Aliskiren significantly reduced systolic blood pressure (p<0.001 vs placebo) and dose-dependently decreased plasma renin activity by 69-75% (p<0.05 vs placebo) in hypertensive patients.
RCT (n=569)
Double-blind
Does aliskiren reduce blood pressure and alter plasma renin activity compared to placebo or irbesartan in patients with mild-to-moderate hypertension?
Aliskiren effectively reduces systolic blood pressure and plasma renin activity while dose-dependently increasing plasma renin concentration in patients with mild-to-moderate hypertension.
p-value: p=<0.001
BACKGROUND: Aliskiren is the first in a new class of orally effective renin inhibitors for the treatment of hypertension. METHODS: In 569 patients with mild-to-moderate hypertension, blood pressure (BP), plasma renin activity (PRA) and plasma renin concentration (PRC) were measured before and after 8 weeks of double-blind treatment with once-daily oral doses of aliskiren (150, 300 or 600 mg), irbesartan 150 mg or placebo. RESULTS: Aliskiren 150, 300 and 600 mg and irbesartan 150 mg significantly reduced mean cuff sitting systolic BP (SBP) from baseline (p < 0.001 vs. placebo). Aliskiren 150, 300 and 600 mg significantly reduced geometric mean PRA by 69%, 71% and 75% from baseline respectively (p < 0.05 vs. placebo). Irbesartan 150 mg significantly increased PRA by 109% (p < 0.05 vs. placebo). Aliskiren dose-dependently increased PRC from baseline by 157%, 246% and 497%, at 150, 300 and 600 mg respectively, compared with a 9% decrease with placebo (p < 0.05). PRC increased significantly more with aliskiren 300 and 600 mg compared with irbesartan 150 mg (105%; p < 0.05). Regression analysis showed no significant correlations between baseline PRA and changes in SBP in any of the treatment groups, but interestingly, the slopes of the regression lines between changes in SBP and log-transformed baseline PRA were +2.0 for placebo and -1.5, -1.8 and -2.3 for aliskiren 150, 300 and 600 mg respectively. The slope for irbesartan 150 mg (-1.4) was similar to that for aliskiren 150 mg. CONCLUSIONS: Aliskiren reduces SBP and PRA and increases PRC dose-dependently. In contrast, irbesartan reduces SBP but increases both PRC and PRA. As PRA is a measurement of angiotensin I-generating capacity, PRA can be used for measuring the ability of an antihypertensive agent to prevent the generation or action of Ang II, either directly (renin inhibitors, beta-blockers, central alpha(2)-agonists) or indirectly (AT(1)-receptor blockers, ACE inhibitors).
Nussberger et al. (Fri,) conducted a rct in mild-to-moderate hypertension (n=569). Aliskiren vs. Irbesartan 150 mg or placebo was evaluated on mean cuff sitting systolic BP (SBP), plasma renin activity (PRA) and plasma renin concentration (PRC) (p=<0.001). Aliskiren significantly reduced systolic blood pressure (p<0.001 vs placebo) and dose-dependently decreased plasma renin activity by 69-75% (p<0.05 vs placebo) in hypertensive patients.
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