, Volume 26, Issue 11, pp 1012-1023

Amlodipine/valsartan/hydrochlorothiazide triple combination therapy in moderate/severe hypertension: Secondary analyses evaluating efficacy and safety

Abstract

Introduction

An 8-week trial of amlodipine/valsartan/hydrochlorothiazide (Aml/Val/HCTZ) for moderate or severe hypertension demonstrated more-pronounced blood pressure (BP)-lowering effects compared with dual-component therapies. To elucidate the effects of time and baseline BP on the observed responses, exploratory analyses were performed.

Methods

Patients aged 18–85 years with mean sitting systolic BP (MSSBP) 145 to <200 mmHg and mean sitting diastolic BP (MSDBP) 100 to <120 mmHg were randomized to Aml 10 mg/Val 320 mg/HCTZ 25 mg; Val 320 mg/HCTZ 25 mg; Aml 10 mg/Val 320 mg; or Aml 10 mg/HCTZ 25 mg. During the first 2 weeks, regimens were force-titrated in two stages.

Results

All least-square mean reductions in MSSBP and MSDBP (baseline to Week 3 and end of study) were significantly greater with triple therapy than with each dual therapy in the overall population and the severe systolic subgroup (baseline MSSBP ≥180 mmHg; except vs. Aml 10 mg/Val 320 mg at Week 3). At Week 3, more patients on triple therapy achieved MSSBP reductions of ≥−60, ≥−50, ≥−40, ≥−30, and ≥−20 mmHg (2.5%, 9.7%, 23.2%, 46.9% and 74.5%, respectively) than those on dual therapy (1.1%–2%, 5.6%–5.9%, 14.5%–16.7%, 33.5%–39.1%, and 58.8%–65.5%, respectively); this was also true at study endpoint. End-of-study MSSBP reductions were greater in triple-therapy recipients who had higher (vs. lower) baseline MSSBPs. LSM reductions ranged from −27.2 mmHg for baseline MSSBP 145 to <150 mmHg, to ≥49.6 mmHg for baseline MSSBP ≥180 mmHg. All treatments were well tolerated regardless of baseline MSSBP.

Conclusion

Aml 10 mg/Val 320 mg/HCTZ 25 mg triple therapy is highly effective in reducing BP compared with dual components early in therapy, and systolic BP-lowering effects were proportionate to hypertension severity.