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Aliskiren, an oral renin inhibitor, in hypertensive patients - Aliskiren, an oral renin inhibitor, in hypertensive patients
Description:
The goal of the trial was to evaluate the safety and the antihypertensive effect of treatment with aliskiren, a novel oral renin inhibitor, compared with placebo in hypertensive patients.
Study Design
Study Design:
Patients Enrolled: 652
Mean Follow Up: Eight weeks
Mean Patient Age: Mean age 56 years
Female: 50
Patient Populations:
Age ≥18 years, and mild to moderate essential hypertension (mean sitting DBP ≥95 mm Hg and <110 mm Hg)
Exclusions:
Severe hypertension (mean sitting DBP ≥110 mm Hg or SBP ≥180 mm Hg); secondary hypertension; type 1 diabetes or type 2 diabetes with poor glucose control; history of cardiovascular disease; history of malignancy or other life-threatening disease; and any medical or surgical condition that might significantly alter the absorption, distribution, metabolism, or excretion of study drugs
Primary Endpoints:
Change from baseline in trough mean sitting DBP
Drug/Procedures Used:
Following a two-week placebo run-in phase, patients were randomized to once-daily oral doses of aliskiren 150 mg (n=127), aliskiren 300 mg (n=130), aliskiren 600 mg (n=130), irbesartan 150 mg (n=134), or placebo (n=131). Follow-up visits were performed at weeks 2, 4, 6, and 8. Three sitting blood pressure measurements were taken at each visit and the average was used for the analysis.
Principal Findings:
Baseline characteristics were well balanced between the treatment groups. Average blood pressure was 152/99 mm Hg. Study drug was discontinued prior to study completion in 66 patients, with no difference by treatment group.
The reduction in both systolic blood pressure (SBP) and diastolic blood pressure (DBP) was significantly greater at follow-up in all three aliskiren dose groups compared to placebo (least squares mean reduction in DBP 9.3, 11.8, and 11.5 mm Hg for 150 mg, 300 mg, and 600 mg, respectively, vs. 6.3 mm Hg for placebo; reduction in SBP 11.4, 15.8, and 15.7 mm Hg vs. 5.3 mm Hg; all p<0.001).
There was a dose-dependent reduction (p<0.001) up to 300 mg, but not additional reduction with 600 mg. Both SBP and DBP were also reduced with irbesartan 150 mg compared with placebo (DBP 8.9 mm Hg and SBP 12.5 mm Hg, p<0.05 vs. placebo). The reduction in blood pressure in the aliskiren 150 group did not differ from the irbesartan 150 mg group (p=NS), but the aliskiren 300 mg and 600 mg group had significantly larger reductions than the irbesartan 150 mg group (p<0.05).
The endpoint of controlled blood pressure was met in more patients in the irbesartan 150 mg group (33.8%) and the aliskiren 150 mg (37.8%), 300 mg (50.0%), and 600 mg (45.7%) than in the placebo group (20.8%; p<0.05 for each comparison). Additionally, the aliskiren 300 mg and 600 mg group reductions were greater than the irbesartan group (p<0.05). Adverse events were similar between treatment groups.
Interpretation:
Among patients with mild to moderate hypertension, once-daily treatment with the novel oral renin inhibitor aliskiren was associated with a greater reduction in both SBP and DBP compared with placebo. Additionally, aliskiren 300 mg and 600 mg were associated with greater reductions in blood pressure compared with irbesartan. The safety profile was similar between treatment groups.
References:
Gradman AH, Schmieder RE, Lins RL, Nussberger J, Chiang Y, Bedigian MP. Aliskiren, a novel orally effective renin inhibitor, provides dose-dependent antihypertensive efficacy and placebo-like tolerability in hypertensive patients. Circulation 2005;111:1012-8.
Keywords: Biphenyl Compounds, Fumarates, Renin, Blood Pressure, Tetrazoles, Hypertension, Least-Squares Analysis
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