Key result
The combination of olmesartan and pravastatin produced a greater reduction in aortic surface lesion area, lesional thickness, and cholesterol content than either drug alone in hyperlipidemic rabbits.
Why the study?
Does the combination of olmesartan and pravastatin reduce atherosclerosis compared to monotherapy in genetically hyperlipidemic rabbits?
Does the combination of olmesartan and pravastatin reduce atherosclerosis compared to monotherapy in genetically hyperlipidemic rabbits?
Coadministration of an ARB and a statin produces a greater antiatherogenic effect than either monotherapy in a hyperlipidemic rabbit model.
Caution against clinical adoption; leaves open whether ARB-statin synergy reduces human atherosclerosis.
The purpose of this study was to examine whether coadministration of olmesartan medoxomil (OLM), an AT1 subtype specific angiotensin II receptor blocker (ARB), and pravastatin (PRV), a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, could enhance the antiatherogenic effect compared with monotherapy. Vehicle, PRV (25 mg/kg), OLM (0.5 mg/kg), and PRV (25 mg/kg) and OLM (0.5 mg/kg) in combination were administered to Watanabe heritable hyperlipidemic (WHHL) rabbits for 8 months. OLM alone and in combination lowered blood pressure to a similar degree, whereas PRV alone had no effect. PRV alone and in combination lowered blood cholesterol to a similar degree, whereas OLM alone had no effect. The combination of PRV and OLM decreased effectively both surface lesion area and lesional thickness in aortic tissue, producing a greater reduction in aortic cholesterol content than either drug alone. Immunohistological examination of the aorta revealed that PRV reduced macrophage infiltration and lipid deposition and that OLM reduced macrophage infiltration accompanied by reduction in monocyte chemoattractant protein-1 expression and N-(carboxymethyl)lysine protein adduct, an oxidative stress marker. It is concluded that OLM, an ARB, and PRV, an HMG-CoA reductase inhibitor, in combination produce a greater antiatherogenic effect than monotherapy via the combination of the different antiatherosclerotic mechanisms of each drug.
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Kato et al. (2005) studied Atherosclerosis. Olmesartan medoxomil and pravastatin combination vs. Vehicle, PRV alone, OLM alone was evaluated on Surface lesion area, lesional thickness, and aortic cholesterol content. The combination of olmesartan and pravastatin produced a greater reduction in aortic surface lesion area, lesional thickness, and cholesterol content than either drug alone in hyperlipidemic rabbits.
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