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.
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.