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Renin inhibition with aliskiren provides additive antihypertensive efficacy when used in combination with hydrochlorothiazide.
J Hypertens. 2007 Jan; 25(1):217-26.JH

Abstract

OBJECTIVES

Aliskiren is a novel, orally active renin inhibitor. Its antihypertensive efficacy and safety, alone and in combination with hydrochlorothiazide (HCTZ), were investigated in an 8-week, double-blind, placebo-controlled trial in hypertensive patients. The effects of these treatments on plasma renin activity (PRA) were also assessed.

METHODS

A total of 2776 patients aged >or=18 years with mean sitting diastolic blood pressure (MSDBP) 95-109 mmHg were randomized to receive once-daily treatment with aliskiren (75, 150 or 300 mg), HCTZ (6.25, 12.5 or 25 mg), the combination of aliskiren and HCTZ, or placebo, in a factorial design. The primary endpoint was the change in MSDBP from baseline to week 8. PRA was assessed at these timepoints at selected study centers.

RESULTS

Aliskiren monotherapy was superior to placebo (P < 0.001; overall Dunnett's test) in reducing MSDBP and mean sitting systolic blood pressure (MSSBP). Combination treatment was superior to both component monotherapies in reducing BP (maximum MSSBP/MSDBP reduction of 21.2/14.3 mmHg from baseline with aliskiren/HCTZ 300/25 mg), and resulted in more responders (patients with MSDBP < 90 mmHg and/or >or=10 mmHg reduction) and better control rates (patients achieving MSSBP/MSDBP < 140/90 mmHg) than either monotherapy. Aliskiren monotherapy reduced PRA by up to 65% from baseline. Although HCTZ monotherapy increased PRA by up to 72%, PRA decreased in all of the combination therapy groups. All active treatments were well tolerated.

CONCLUSIONS

Aliskiren monotherapy demonstrated significant BP lowering, and its effect was considerably greater when combined with HCTZ. Renin inhibition with aliskiren neutralized the compensatory rise in PRA induced by HCTZ.

Authors+Show Affiliations

Fundapres, Las-Heras 2910-Piso 1A, Buenos Aires, Argentina. asvillamil@intramed.netNo 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

Language

eng

PubMed ID

17143194

Citation

Villamil, Alberto, et al. "Renin Inhibition With Aliskiren Provides Additive Antihypertensive Efficacy when Used in Combination With Hydrochlorothiazide." Journal of Hypertension, vol. 25, no. 1, 2007, pp. 217-26.
Villamil A, Chrysant SG, Calhoun D, et al. Renin inhibition with aliskiren provides additive antihypertensive efficacy when used in combination with hydrochlorothiazide. J Hypertens. 2007;25(1):217-26.
Villamil, A., Chrysant, S. G., Calhoun, D., Schober, B., Hsu, H., Matrisciano-Dimichino, L., & Zhang, J. (2007). Renin inhibition with aliskiren provides additive antihypertensive efficacy when used in combination with hydrochlorothiazide. Journal of Hypertension, 25(1), 217-26.
Villamil A, et al. Renin Inhibition With Aliskiren Provides Additive Antihypertensive Efficacy when Used in Combination With Hydrochlorothiazide. J Hypertens. 2007;25(1):217-26. PubMed PMID: 17143194.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Renin inhibition with aliskiren provides additive antihypertensive efficacy when used in combination with hydrochlorothiazide. AU - Villamil,Alberto, AU - Chrysant,Steven G, AU - Calhoun,David, AU - Schober,Bonnie, AU - Hsu,Huang, AU - Matrisciano-Dimichino,Linda, AU - Zhang,Jack, PY - 2006/12/5/pubmed PY - 2007/3/3/medline PY - 2006/12/5/entrez SP - 217 EP - 26 JF - Journal of hypertension JO - J. Hypertens. VL - 25 IS - 1 N2 - OBJECTIVES: Aliskiren is a novel, orally active renin inhibitor. Its antihypertensive efficacy and safety, alone and in combination with hydrochlorothiazide (HCTZ), were investigated in an 8-week, double-blind, placebo-controlled trial in hypertensive patients. The effects of these treatments on plasma renin activity (PRA) were also assessed. METHODS: A total of 2776 patients aged >or=18 years with mean sitting diastolic blood pressure (MSDBP) 95-109 mmHg were randomized to receive once-daily treatment with aliskiren (75, 150 or 300 mg), HCTZ (6.25, 12.5 or 25 mg), the combination of aliskiren and HCTZ, or placebo, in a factorial design. The primary endpoint was the change in MSDBP from baseline to week 8. PRA was assessed at these timepoints at selected study centers. RESULTS: Aliskiren monotherapy was superior to placebo (P < 0.001; overall Dunnett's test) in reducing MSDBP and mean sitting systolic blood pressure (MSSBP). Combination treatment was superior to both component monotherapies in reducing BP (maximum MSSBP/MSDBP reduction of 21.2/14.3 mmHg from baseline with aliskiren/HCTZ 300/25 mg), and resulted in more responders (patients with MSDBP < 90 mmHg and/or >or=10 mmHg reduction) and better control rates (patients achieving MSSBP/MSDBP < 140/90 mmHg) than either monotherapy. Aliskiren monotherapy reduced PRA by up to 65% from baseline. Although HCTZ monotherapy increased PRA by up to 72%, PRA decreased in all of the combination therapy groups. All active treatments were well tolerated. CONCLUSIONS: Aliskiren monotherapy demonstrated significant BP lowering, and its effect was considerably greater when combined with HCTZ. Renin inhibition with aliskiren neutralized the compensatory rise in PRA induced by HCTZ. SN - 0263-6352 UR - https://www.unboundmedicine.com/medline/citation/17143194/Renin_inhibition_with_aliskiren_provides_additive_antihypertensive_efficacy_when_used_in_combination_with_hydrochlorothiazide_ L2 - http://dx.doi.org/10.1097/HJH.0b013e3280103a6b DB - PRIME DP - Unbound Medicine ER -