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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

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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