Cardiovascular disease is the leading cause of death in industrialized countries. The prevention of cardiovascular disease is critically dependent on lipid lowering therapy, which includes the 3-hydroxymethyl-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins). Although statins are the most prescribed class of drugs worldwide, and therapy is generally associated with a reduction in risk for cardiovascular events by 20-30%, clinical response can be highly variable and adverse effects occur in a minority of patients.
Recent research has provided evidence that in many cases, genetic variation contributes to this variable drug response. Research efforts should be made in analyzing the differences in genetic background to identify which genetic variation accounts for the variability in clinical response. Here we present a study that will establish in a large prospective randomized clinical trial with statin allocation which genetic variation is responsible for the variation in drug response. In 5804 participants of the PROspective Study of Pravastatin in the Elderly at risk (PROSPER) we will perform a genome-wide scan to assess the genetic variation responsible for variation in lowering low-density lipoprotein levels, in clinical outcome and for the occurrence of adverse effects.
The unique character of the PROSPER study is that the study is randomized in three European countries, therefore all associations can be replicated in these countries. Positive associations will be confirmed in two comparable large clinical trials, the WOSCOPS and the CARE study. Cardiovascular pharmacogenomics will lead to improvements in the use of personalized therapy based on an individual's genetic make-up. Non-responders or subjects who experience adverse effects will not be indicated for statin treatment when they are identified.