≥ 10% compared with average daytime SBP, in contrast to patients non-dippers in whom this difference was \<10%.

Time frame: Baseline to 8 weeks

Population: Intent to treat population included all randomized patients who had received at least one dose of study drug. It also excluded all those patients from centers that reported more than 90% of BP measurements rounded to 0 or 5. Patients with observation at different categories were included in this analysis.

The change in blood pressure was measured between visit 4 (end of the period of double-blind active treatment which was at week 8) and visit 5 (48 hours after the last active dose taken) in the group of patients who received aliskiren or placebo and those who received ramipril or placebo. The analysis of covariance included treatment factor and baseline mean sitting SBP and mean sitting DBP as covariables.

Time frame: From 8 weeks to 48 hours after week 8

Population: Per-protocol missed dose population included all per protocol population patients who had received the study treatment for period 3 according to the protocol (duration of period 3 and treatment intake). Patients with observation at both time points were included in this analysis.

The arm in which the highest sitting systolic blood pressure (SBP) was found at study entry was used for all subsequent readings. At each study visit, after leaving the patient to rest 5 minutes in a sitting position, the blood pressure (BP) was measured three times with an oscillometric device. The measurements were performed at 1-2 minute intervals. The mean BP was calculated from the 3 readings. The analysis of covariance included treatment factor and baseline mean sitting SBP and mean sitting DBP as covariables.

Time frame: Baseline to 4 weeks

Population: Intent to treat population included all randomized patients who had received at least one dose of study drug. It also excluded all those patients from centers that reported more than 90% of BP measurements rounded to 0 or 5.

Ambulatory blood pressure measurement (ABPM) over 24 hours was performed for all patients on the eve of visit 4 (week 8), the device attached to the ambulatory blood pressure non-dominant arm of the patient. The difference between mean-hour maximum SBP mean-hour minimum SBP between 1 am and 8 am was measured.

Time frame: At week 8

Population: Intent to treat population included all randomized patients who had received at least one dose of study drug. It also excluded all those patients from centers that reported more than 90% of BP measurements rounded to 0 or 5. Patients with ABPM measurements over 24 hours were included in this analysis.

Ambulatory blood pressure measurement (ABPM) over 24 hours was performed for all patients on the day before visit 4, the device attached to the ambulatory blood pressure non-dominant arm of the patient. The BP morning surge was defined as the average of the measurements taken during the first 2 hours after waking the patient. The minimal night blood pressure was defined as the average of the two lowest BP measures (the lowest hourly average) recorded during night time.

Time frame: After 8 weeks

Population: Intent to treat population included all randomized patients who had received at least one dose of study drug. It also excluded all those patients from centers that reported more than 90% of BP measurements rounded to 0 or 5. Patients with ABPM to evaluate the occurrence or absence of a morning peak were included in this analysis.

Adverse events 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: 8 weeks + 1 day

Population: All randomized patients except one patient from Aliskiren arm who was lost to follow up after visit 2.

The arm in which the highest sitting systolic blood pressure (SBP) was found at study entry was used for all subsequent readings. At each study visit, after leaving the patient to rest 5 minutes in a sitting position, the blood pressure (BP) was measured three times with an oscillometric device. The measurements were performed at 1-2 minute intervals. The mean BP was calculated from the 3 readings. Controlled blood pressure (BP) is defined as mean office systolic BP/ diastolic BP \< 140/90 mmHg.

Time frame: At 4 and 8 weeks

Population: Intent to treat population included all randomized patients who had received at least one dose of study drug. It also excluded all those patients from centers that reported more than 90% of BP measurements rounded to 0 or 5. Patients with observation at each time point were included in this analysis.