Abstract 178: Byvalson Fixed-Dose Combination for the Treatment of Hypertension

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Abstract

Purpose: Byvalson (nebivolol and valsartan), FDA approved in June 2016 for the treatment of hypertension, is the first combination beta blocker and ARB fixed-dose combination medication available. Two-thirds of patients with hypertension require more than one drug to achieve BP control. The combination of two antihypertensive medications has been associated with greater BP control, compliance, and reduced adverse effects. Nebivolol is a highly selective β1-adrenergic receptor antagonist with vasodilator properties and valsartan is an ARB. The objective of this study is to evaluate clinical efficacy and safety of this combination of BP-lowering medications in the treatment of hypertension.

Methods: A comprehensive literature search was conducted to date utilizing MEDLINE and PUBMED with the following search terms: “nebivolol”, “valsartan”, and “hypertension” to retrieve clinical trials. The following three studies were found: a phase I randomized, open-label study investigating pharmacokinetic and pharmacodynamic interactions between nebivolol and valsartan; and two phase III studies evaluating the safety and efficacy of combination treatment: one is an open-label, single-arm study over 52 weeks and the other is a phase III randomized, placebo-controlled study comparing fixed-dose combination to nebivolol and valsartan alone over 8 weeks. Analysis of the study designs, methods, results, statistical analyses, and conclusions were properly conducted for appropriateness and validity.

Results: The pharmacokinetic and pharmacodynamics parameters in the phase I study involving 30 patients had statistically significant steady-state PK interactions deemed not clinically significant, significant reductions in blood pressure (p≤0.005) and other PD interactions. A phase III trial (n=4161) showed significantly greater reductions from baseline at 8 weeks in DBP in the fixed-dose combination group than both nebivolol 40 mg (mean difference –1.2 mm Hg [95% CI, –2.3 to –0.1; p=0.030] and valsartan 320 mg (–4.4 mm Hg [95% CI, –5.4 to –3.3]; p<0.0001). SBP reductions were also significant (p<0.01). Another phase III trial (n=810) showed significant reductions from baseline at 52 weeks for SBP (-25.5±15.9 mm Hg) and for DBP (-19.0±8.7 mm Hg). 75.7% of nebivolol/valsartan and 57.8% of nebivolol/valsartan/HCTZ patients achieved a BP goal of <140/90.

Conclusion: Both phase III trials evaluating the combination treatment of nebivolol and valsartan demonstrated long term safety, efficacy, and tolerability with significant reductions in systolic and diastolic blood pressure compared with monotherapy. The phase I study showed limited PK interactions, additive PD effects, and tolerability in healthy volunteers. As an initial therapy in patients with inadequately controlled blood pressure, Byvalson 5/80 mg taken orally once daily is a safe and effective treatment for the hypertension.

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