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
The ‘long and slow’ approach to haemodialysis as advocated by the group from Tassin, France has yielded impressive results in terms of blood pressure control and patient survival. This has lead to increasing interest in daily haemodialysis as more effective alternative to the standard thrice weekly prescription.
Chertow, Levin and other members of the Frequent Hemodialysis Network (FHN) report the early (12 months ) results of their study involving 245 patients comparing in center haemodialysis (HD) six times per week compared to three times per week. They conclude that frequent HD, as compared to conventional HD, was associated with a favourable outcome. Emphasis was on progression of left ventricular mass, death and quality of life based on a physical-health composite score. Whilst promising, this study is limited by the very short follow-up period that precludes any conclusion on long term outcomes in HD patients dialysed more frequently. Outcomes are also difficult to evaluate as left ventricular mass index may reflect a better fluid balance and reduced blood volume in those dialysed more frequently. Quality of life and evaluation of physical health through health surveys and questionnaires can be biased by the non-blinded nature of the study -patients dialysed six times weekly may be subject to the placebo effect of frequent medical attention.
Interestingly, the daily HD group were much more likely to experience vascular access problems. Furthermore the study was underpowered and the sample size too small to show differences in survival over such a short period of time in such patients population.
Reference: In-Center Hemodialysis Six Times per Week versus Three Times per Week. The FHN Trial Group. N Engl J Med 2010; 363:2287-2300