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Plasma renin and the antihypertensive effect of the orally active renin inhibitor aliskiren in clinical hypertension.
Int J Clin Pract. 2007 Sep; 61(9):1461-8.IJ

Abstract

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).

Authors+Show Affiliations

Department of Internal Medicine, CHUV, Lausanne, Switzerland. Juerg.Nussberger@chuv.chNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial, Phase II
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17590217

Citation

Nussberger, J, et al. "Plasma Renin and the Antihypertensive Effect of the Orally Active Renin Inhibitor Aliskiren in Clinical Hypertension." International Journal of Clinical Practice, vol. 61, no. 9, 2007, pp. 1461-8.
Nussberger J, Gradman AH, Schmieder RE, et al. Plasma renin and the antihypertensive effect of the orally active renin inhibitor aliskiren in clinical hypertension. Int J Clin Pract. 2007;61(9):1461-8.
Nussberger, J., Gradman, A. H., Schmieder, R. E., Lins, R. L., Chiang, Y., & Prescott, M. F. (2007). Plasma renin and the antihypertensive effect of the orally active renin inhibitor aliskiren in clinical hypertension. International Journal of Clinical Practice, 61(9), 1461-8.
Nussberger J, et al. Plasma Renin and the Antihypertensive Effect of the Orally Active Renin Inhibitor Aliskiren in Clinical Hypertension. Int J Clin Pract. 2007;61(9):1461-8. PubMed PMID: 17590217.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Plasma renin and the antihypertensive effect of the orally active renin inhibitor aliskiren in clinical hypertension. AU - Nussberger,J, AU - Gradman,A H, AU - Schmieder,R E, AU - Lins,R L, AU - Chiang,Y, AU - Prescott,M F, Y1 - 2007/06/22/ PY - 2007/6/26/pubmed PY - 2007/11/1/medline PY - 2007/6/26/entrez SP - 1461 EP - 8 JF - International journal of clinical practice JO - Int J Clin Pract VL - 61 IS - 9 N2 - 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). SN - 1368-5031 UR - https://www.unboundmedicine.com/medline/citation/17590217/Plasma_renin_and_the_antihypertensive_effect_of_the_orally_active_renin_inhibitor_aliskiren_in_clinical_hypertension_ L2 - https://doi.org/10.1111/j.1742-1241.2007.01473.x DB - PRIME DP - Unbound Medicine ER -