Cardiovascular risk reduction: what do recent trials with rosuvastatin tell us?Adv Ther 2009; 26(5):469-87AT
Abundant evidence from large-scale clinical trials supports the importance of lowering low-density lipoprotein cholesterol (LDL-C) to decrease the risk of cardiovascular disease (CVD) events. The LDL-C targets in various guidelines remain important treatment goals but, even in trials where statin therapy achieves substantial reduction of LDL-C, a significant number of CVD events still occur and the residual risk remains high. These findings suggest that lipid parameters other than LDL-C, such as high-density lipoprotein cholesterol (HDL-C), triglycerides, and LDL particle size, can influence the risk of CVD. On this basis, other strategies that can alter the lipid profile, in particular raising HDL.C, may provide additional benefits. Other factors such as HDL-C functionality and susceptibility to oxidation and inflammatory factors can also influence cardiovascular risk. In addition to the modifications of the lipid profile, statins have cholesterol-independent beneficial pleiotropic effects. The contribution of these effects to event reduction is not yet fully understood. Recently, the body of evidence has expanded to support the use of intensive statin therapy in broader patient populations. The JUPITER trial has shown the benefit of intensive statin treatment in low-risk subjects with high levels of high-sensitivity C-reactive protein and average levels of LDL-C. Unlike the setting of primary and secondary prevention, the results of statin trials in patients with heart failure have shown no clear benefit in terms of survival. The recently published AURORA trial was carried out to investigate the effect of rosuvastatin in patients with end-stage renal disease undergoing chronic hemodialysis. In this trial no benefit on cardiovascular events was shown with statin therapy. In conclusion, large outcomes trials have clearly shown that statin treatments have a favorable benefit/risk profile in a large range of patients at different levels of risk, with the exception of patients with heart failure and those with renal disease undergoing dialysis. Further evidence is needed on the role of therapeutic strategies on the so-called residual risk.