Achieving BP goals with valsartan and HCTZ alone and in combination: pooled analysis of two randomized, double-blind, placebo-controlled studies

ABSTRACT

Background: Most patients with hypertension will require combination therapy to achieve blood pressure (BP) goals, especially the elderly, obese, or those with stage 2 hypertension.

Objective: To assess BP response and time to achieve BP goals in a diverse population of hypertensive patients treated with hydrochlorothiazide, valsartan, or a combination.

Methods: For this secondary post-hoc analysis, data were pooled from two similar randomized, double-blind, 8-week trials that evaluated hydrochlorothiazide (12.5–25 mg) and valsartan (160 mg) monotherapies, their combination (160/12.5 mg), and placebo. Subgroups were defined by age, hypertension severity, and obesity. Adults with diastolic BP ≥ 95 and ≤ 115 mmHg were included. Goal rates were estimated from a logistic model with treatment, study, age group, race, and baseline body mass index as factors and baseline diastolic BP as a covariate. Kaplan–Meier estimates were used to calculate the time to achieve BP goals.

Main outcome measures: Efficacy variables were reductions from baseline to study end in systolic BP and diastolic BP, rates of achieving BP goals (< 140/90 mmHg), and time to achieve BP goals. Adverse events were also reported for the pooled trials.

Results: BP reductions at study end and goal achievement rates were greater with combination therapy (–20/15 mmHg and 72%, respectively) than with either monotherapy (valsartan 160 mg: –14/11 mmHg, 61%; hydrochlorothiazide 25 mg: –14/10 mmHg, 50%) for the overall population (N = 1313) and in patient subgroups. Patients treated with initial combination therapy reached goal in 27–56% of the time needed for those treated with monotherapy. Combination therapy was well tolerated and was associated with a decreased incidence of hypokalemia compared with hydrochlorothiazide monotherapy.

Conclusions: Compared with monotherapy, combination therapy resulted in greater reductions in BP and achievement of goal BP in a shorter period of time. Although interpretation of this study is subject to the limitations associated with any post-hoc analysis, the results suggest that initiating treatment with combination therapy may be considered for expedient and effective BP control.

Key Words::

• Angiotensin receptor blocker
• Combination therapy
• Hypertension
• Pooled analysis
• Thiazide diuretic
• Valsartan

Acknowledgments

Declaration of interest: D.T.N. received an honorarium for his time and effort spent preparing this article. N.C. and D.Z. are employees of Novartis Pharmaceuticals Corporation. The authors thank Wiley Webb of Landmark Programs for providing editorial support funded by Novartis.