Discussion

As a nephrologist, what is your perspective on SHARP?

George L. Bakris, MD, FASH, FASN, FACP: I believe that the SHARP trial properly examines the endpoints that are valid in the subgroup of patients that were studied. Although the AURORA and 4D trials, which included patients on dialysis, were both powered to investigate cardiovascular events, they included a number of events that patients on dialysis typically do not have (ie, myocardial infarctions, hemorrhagic stroke, etc). The cardiovascular events that people on dialysis die from are not the cardiovascular events that the general population dies from. Arrhythmias, sudden death, and heart failure are high in this subgroup of patients with stage 4 or higher CKD. The SHARP trial provides a picture that statins do have a role in people with advanced kidney disease. They improve cardiovascular outcomes that are relevant to this group of patients. In fact, the trend in patients on dialysis, while not statistically significant, favored the use of statins.

As a cardiologist, how do you feel about the safety of low-dose to moderate-dose simvastatin therapy in combination with ezetimibe in patients with CKD, based on results of the SHARP trial?

Michael H. Davidson, MD, FACC, FACP, FNLA: The SHARP trial was very reassuring. The risk of myopathy/rhabdomyolysis was similar in the treatment group compared to the control group.

Do you feel that, based on results of the SHARP trial, that lipid-lowering therapy should be an integral component of managing a patient with CKD irrespective of baseline lipids?

Bakris: In general, I would say yes. One exception would be a subgroup of patients that are malnourished, especially those on dialysis. These patients suffer from malnutrition related to depression and poor PO intake. Many of these individuals will have LDL levels that are in the 50s. I am not sure that these patients should receive lipid-lowering therapy.

Do you believe CKD should now be considered a CHD risk equivalent?

Davidson: Yes. I believe there is enough evidence now that it certainly is a powerful risk factor. Two criteria are met for how we decide whether to take action on a risk marker. One criterion is that the risk marker is predictive of high risk. The other is that treating that population with LDL-lowering therapy results in a benefit. Based on these criteria, we can consider patients with CKD a population that deserves more aggressive intervention regardless of their baseline LDL cholesterol level. We now are able to use an evidence-based approach to reducing high cardiovascular disease risk in this patient population.

I do not think it can be definitively concluded from the SHARP trial that patients on dialysis would benefit from simvastatin/ezetimibe combination therapy or LDL-lowering therapy. However, I do believe that this study, which included patients that were not on dialysis, identified a group that can be intervened upon before it is too late, in terms of cardiovascular risk reduction.

John J. Russell, MD: I believe it should, especially because there are measures that can be taken to change it. If results of the SHARP trial can show that this risk equivalent can be changed, then it may make sense to make individuals aware of it.

How would you manage a patient that still has high triglycerides and low HDL, considering reduced renal filtration capacity and how various adjuvant therapies impact triglycerides and HDL?

Davidson: I believe that caution must be exercised in using other treatments in combination with ezetimibe/simvastatin treatment, particularly fibrates. I would be hesitant to use a fibrate in patients with impaired renal function. If a fibrate is going to be used in these patients, it should be used at a marked dose reduction. Niacin is another option, but must also be used with caution, especially in patients with poorly controlled diabetes. Moreover, niacin is cleared renally. Prescription omega-3 fatty acids should be considered as an add-on therapy. They work in the liver, and renal clearance is not a concern. The best option would be lifestyle changes, which are often difficult in this population. An effort with lifestyle changes should be made before switching to pharmacotherapy to modify the lipid profiles of these patients.

Russell: I would probably prescribe fish oils in a 2 to 4 gram dose. I think it is important for people to realize that this treatment normalizes the size of the lipid particles so, often with fish oils, a slight increase in LDL levels may be observed, but it is more of a normalization of particle size then changing the LDL levels.

What do you think is the reason for the suboptimal rates of evaluation for albuminuria or possible CKD etiology in primary care after GFR has been found to be reduced at the stage 2 or 3 levels?

Russell: I believe it is an educational issue. Primary care physicians have not been adequately made aware that a difference can be made in patients with stage 3 and stage 4 kidney disease. Education of the population is important as well. There are individuals with diabetes who do not visit the doctor and do not take their cholesterol medicine, and these people must be educated that diabetic nephropathy, diabetic heart disease, and diabetic retinopathy are not inevitable with the diagnosis of diabetes and can be prevented.