Additive beneficial effects of Losartan combined with simvastatin in the treatment of hypercholesterolemic, hypertensive patients

Background - Biological mechanisms underlying statin and angiotensin II type 1 receptor blocker therapies differ. Therefore, we compared vascular and metabolic responses to these therapies either alone or in combination in hypercholesterolemic, hypertensive patients. Methods and Results - This was a randomized, double-blind, placebo-controlled crossover trial with 3 treatment arms ( each 2 months) and 2 washout periods ( each 2 months). Forty-seven hypertensive, hypercholesterolemic patients were given simvastatin 20 mg and placebo, simvastatin 20 mg and losartan 100 mg, or losartan 100 mg and placebo daily during each 2-month treatment period. Losartan alone or combined therapy significantly reduced blood pressure compared with simvastatin alone. Compared with losartan alone, simvastatin alone or combined therapy significantly changed lipoproteins. All 3 treatment arms significantly improved flow-mediated dilator response to hyperemia and decreased plasma malondialdehyde and monocyte chemoattractant protein-1 levels relative to baseline measurements. However, these parameters were changed to a greater extent with combined therapy compared with simvastatin or losartan alone ( both P < 0.001 and P = 0.030 for monocyte chemoattractant protein-1 by ANOVA). Combined therapy or losartan alone significantly increased plasma adiponectin levels and insulin sensitivity ( determined by QUICKI) relative to baseline measurements. These changes were significantly greater than in the group treated with simvastatin alone ( P < 0.001 for adiponectin, P = 0.029 for QUICKI by ANOVA). Conclusions - Simvastatin combined with losartan improves endothelial function and reduces inflammatory markers to a greater extent than monotherapy with either drug in hypercholesterolemic, hypertensive patients.