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Lowering LDL cholesterol reduces the risk of major atherosclerotic events in patients with chronic kidney disease (CKD), according to researchers in the Study of Heart and Renal Protection (SHARP). “Even though much of the mortality and morbidity attributable to cardiovascular disease in CKD is caused by nonatherosclerotic pathologies, that component of the disease that is attributable to atherosclerosis is preventable using ... LDL-lowering therapy,” summarizes Professor Colin Baigent, lead author of the trial report published in the Lancet.

Patients with CKD (defined as serum or plasma creatinine of at least 150 μmol/l in men or 130 μmol/l in women, whether receiving dialysis or not) were randomly allocated to receive LDL-lowering drugs or a matching placebo. In the active-drug group, 4,650 patients received a combination of a low dose of a statin (20 mg of simvastatin daily) plus a cholesterol-absorption inhibitor (10 mg of ezetimibe daily), a drug regimen that had been shown to be biochemically efficacious in two earlier pilot studies. LDL cholesterol was reduced by an average of 0.85 mmol/l over the median follow-up of 4.9 years, compared with the 4,620 patients in the placebo group. The incidence of major atherosclerotic events (nonfatal myocardial infarction or death from coronary heart disease, nonhemorrhagic stroke, or any arterial revascularization) was significantly lower in patients on simvastatin plus ezetimibe compared with the placebo group (11.3% versus 13.4%, rate ratio 0.83, 95% CI 0.74–0.94, P = 0.002). There was no evidence that simvastatin plus ezetimibe increased the risk of cancer, myopathy, hepatobiliary disorders, or nonvascular causes of death.

The data from this trial indicate that major atherosclerotic events in patients with CKD are reduced by 19% for every 1 mmol/l that LDL cholesterol is lowered. “We now plan to design and conduct future trials of treatments that might reduce the risk of nonatherosclerotic cardiovascular disease in [patients with] CKD,” says Professor Baigent.