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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

University of Iceland, Reykjavik, Iceland, cardiac{at}simnet.is

Myron H Weinberger

Indiana University School of Medicine, Indianapolis, IN, USA, MaisonneuveRosemont Hospital, Montreal, Quebec, Canada

Christian M Constance

Indiana University School of Medicine, Indianapolis, IN, USA, MaisonneuveRosemont Hospital, Montreal, Quebec, Canada

Mohammed A Ali

Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA

James Jin

Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA

Margaret F Prescott

Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA

Deborah L Keefe

Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA

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.

Key Words: ACE inhibitor • aliskiren • direct renin inhibitor • diuretic • hydrochlorothiazide • hypertension • ramipril • renin

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This version was published on September 1, 2009

Journal of Renin-Angiotensin-Aldosterone System, Vol. 10, No. 3, 157-167 (2009)
DOI: 10.1177/1470320309342407


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This Article Abstract Free Full Text (Free PDF) Free Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Scopus Google Scholar Articles by Andersen, K. Articles by Keefe, D. L PubMed PubMed Citation Articles by Andersen, K. Articles by Keefe, D. L Social Bookmarking                         What's this?