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Effects of the direct renin inhibitor aliskiren and atenolol alone or in combination in patients with hypertension.
J Renin Angiotensin Aldosterone Syst. 2008 Sep; 9(3):163-75.JR

Abstract

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] > or = 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 (> or = 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.

Authors+Show Affiliations

Charité Universitätsmedizin, Berlin, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

18957387

Citation

Dietz, Rainer, et al. "Effects of the Direct Renin Inhibitor Aliskiren and Atenolol Alone or in Combination in Patients With Hypertension." Journal of the Renin-angiotensin-aldosterone System : JRAAS, vol. 9, no. 3, 2008, pp. 163-75.
Dietz R, Dechend R, Yu CM, et al. Effects of the direct renin inhibitor aliskiren and atenolol alone or in combination in patients with hypertension. J Renin Angiotensin Aldosterone Syst. 2008;9(3):163-75.
Dietz, R., Dechend, R., Yu, C. M., Bheda, M., Ford, J., Prescott, M. F., & Keefe, D. L. (2008). Effects of the direct renin inhibitor aliskiren and atenolol alone or in combination in patients with hypertension. Journal of the Renin-angiotensin-aldosterone System : JRAAS, 9(3), 163-75. https://doi.org/10.1177/1470320308096411
Dietz R, et al. Effects of the Direct Renin Inhibitor Aliskiren and Atenolol Alone or in Combination in Patients With Hypertension. J Renin Angiotensin Aldosterone Syst. 2008;9(3):163-75. PubMed PMID: 18957387.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of the direct renin inhibitor aliskiren and atenolol alone or in combination in patients with hypertension. AU - Dietz,Rainer, AU - Dechend,Ralf, AU - Yu,Chuek-Man, AU - Bheda,Manesh, AU - Ford,Jessica, AU - Prescott,Margaret F, AU - Keefe,Deborah L, PY - 2008/10/30/pubmed PY - 2010/1/14/medline PY - 2008/10/30/entrez SP - 163 EP - 75 JF - Journal of the renin-angiotensin-aldosterone system : JRAAS JO - J Renin Angiotensin Aldosterone Syst VL - 9 IS - 3 N2 - 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] > or = 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 (> or = 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. SN - 1752-8976 UR - https://www.unboundmedicine.com/medline/citation/18957387/Effects_of_the_direct_renin_inhibitor_aliskiren_and_atenolol_alone_or_in_combination_in_patients_with_hypertension_ L2 - https://journals.sagepub.com/doi/10.1177/1470320308096411?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -