Abstract 1637: Effect of Simvastatin 20 and 80 mg/day on Vascular Function and Structure in CHD Patients with Familial Hypercholesterolaemia. Final Results of the ESCAPE Study
The main objective of the ESCAPE study was to investigate the effect of long-term treatment of patients with CHD and familial hypercholesterolaemia (FH) with simvastatin 20 and 80 mg/day on endothelial function, distensibility, stiffness of a common carotid artery and cross-sectional area of atherosclerotic plaques (CSA, mm2). Fifty FH patients were randomized for treatment with open-label simvastatin 80 mg/day (group A, n=26) or 20 mg/day (group B, n=24) for 76 weeks. Patients visited the lipid clinic at weeks 6, 12, 28, 40, 52, 64 and 76 to determine lipid levels, liver enzymes, creatine kinase (CK) and to assess flow-mediated vasodilatation (FMD), distensibilty coefficient (DC) and stiffness (index β) of a common carotid artery.
Methods. Endothelial function (FMD) of the brachial artery and CSA was determined using high resolution ultrasound with ACUSON 128XP/10. DC and stiffness parameters were calculated using standard mathematical formulas.
Findings. Forty FH patients completed the study. Mean LDL-C reduction in group A was 45.5%, in group B - 35,2%. FMD increased in group A by 49% (p<0.01) at week 12 and by 44 % (p<0.05) at week 28. FMD increased at week 12 (group B)by 39% (ns) and at week 28 by 56% (p<0.01). Mean CSA in group A increased by 5% at week 76 (ns), in group B - increased by 17% by week 76 (p<0.01). Treatment with simvastatin 20 and 80 mg/day was well tolerated. Two pts had side-effects (elevation of CK and unstable angina).
Conclusion. Long-term treatment with simvasatin 80 mg/day in FH pts can significantly improve FMD after 12 weeks, DC and stiffness after 52 weeks. Moderate LDL-C reduction (−35%) in FH pts with simvastatin 20 mg/day may also improve FMD within 28 weeks, DC at 52 weeks, and arterial stiffness after 76 weeks of treatment. Agressive treatment with simvastatin 80 mg/day may retard the progression of atherosclerotic plaques in carotid arteries.