Long-term safety and efficacy of aliskiren and valsartan combination with or without the addition of HCT in patients with hypertension

Abstract

Objective:

To assess the long-term safety and antihypertensive efficacy of aliskiren/valsartan 300/320 mg combination.

Methods:

This was a 54-week, multicenter, open-label study (core phase), followed by a 26-week extension phase. Efficacy variables were change in msDBP and msSBP from baseline to endpoint (54-week and 80-week). Safety was assessed by monitoring and recording adverse events (AEs). ClinicalTrials.gov Identifier: NCT00386607

Results:

A total of 601 patients (msDBP ≥90 and <110 mmHg) entered the 54-week core study. Optional add-on HCT was allowed at week 10 onwards if BP was ≥140/90 mmHg at two consecutive visits. Of the 486 patients completed the core study, 180 patients entered the extension phase and received aliskiren/valsartan and add-on HCT (12.5 or 25 mg). Overall the combination of aliskiren/valsartan was well-tolerated and the majority of AEs were mild-to-moderate in severity. The incidence of SAEs was low (core phase: n = 22 [3.7%]; extension phase: n = 4 [2.2%]). Elevated serum potassium (>5.5 mmol/L at any time during the study) was observed in 21 (3.6%) patients. The majority of these elevations were transient and returned to normal in subsequent visits, and the discontinuation rate due to elevated serum potassium was low (0.3% [n = 2]). Decreased serum potassium levels (<3.5 mmol/L at any time during the study) was observed in 26 (4.4%) patients, mainly in patients receiving aliskiren/valsartan/HCT (n = 22; 7.1%). At the 54-week endpoint, a mean BP reduction of 20.5/13.4 mmHg from baseline (baseline BP: 152.9/97.0 mmHg) was observed and 66.9% (n = 398/595) of patients achieved BP control with aliskiren/valsartan with or without HCT. At the end of the extension phase (80-week endpoint), additional reduction in BP was obtained (overall, 28.8/18.3 mmHg) and 86.6% (n = 155/179) of patients achieved BP control with aliskiren/valsartan/HCT. A limitation is the absence of an active comparator group.

Conclusion:

Long-term treatment with the combination of aliskiren/valsartan with or without HCT provided clinically meaningful BP reductions and high rates of BP control and was well-tolerated.

Trial registration: ClinicalTrials.gov identifier: NCT00386607.

Key words::

• Aliskiren
• Direct renin inhibition
• Hyperkalemia
• Hypertension
• Valsartan

Transparency

Declaration of funding

This study was funded by Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.

Declaration of financial relationships

S.G.C. has received clinical research grants from Novartis. A.V.M. has received clinical research funds from Novartis and other pharmaceutical companies as a clinical investigator. U.C.H. does not have any conflicts of interest, been in an advisory board for Novartis and received honorarium for talks. D.D. has received honoraria for speaking, C.H.E. assistance, advisory board engagements and grants for the purpose of clinical trials from several pharmaceutical companies. S.P., S.R., and J.Z. are employees of Novartis Pharmaceuticals Corporation. Peer reviewers may receive honoraria from CMRO for their review work. Peer Reviewer 1 has disclosed that he/she is the recipient of research/grant funding from Astra-Zeneca, Merck-Schering-Plough, Sanofi-Aventis, Merck & Co. Inc. and Novartis; is a consultant/advisor to Astra-Zeneca, Bristol Myers Squibb, Gilead, GlaxoSmithKline, Novartis, Sanofi-Aventis, Pfizer, Merck & Co. Inc., Merck-Schering-Plough, LifeCycle Pharma and SurfaceLogix; and is a member of the speakers bureaus for Astra-Zeneca, Bristol Myers Squibb, Gilead, GlaxoSmithKline, Novartis, Sanofi-Aventis, Pfizer, Merck & Co. Inc. and Merck-Schering-Plough. Peer Reviewer 2 has disclosed no relevant financial relationships.

Acknowledgments

This study was supported by Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA. The authors take full responsibility for the content of the paper but thank Shivali Arora, Ashish Agarwal and Thej Kumar Nallagangula of Novartis for assistance in collating and incorporating comments from all authors and editing the final manuscript.

A poster on the results of the core study has previously been presented in 19th European Meeting on Hypertension.