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.
BACKGROUND
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.
Andersen
Karl
K
Department of Medicine, Division of Cardiology, University of Iceland, Reykjavik, Iceland. cardiac@simnet.is
Weinberger
Myron H
MH
Constance
Christian M
CM
Ali
Mohammed A
MA
Jin
James
J
Prescott
Margaret F
MF
Keefe
Deborah L
DL
D000419:Albuminuria / Q000097:blood / Q000150:complications; D000577:Amides / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects; D003404:Creatinine / Q000097:blood; D003710:Demography; D003971:Diastole / Q000187:drug effects; D005260:Female; D005650:Fumarates / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use*; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D017257:Ramipril / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use*; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System / Q000187:drug effects*; D013599:Systole / Q000187:drug effects; D013997:Time Factors
D000577:Amides; D000959:Antihypertensive Agents; D015415:Biomarkers; D005650:Fumarates; C446481:aliskiren; D003404:Creatinine; D012083:Renin; D017257:Ramipril