Combination pravastatin and valsartan treatment has additive beneficial effects to simultaneously improve both metabolic and cardiovascular phenotypes beyond that of monotherapy with either drug in patients with primary hypercholesterolemia

Abstract

Statin and angiotensin II type 1 receptor blocker therapy improves endothelial dysfunction using distinct mechanisms. We evaluated simultaneous vascular and metabolic responses to pravastatin and valsartan therapy, alone or in combination, in hypercholesterolemic patients. Forty-eight hypercholesterolemic patients (23 had metabolic syndrome) were given pravastatin 40 mg and placebo, pravastatin 40 mg and valsartan 160 mg, or valsartan 160 mg and placebo daily during each 2-month treatment period in a randomized, single-blind, placebo-controlled, crossover trial with three treatment arms and two washout periods (each 2 months). Brachial artery flow-mediated dilation and C-reactive protein improved to a greater extent with combined therapy compared with either monotherapy. Importantly, we also observed simultaneous improvement in metabolic phenotypes, with all three treatments causing increased plasma adiponectin levels, reduced fasting insulin levels, and increased insulin sensitivity relative to baseline measurements. For the first time in a statin combination trial, pravastatin combined with valsartan therapy increased plasma adiponectin, lowered fasting insulin levels, and improved insulin sensitivity in an additive manner when compared with monotherapy alone. In contrast to other statins, hydrophilic pavastatin may be combined with other drugs to safely reach lipid target levels while simultaneously improving the metabolic and cardiovascular phenotype of patients at high risk.

Trial registration: ClinicalTrials.gov NCT01004237.

Figures

FIG. 1.

Percent change in flow-mediated dilation (left) and percent change in hsCRP levels (right) from respective pretreatment values after treatment with pravastatin alone, combined therapy, and valsartan alone (the median was zero for valsartan). Mean with SEM (left) or median (right) values are provided.

FIG. 2.

Percent change in adiponectin levels (A), percent change in insulin levels (B), and percent change in QUICKI (C) from respective pretreatment values after treatment with pravastatin alone, combined therapy, and valsartan alone. Median values (A and B) or mean with SEM (C) are provided.