Combination treatment with troglitazone, an insulin action enhancer, and pravastatin, an inhibitor of HMG-CoA reductase, shows synergistic effect on atherosclerosis of WHHL rabbits

We examined whether improving insulin resistance augments the antiatheroscl erotic effect of LDL reduction. Since WHHL rabbits show hyperinsulinemia an d insulin resistance, we administered troglitazone (100 mg/kg), an insulin action enhancer, pravastatin sodium (50 mg/kg), an HMG-CoA reductase inhibi tor, and a combination of both drugs to 2-month-old WHHL rabbits for 32 wee ks. As compared to the control, total cholesterol levels in the plasma and LDL were decreased significantly by approximate to 20% in the pravastatin a nd combination groups. Basal immunoreactive insulin levels and insulin inde x were decreased significantly by approximate to 50% in the troglitazone an d combination groups. Surface lesion area of atherosclerosis on the thoraci c aorta was decreased significantly by 36% in the combination group and was less in the troglitazone group. Coronary atherosclerosis was decreased sig nificantly by 39% in the combination group and was less in the pravastatin and troglitazone groups. The collagen content in the plaques was decreased in the troglitezone and combination groups and the extracellular lipid depo sits were decreased in the pravastatin and combination groups. The incidenc e and severity of xanthomata in the digital joints were also decreased sign ificantly in the three treated groups. In conclusion, the antiatherogenic e ffect of the combination treatment is stronger than that of the monotherapy . (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.