While the cardiovascular benefits of LDL cholesterol lowering in patients without kidney disease are well established, the effects on people with moderate to severe kidney disease has remained unproven.
The SHARP (Study of Heart and Renal Protection) study was a randomised double-blind trial that included 9270 patients with chronic kidney disease (3023 of whom were on dialysis) and with no known history of cardiovascular disease. Patients were randomly assigned either to placebo or a combination of simvastatin 20mg od plus ezetimibe 10mg od. The main outcome measure was defined as a first major cardiovascular event (fatal or non-fatal MI, ischaemic stroke, or any arterial revascularisation procedure).
In the study 4650 patients were assigned to receive simvastatin plus ezetimibe and 4620 to placebo; those that received the LDL lowering drugs demonstrated an average LDL cholesterol difference of 0.85 mmol/L over a median follow-up of 4.9 years. This translated into a 17% proportional reduction in major atherosclerotic events (526 [11·3%] simvastatin plus ezetimibe vs 619 [13·4%] placebo; rate ratio [RR] 0·83, 95% CI 0·74–0·94; log-rank p=0·0021). Although non-significantly fewer patients allocated to simvastatin plus ezetimibe had a non-fatal myocardial infarction or died from coronary heart disease (213 [4·6%] vs 230 [5·0%]; RR 0·92, 95% CI 0·76–1·11; p=0·37), there were significant reductions in non-haemorrhagic stroke (131 [2·8%] vs 174 [3·8%]; RR 0·75, 95% CI 0·60–0·94; p=0·01) and arterial revascularisation procedures (284 [6·1%] vs 352 [7·6%]; RR 0·79, 95% CI 0·68–0·93; p=0·0036). After weighting for subgroup-specific reductions in LDL cholesterol, there was no good evidence that the proportional effects on major atherosclerotic events differed from the summary rate ratio in any subgroup examined, and, in particular, they were similar in patients on dialysis and those who were not.
In the SHARP trial, reduction of LDL cholesterol with a combination of simvastatin 20mg od and ezetimibe 10mg od was safe and reduced the incidence of major atherosclerotic events in a wide range of patients with chronic kidney disease.
- Baigent C, Landray MJ, Reith C et al. The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): a randomised placebo-controlled trial. Lancet 2011; 377: 2181–92