Blog entry by Arif Khwaja
Patients with Chronic Kidney Disease (CKD) are at much higher risk of cardiovascular disease than the general population but the benefits of lipid reduction in this population have been far from clear. Recent data from the Study of Heart and Renal Protection (SHARP) study presented at the ASN 2010 may clarify the role of lipid-lowering therapy in this population. SHARP enrolled 9438 patients with chronic kidney disease either on dialysis or with a creatinine level of >1.7 mg/dL (150μmol/l) for men or >1.5 mg/dL (130μmol/l) for women, all with no history of MI or coronary revascularization. Patients were randomised to either ezetimibe/simvastatin (10 mg/20 mg) or placebo, with an additional 1000 patients randomised to simvastatin alone. After one year, patients in the simvastatin-alone arm were re-randomised.
After a median follow-up of nearly 5 years the simvastatin/ezetimibe group had 17% reduction in major atherosclerotic events compared with placebo (p=0.0022) and a 15.3% reduction (p=0.0012) in major vascular events. Approximately 1/3 of patients were on dialysis though the benefit in the dialysis population was not statistically significant. Further simvastatin/ezetimibe had no impact on the progression of CKD nor was there any difference in mortality between the two groups.
So where does this leave us in terms of daily clinical practice? It now seems sensible to use lipid-lowering therapy as a primary preventative measure in CKD patients at risk of vascular events but it is worth noting that even in this huge trial no effect on overall mortality was seen and the reduction in vascular events was quite modest. The simvastatin/ezetimibe combination is clearly safe (concerns about myositis and cancer were not borne out by the data) but it may be that alternative therapies such as atorvastatin could be a cheaper alternative. Whether prevalent dialysis patients should be treated in the same way isn’t so clear. Both the 4D and AURORA studies have failed to show any benefit of statins in the prevalent dialysis population. Clearly clinicians will be able to make more informed decisions once the data is finally published.
The SHARP study data can be seen at: http://www.ctsu.ox.ac.uk/~sharp/slides.htm