Landray M et al. (2006) The second United Kingdom Heart and Renal Protection (UK-HARP-II) study: a randomized controlled study of the biochemical safety and efficacy of adding ezetimibe to simvastatin as initial therapy among patients with CKD. Am J Kidney Dis 47: 385–395

The first United Kingdom Heart and Renal Protection study established simvastatin as an effective, well-tolerated cholesterol-lowering treatment for patients with chronic kidney disease (CKD). Now, results of the second United Kingdom Heart and Renal Protection study indicate that LDL cholesterol levels in this population can be further reduced by adding ezetimibe, a cholesterol absorption inhibitor, to the simvastatin regimen.

This pilot study included 203 CKD patients randomized 1:1 to receive 20 mg simvastatin plus 10 mg ezetimibe daily, or simvastatin alone. After 6 months, mean LDL cholesterol levels had decreased [from 3.1 mmol/l (121 mg/dl) to 1.9 mmol/l (72 mg/dl)] in patients receiving combination therapy—a 21% greater reduction than that seen in patients receiving simvastatin monotherapy (P <0.0001). The addition of ezetimibe to simvastatin was well tolerated, biochemically safe, and was not associated with serious adverse events. Diarrhea was more common, however, in the combination treatment group (27%) than in the control group (12%; P = 0.009).

Whether these LDL cholesterol reductions will translate to improved cardiovascular outcomes in the CKD population is the subject of a larger randomized trial, the Study of Heart and Renal Protection, which is currently underway. Findings from observational studies of CKD patients, however, do not bode well. A large proportion of vascular diseases in such patients are secondary to uremic cardiomyopathy, not acute myocardial infarction, and therefore might not be mitigated by cholesterol lowering.