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Effects of the direct renin inhibitor aliskiren and atenolol alone or in combination in patients with hypertension1

Charité Universitätsmedizin, Berlin, Germany

Ralf Dechend

Franz Volhard Clinic, Berlin, Germany

Chuek-Man Yu

Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong

Manesh Bheda

Novartis Pharma AG, Basel, Switzerland

Jessica Ford

Novartis Pharma AG, Basel, Switzerland

Margaret F. Prescott

Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA

Deborah L. Keefe

Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA, deborah.keefe{at}novartis.com

Introduction. Aliskiren is the first in a new class of direct renin inhibitors to be approved for the treatment of hypertension.

Patients and methods. In this double-blind, multicentre trial, 694 patients with hypertension (mean sitting diastolic blood pressure [BP] 95 and < 110 mmHg) were randomised to once-daily aliskiren 150 mg (n=231), atenolol 50 mg (n=231) or the combination (150/50 mg; n=232) for six weeks, followed by a further six weeks on double the initial doses of aliskiren and atenolol. Efficacy (reduction from baseline in mean sitting systolic and diastolic BP) and tolerability of study treatments were assessed; plasma renin activity (PRA) was measured in a subset of patients.

Results. At Week 12 endpoint, aliskiren, atenolol and aliskiren/atenolol lowered systolic and diastolic BP from baseline by 14.3/11.3, 14.3/13.7 and 17.3/14.1 mmHg, respectively. Systolic BP reductions with aliskiren/atenolol were significantly greater than those with aliskiren (p=0.039) or atenolol (p=0.034) alone, and diastolic BP reductions were greater than with aliskiren alone (p<0.001). Diastolic BP changes were larger with atenolol than with aliskiren (p=0.003, correlating with the large reductions in pulse rate (> 10 bpm) observed with atenolol. Aliskiren, atenolol and aliskiren/atenolol reduced geometric mean PRA from baseline by 65%, 52% and 61%, respectively. In patients with moderate or high baseline PRA ( 0.65 ng/ml/hour), PRA was reduced to low levels (< 0.65 ng/ml/hour) at Week 12 endpoint in a greater proportion of patients receiving aliskiren (11/15 patients, 73.3%) or aliskiren/atenolol (18/23, 78.3%) than with atenolol (10/21, 47.6%). Aliskiren treatment was associated with numerically lower rates of adverse events and discontinuations due to adverse events compared with atenolol or combination treatment, and unlike atenolol was not associated with bradycardia.

Conclusions. Direct renin inhibition with aliskiren may be an appropriate substitute for beta-blocker treatment in patients with uncomplicated hypertension. Aliskiren also represents an attractive option for dual therapy with atenolol to improve systolic BP/pulse pressure reductions and BP control with maintained tolerability compared with atenolol alone.

Key Words: aliskiren • beta-blocker • plasma renin activity • pulse pressure • renin-angiotensin system

Journal of Renin-Angiotensin-Aldosterone System, Vol. 9, No. 3, 163-175 (2008)
DOI: 10.1177/1470320308096411


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