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.