The role of HMG-CoA reductase inhibitors in cardiovascular risk reduction
Guidelines on CHD prevention have placed emphasis on identifying and treating suitable individuals with statin therapy and have set cholesterol goals to be attained. Absolute risk is based on modifiable and non-modifiable factors including age. By failing to initiate statin treatment in high risk patients at a younger age, a large proportion of cardiovascular risk will accumulate. Modifiable risk identifies individuals in addition to the patients selected using absolute risk. The additional patients identified were younger with similar modifiable risk factors. Modifiable risk is cost effective but by initiating treatment at a younger age the benefits would increase as the number of event free years would increase. It is recommended total cholesterol should be reduced to <5.0mmol/l. In this study 54.6% failed this goal and this group had a greater proportion of females, primary prevention, were younger, greater TC but with lower efficacy. 43% of those who failed target responded appropriately. The remaining 57% did not respond sufficiently to the statin dose. Only 56.0% claimed in a questionnaire to fully comply with their statin. Those who admitted to poor compliance were younger and had a reduced TC efficacy. Of the study population 13.4% did not have a detectable level of simvastatin or simvastatin acid in their plasma and this was supported by the difference in TC reduction observed. It has been proposed that CYP2D6 is involved in the metabolism of simvastatin acid. Five individuals were found to carry more than one copy of the CYP2D6 gene and were fast metabolisers. This did not correlate with a reduced efficacy therefore it is unlikely CYP2D6 metabolises simvastatin acid. This study has identified factors which contribute to the failure of over half of patients prescribed statin to achieve target and by doing so treatment can be tailored to achieve maximal cholesterol lowering efficacy.