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

摘要

Objective: We aimed to investigate whether the single pill combination (SPC) of aliskiren 300mg and amlodipine 10mg (ALIS 300/AMLO 10) improves blood pressure (BP) reduction in hypertensive patients not adequately controlled by the SPC olmesartan 40mg and amlodipine 10mg (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) 12.5mg was added. EudraCT 2009-016693-33. Results: In the 342 patients treated, OLM 40/AMLO 10 reduced systolic BP (SBP)/diastolic BP (DBP) by 24.5/14.5mmHg 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 5.1mmHg (95% confidence interval [CI] 3.7 to 6.5, p<0.0001) and a DBP reduction of 4.8mmHg (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 12.5mg decreased SBP/DBP by further 8.1/6.7mmHg (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.