Lipid lowering in patients with chronic kidney disease: a SHARP turn in the wrong direction?

Abstract

The question whether lipid-lowering treatment is associated with a decrease in cardiovascular morbidity and mortality in patients with chronic kidney disease has been disputed for a while, with recent trials in patients on haemodialysis failing to show benefit. Recently, the long-awaited results of the SHARP (Study of Heart And Renal Protection) trial were published. This randomized trial compared the effects of either simvastatin 20 mg plus ezetimibe 10 mg daily or placebo on the occurrence of a first major vascular event in 9720 patients with chronic kidney disease. There was a 17% relative risk reduction but no benefit on survival. We address our concerns regarding the conclusions drawn from this trial. The trial has a major design flaw by comparing the effects of two different lipid-lowering drugs with placebo. Although the SHARP trial showed that lipid lowering may be beneficial for patients with chronic kidney disease, the clinically as well as economically important question remains unanswered as to whether it was statin therapy and/or ezetimibe that mediated this effect. A great opportunity to investigate superiority, equipoise, or potential inferiority of ezetimibe compared to statins was missed.