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Comparative effects of aliskiren-based and ramipril-based therapy on the renin system during long-term (6 months) treatment and withdrawal in patients with hypertension.
J Renin Angiotensin Aldosterone Syst. 2009 Sep; 10(3):157-67.JR

Abstract

INTRODUCTION

This subgroup analysis assessed the effects of treatment based on the direct renin inhibitor, aliskiren, or the angiotensin-converting enzyme inhibitor, ramipril, on plasma renin activity (PRA), plasma renin concentration (PRC) and other biomarkers in a 26-week randomised, double-blind trial. Changes in PRA and PRC after stopping treatment were also assessed.

METHODS

After placebo run-in, 842 patients (mean sitting diastolic blood pressure (BP) 95-109 mmHg) were randomised to aliskiren 150 mg or ramipril 5 mg. Dose titration and hydrochlorothiazide addition were allowed after Week 6 and 12, respectively, for inadequate BP control. Patients completing active treatment were re-randomised to current regimen or placebo during a 4-week posttreatment phase.

RESULTS

BP reductions were independent of baseline PRA at Week 12, were greater with aliskiren- than ramipril-based therapy at Week 26 (17.9/13.3 vs. 15.2/12.0 mmHg, p<0.05) and persisted for longer after stopping aliskiren. Aliskiren-based therapy reduced geometric mean PRA (-63%, p<0.05; n=103), while ramipril-based therapy increased PRA (+143%, p<0.05; n=100) at Week 26; PRC increased in both groups (aliskiren: +224% [n=33], ramipril: +145% [n=39], both p<0.05). Four weeks after stopping aliskiren-based therapy, PRA remained 52% below pre-treatment baseline; PRA returned to baseline 2 weeks after stopping ramipril-based therapy.

CONCLUSIONS

Aliskiren-based therapy produced sustained BP and PRA reductions over 26 weeks; ramipril-based therapy lowered BP and increased PRA. PRA reductions persisted 4 weeks after stopping aliskiren, suggesting an inhibitory effect beyond the elimination half-life of the drug.

Authors+Show Affiliations

Department of Medicine, Division of Cardiology, University of Iceland, Reykjavik, Iceland. cardiac@simnet.isNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19617271

Citation

Andersen, Karl, et al. "Comparative Effects of Aliskiren-based and Ramipril-based Therapy On the Renin System During Long-term (6 Months) Treatment and Withdrawal in Patients With Hypertension." Journal of the Renin-angiotensin-aldosterone System : JRAAS, vol. 10, no. 3, 2009, pp. 157-67.
Andersen K, Weinberger MH, Constance CM, et al. Comparative effects of aliskiren-based and ramipril-based therapy on the renin system during long-term (6 months) treatment and withdrawal in patients with hypertension. J Renin Angiotensin Aldosterone Syst. 2009;10(3):157-67.
Andersen, K., Weinberger, M. H., Constance, C. M., Ali, M. A., Jin, J., Prescott, M. F., & Keefe, D. L. (2009). Comparative effects of aliskiren-based and ramipril-based therapy on the renin system during long-term (6 months) treatment and withdrawal in patients with hypertension. Journal of the Renin-angiotensin-aldosterone System : JRAAS, 10(3), 157-67. https://doi.org/10.1177/1470320309342407
Andersen K, et al. Comparative Effects of Aliskiren-based and Ramipril-based Therapy On the Renin System During Long-term (6 Months) Treatment and Withdrawal in Patients With Hypertension. J Renin Angiotensin Aldosterone Syst. 2009;10(3):157-67. PubMed PMID: 19617271.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Comparative effects of aliskiren-based and ramipril-based therapy on the renin system during long-term (6 months) treatment and withdrawal in patients with hypertension. AU - Andersen,Karl, AU - Weinberger,Myron H, AU - Constance,Christian M, AU - Ali,Mohammed A, AU - Jin,James, AU - Prescott,Margaret F, AU - Keefe,Deborah L, Y1 - 2009/07/17/ PY - 2009/7/21/entrez PY - 2009/7/21/pubmed PY - 2010/2/4/medline SP - 157 EP - 67 JF - Journal of the renin-angiotensin-aldosterone system : JRAAS JO - J Renin Angiotensin Aldosterone Syst VL - 10 IS - 3 N2 - INTRODUCTION: This subgroup analysis assessed the effects of treatment based on the direct renin inhibitor, aliskiren, or the angiotensin-converting enzyme inhibitor, ramipril, on plasma renin activity (PRA), plasma renin concentration (PRC) and other biomarkers in a 26-week randomised, double-blind trial. Changes in PRA and PRC after stopping treatment were also assessed. METHODS: After placebo run-in, 842 patients (mean sitting diastolic blood pressure (BP) 95-109 mmHg) were randomised to aliskiren 150 mg or ramipril 5 mg. Dose titration and hydrochlorothiazide addition were allowed after Week 6 and 12, respectively, for inadequate BP control. Patients completing active treatment were re-randomised to current regimen or placebo during a 4-week posttreatment phase. RESULTS: BP reductions were independent of baseline PRA at Week 12, were greater with aliskiren- than ramipril-based therapy at Week 26 (17.9/13.3 vs. 15.2/12.0 mmHg, p<0.05) and persisted for longer after stopping aliskiren. Aliskiren-based therapy reduced geometric mean PRA (-63%, p<0.05; n=103), while ramipril-based therapy increased PRA (+143%, p<0.05; n=100) at Week 26; PRC increased in both groups (aliskiren: +224% [n=33], ramipril: +145% [n=39], both p<0.05). Four weeks after stopping aliskiren-based therapy, PRA remained 52% below pre-treatment baseline; PRA returned to baseline 2 weeks after stopping ramipril-based therapy. CONCLUSIONS: Aliskiren-based therapy produced sustained BP and PRA reductions over 26 weeks; ramipril-based therapy lowered BP and increased PRA. PRA reductions persisted 4 weeks after stopping aliskiren, suggesting an inhibitory effect beyond the elimination half-life of the drug. SN - 1752-8976 UR - https://www.unboundmedicine.com/medline/citation/19617271/Comparative_effects_of_aliskiren_based_and_ramipril_based_therapy_on_the_renin_system_during_long_term__6_months__treatment_and_withdrawal_in_patients_with_hypertension_ L2 - https://journals.sagepub.com/doi/10.1177/1470320309342407?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -