Efficacy and tolerability of aliskiren 300 mg/hydrochlorothiazide 25 mg (±amlodipine 5 mg) in hypertensive patients not controlled by candesartan 32 mg plus HCT 25 mg

Abstract

Aims:

The majority of patients with essential hypertension of moderate severity (WHO grade 2) require combination therapy. We aimed to investigate whether the single-pill combination of aliskiren 300 mg and hydrochlorothiazide (HCT) 25 mg (ALIS 300/HCT 25) improves the BP reduction in hypertensive patients not adequately controlled by the free combination of candesartan 32 mg and HCT 25 mg (CAN 32 + HCT 25).

Methods:

In an open-label, single-arm study, patients with mean sitting diastolic blood pressure (DBP) between 100–109 mmHg at baseline received 4-week treatment with CAN 32 + HCT 25 (Phase 1), followed – in patients whose BP was not controlled – by 4-week treatment with ALIS 300/HCT 25 (Phase 2). The DBP change between weeks 4 and 8 was the primary endpoint. The ClinicalTrials.gov Identifier is NCT00867490.

Results:

In the 186 patients treated, CAN 32 + HCT 25 reduced systolic BP (SBP)/DBP by 18.9/12.2 mmHg. Those 123 patients with uncontrolled hypertension switched to ALIS 300/HCT 25 experienced a further SBP/DBP reduction of 2.8/3.1 mmHg between week 4 and week 8 (p = 0.0064 and p < 0.0001), and 33.3% achieved DBP normalisation. In 61 patients not controlled after week 8 (SBP ≥ 140 mmHg or DBP ≥ 90 mmHg), who participated in an optional study extension, amlodipine 5 mg was added. Triple therapy over 4 weeks decreased SBP/DBP by further 9.2/5.9 mmHg (p < 0.0001 each). Adverse events with suspected drug relationship were noted in 4.3% (Phase 1), 3.3% (Phase 2), and 1.6% (extension) of the patients. Limitations of the study include the open-label, non-randomised approach and short treatment duration across the individual phases.

Conclusions:

In this open-label, single-arm switch study reflecting clinical practice, patients with moderate hypertension not controlled by the free combination of CAN 32 + HCT 25 achieved a clinically and statistically significant reduction of blood pressure from the single pill combination of ALIS 300/HCT 25, and the optional addition of amlodipine.

Trial registration: ClinicalTrials.gov identifier: NCT00867490.

Key words::

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

Transparency

Declaration of funding

The study was funded by Novartis Pharma GmbH.

Declaration of financial/other relationships

J.S. has disclosed that he has no conflicts of interest. S.K. has disclosed that he is an employee of Novartis. H.J.U. and H.B. declare that they have no financial interests related to this study.

Acknowledgements

The authors acknowledge the cooperation and commitment of all investigators and their staff, who made the present trial possible. We are indebted to Ch. Sieder for his statistical work, and to Prof. Dr David Pittrow, Institute for Clinical Pharmacology, TU Dresden, for input to the interpretation of the results.

These results were presented at the 20th European Meeting on Hypertension of the European Society of Hypertension (ESH, Oslo, Norway, 18–21 June 2010) and the 116th Congress of the German Society of Internal Medicine (DGIM, Wiesbaden, Germany, 10–14 April 2010).