Efficacy and tolerability of the single-pill combination of aliskiren 300 mg/amlodipine 10 mg in hypertensive patients not controlled by olmesartan 40 mg/amlodipine 10 mg

Abstract

Objective:

We aimed to investigate whether the single pill combination (SPC) of aliskiren 300 mg and amlodipine 10 mg (ALIS 300/AMLO 10) improves blood pressure (BP) reduction in hypertensive patients not adequately controlled by the SPC olmesartan 40 mg and amlodipine 10 mg (OLM 40/AMLO 10).

Methods:

Open-label, non-randomized single-arm study. Patients with stage 2 hypertension were titrated to the SPC OLM 40/AMLO 10 (4-week Phase 1). If hypertension was not controlled they were switched to the SPC ALIS 300/AMLO 10 (4-week Phase 2). In the optional 4-week study extension hydrochlorothiazide (HCT) 12.5 mg was added. EudraCT 2009-016693-33.

Results:

In the 342 patients treated, OLM 40/AMLO 10 reduced systolic BP (SBP)/diastolic BP (DBP) by 24.5/14.5 mmHg by end of Phase 1. Those 187 patients with uncontrolled hypertension at the end of Phase 1 switched to ALIS 300/AMLO 10 experienced a further SBP reduction of 5.1 mmHg (95% confidence interval [CI] 3.7 to 6.5, p < 0.0001) and a DBP reduction of 4.8 mmHg (95% CI 3.8 to 5.8; p < 0.0001) in Phase 2. DBP or SBP responder rates were achieved by 51.3% or 44.4%, respectively, SBP and DBP normalization by 36.4%. In 65 patients whose BP was not controlled in Phase 2, SPC ALIS 300/AMLO 10/HCT 12.5 mg decreased SBP/DBP by further 8.1/6.7 mmHg (p < 0.0001 each). No deaths or serious adverse events were noted. Significant adverse events leading to study discontinuation were reported in 2.6% (Phase 1), 2.7% (Phase 2), and 0% (extension). Limitations included the open-label, single-arm non-randomized design, and the relatively short duration.

Conclusions:

In this switch study reflecting clinical practice, patients with moderate hypertension not controlled by the SPC OLM 40/AMLO 10 achieved a clinically and statistically significant reduction of blood pressure from the SPC ALIS 300/AMLO 10 and the optional addition of HCT. All drug combinations were well tolerated.

Key words::

• Aliskiren
• Amlodipine
• Arterial hypertension
• Combination therapy
• Hydrochlorothiazide
• Olmesartan

Transparency

Declaration of funding

The study was funded by Novartis Pharma GmbH.

Declaration of financial/other relationships

C.A. has disclosed that he has no relevant financial relationships to disclose. C.S., F.M. and E.K. have disclosed that they are employees of Novartis Pharma GmbH Germany.

Peer reviewer 1 has disclosed that he has no relevant financial relationships. Peer reviewer 2 has disclosed that he has been a consultant on hypertensive medications to numerous pharmaceutical companies, including Daiichi Sankyo, Novartis, Sanofi Aventis, Bayer, Actelion and Berlin-Chemie.

Acknowledgments

We acknowledge the cooperation and commitment of all investigators and their staff, who made the present trial possible.

The results of this study were presented at the Annual Meeting of the German Society for Internal Medicine (DGIM), 30 April to 4 May 2011, Wiesbaden, Germany and at the Annual Meeting of the European Society of Hypertension (ESH), 17–20 June 2011.

Notes

* Sevikar is a registered trade name of Daiichi Sankyo, Tokyo, Japan.

† Rasilamlo is a registered trade name of Novartis, Basel, Switzerland.

‡ Amturnide is a registered trade name of Novartis, East Hanover, NJ, USA.

* Azor is a registered tradename of Daiichi Sankyo Inc., Parsippany, New Jersey, USA.