Ezetimibe/simvastatin cuts cardiovascular events in CKD

Treatment with ezetimibe plus simvastatin (Inegy) significantly reduced major atherosclerotic events in patients with chronic kidney disease (CKD), whether or not they were on dialysis, the SHARP study has shown (Lancet 2011;377;2181–92).

    The Study of Heart And Renal Protection randomised 9720 patients with CKD (one-third on dialysis) to treatment with ezetimibe 10mg plus simvastatin 20mg or placebo. Ezetimibe was used to achieve an adequate reduction in lipid levels without high-dose statin therapy to reduce the risk of myopathy. At baseline, mean nonfasting total cholesterol was 4.9mmol per litre and mean LDL-cholesterol was 2.8mmol per litre.
    After a median follow up of 4.9 years, the mean reduction in LDL-cholesterol was 0.60mmol per litre in patients on dialysis and 0.96mmol per litre in others; this difference was due to a lower baseline level and worse compliance (54 vs 65%).
    The incidence of major atherosclerotic events was 11.3% with ezetimibe/simvastatin and 13.4% with placebo (rate ratio 0.83, CI95% 0.74–0.94). Lipid-lowering therapy also significantly reduced the incidence of nonhaemorrhagic stroke (2.8 vs 3.8% with placebo) and revascularisation procedures (6.1 vs 7.6%) but not nonfatal myocardial infarction or death from coronary heat disease (4.6 vs 5%). There was no difference in the incidence of all-cause death (24.6 vs 24.1%) and progression of renal disease was unchanged.
    The frequency of myopathy was 0.2% with ezetimibe/simvastatin and 0.1% with placebo; there was no excess risk of gallstones, hepatitis or cancer.