Clinical study of the month. REVERAL and PROVE-IT: confirmation of the concept the lower, the better" for cholesterol therapy in patients with coronary heart disease"

peer reviewedStatins, as compared to placebo, have proven their efficacy in reducing cardiovascular events in patients with or without cardiovascular disease and in a large range of cholesterol levels. Two new head-to-head randomised trials comparing intensive treatment with atorvastatin 80 mg/day with moderate treatment with pravastatin 40 mg/day were recently completed. The mechanistic "Reversing Atherosclerosis with Aggressive Lipid Lowering" (REVERSAL) trial randomised 502 patients with stable coronary disease. Atorvastatin 80 mg (leading to a mean LDL cholesterol of 79 mg/dl) was superior to pravastatin 40 mg (mean LDL of 110 mg/dl) in terms of limiting the progression of atheroma assessed with the use of intravascular ultrasonography after 18 months of follow up (p = 0.02). These differences may be related to the greater reduction in atherogenic lipoprotein (-46% versus -26%, p < 0.001) and C-reactive protein (-36% versus -5%, p < 0.001) in patients treated with atorvastatin as compared to pravastatin. In the clinical "Pravastatin or Atorvastatin Evaluation and Infection Therapy" (PROVE-IT) trial, 4162 patients with acute coronary syndromes were randomised to either atorvastatin 80 mg or pravastatin 40 mg and followed for a mean of 24 months. Again, atorvastatin (mean LDL of 62 mg/dl) was superior to pravastatin (mean LDL of 95 mg/dl), resulting in a 16% percent lower risk of the primary end point, a composite of major cardiovascular events (p = 0.005). Thus, both REVERSAL and PROVE-IT support the concept "the lower, the better". However, they do not allow to disentangle the independent and interdependent effects of statins on LDL cholesterol and the process of arterial inflammation. What so ever, the results suggest that the target LDL cholesterol level may be lower than recommended in the current guidelines in high-risk patient so that a sea change in the prevention and management of atherosclerotic vascular disease may occur very soon