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Aliskiren and valsartan for antihypertensive therapy - Aliskiren and valsartan for antihypertensive therapy – Presented at ACC 2007
Description:
The goal of the trial was to evaluate treatment with aliskiren, valsartan, or the combination of the two compared with placebo among patients with mild to moderate hypertension.
Study Design
Study Design:
Patients Enrolled: 1,797
Mean Follow Up: 8 weeks
Mean Patient Age: Mean age, 52 years
Female: 39
Patient Populations:
DBP >95 and <110 mm Hg
Primary Endpoints:
Reduction in mean sitting DBP
Secondary Endpoints:
Reduction in mean sitting SBP, response rate, and achievement of blood pressure control (<140/90 mm Hg)
Drug/Procedures Used:
Following a 1- to 2-week period of washout from prior hypertensive therapy and a run-in period of 3-4 weeks, patients were randomized in a double-blind manner to aliskiren (150 mg; n = 437), valsartan (160 mg; n = 455), the combination of the two (n = 446), or placebo (n = 459). Treatment was to continue for 4 weeks, at which time the doses were doubled for the following 4 weeks. Blood pressure was evaluated at baseline, 4 weeks, and 8 weeks.
Principal Findings:
Mean blood pressure at baseline was 154/100 mm Hg. At 8-week follow-up, diastolic blood pressure (DBP) declined by 4.1 mm Hg in the placebo group, 9.0 mm Hg in the aliskiren group, 9.7 mm Hg in the valsartan group, and 12.2 mm Hg in the combination group (p < 0.001 for combination vs. placebo and for combination vs. each individually). Likewise, systolic blood pressure (SBP) declined by 4.6 mm Hg in the placebo group, 13.0 mm Hg in the aliskiren group, 12.8 mm Hg in the valsartan group, and 17.2 mm Hg in the combination group (p < 0.001 for combination vs. placebo and for combination vs. each individually). Blood pressure response rate was highest in the combination group (66% vs. 30% for placebo, 53% for aliskiren, and 55% for valsartan; p < 0.05 for combination vs. placebo and for combination vs. each individually), as was blood pressure control (49% vs. 16% for placebo, 37% for aliskiren, and 34% for valsartan).
Adverse events occurred with similar frequency between groups (37% in the placebo group, 34% in the aliskiren group, 37% in the valsartan group, and 35% in the combination group).
Interpretation:
Among patients with mild to moderate hypertension, aliskiren, valsartan, and the combination of the two were associated with greater reductions in blood pressure compared with placebo at 8 weeks, with the largest reductions seen in the combination group.
Both aliskiren and valsartan are inhibitors of the renin-angiotensin-aldosterone system, but act at different points in the system, with aliskiren acting at the point of activation. Both agents were effective in reducing blood pressure, but the combination of the two agents appeared to be additive. The editorial published with the manuscript highlights several limiations of the study, including the low rate of patients who were randomized into the trial among those screened (45%), the slightly higher but overall low rate of transient hyperkalemia in the combination group, and the choice of the combined therapy arm, which used aliskiren with valsartan rather than with a diuretic or calcium-channel blocker.
References:
Oparil S, et al. Efficacy and safety of combined use of aliskiren and valsartan in patients with hypertension: a randomised, double-blind trial. Lancet 2007; 370: 221–29.
Presented by Dr. Suzanne Oparil at the American College of Cardiology Annual Scientific Session, New Orleans, LA, March 2007.
Keywords: Fumarates, Angiotensin II Type 1 Receptor Blockers, Diuretics, Renin-Angiotensin System, Hyperkalemia, Blood Pressure, Valine, Tetrazoles, Hypertension
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