An FDA advisory committee has voted in favor of approving ezetimibe/simvastatin (Vytorin – Merck) for prevention of major cardiovascular events in patients with chronic kidney disease who are not on dialysis. The FDA itself is expected to make a decision on this potential new indication in the first quarter of 2012.

The manufacturer’s application for this new indication was based on a double-blind, randomized trial (SHARP) that compared the combination of ezetimibe 10 mg and simvastatin 20 mg with placebo in 9270 patients with chronic kidney disease who did not have a history of myocardial infarction or coronary revascularization.1 About one-third of patients were already on hemodialysis at the start of the trial. Over a median of 4.9 years, a major atherosclerotic event (the primary endpoint) occurred in 526 patients (11.3%) taking the active drugs and in 619 (13.4%) taking placebo. Myopathy occurred in 9 patients (0.2%) randomized to ezetimibe/simvastatin and in 5 (0.1%) of those in the placebo group, not a significant difference.

Whether simvastatin alone, which would cost much less, would similarly improve outcomes in such patients remains to be determined. The FDA advisory committee did not recommend approval of Vytorin for patients who were on hemodialysis.2 Previous trials with a statin alone in patients with end-stage renal disease on hemodialysis failed to show significant benefits in clinical outcomes.3,4

1. C Baigent et al. The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): a randomised placebo-controlled trial. Lancet 2011; 377: 2181.

2. S Sutter. Merck’s bid for Vytorin CV benefit claim muddled by earlier statin failures in dialysis patients. The Pink Sheet, November 7, 2011.

3. C Wanner et al. Atorvastatin in patients with type 2 diabetes mellitus undergoing hemodialysis. N Engl J Med 2005; 353:238.

4. BC Fellström et al. Rosuvastatin and cardiovascular events in patients undergoing hemodialysis.N Engl J Med 2009; 360:1395.

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In the Medical Letter article on Ferumoxytol (Feraheme) - A New Parenteral Iron Formulation (2010; 52:23), the last sentence of the Dosage, Administration and Cost paragraph should have listed the cost of 1 gram of sodium ferric gluconate (Ferrlecit) as about $600.

Ferumoxytol (Fer yoo mox’ i tole; Feraheme – AMAG), an intravenous (IV) iron replacement product, has been approved by the FDA for treatment of iron deficiency anemia in adults with chronic kidney disease. Iron deficiency anemia is common in chronic kidney disease and may be associated with decreased absorption from the gastrointestinal tract, limiting the usefulness of oral iron replacement. IV iron replacement can lower the dose requirement for erythropoiesis-stimulating drugs, particularly in patients on dialysis

The erythropoiesis-stimulating agents (ESAs) epoetin alfa (Epogen, Procrit) and darbepoetin alfa (Aranesp) are widely used for treatment of anemia and to reduce the need for red blood cell transfusions. Based on the results of recent clinical trials indicating an increased risk of serious adverse events and death associated with ESAs, particularly when used to achieve a hemoglobin concentration ≥12 g/dL, the FDA has revised the prescribing information for these drugs to include a black box warning.