November 20th, 2010
SHARP Shows Benefit for Vytorin in Chronic Kidney Disease
The long-awaited SHARP study has turned up positive results for Vytorin (ezetimibe and simvastatin) in a population of patients with chronic kidney disease. Results of SHARP (Study of Heart and Renal Protection) were presented on Saturday at the American Society of Nephrology meeting in Denver and were scheduled to be posted online on the trial’s website.
SHARP compared Vytorin to placebo in 9,438 patients with chronic kidney disease and found that Vytorin-treated patients had a significant (p=0.0010) 16.1% reduction in the incidence of first major vascular event (nonfatal MI or cardiac death, stroke, or revascularization). A first major vascular event occurred in 15.2% of patients in the Vytorin group compared to 17.9% of patients in the placebo group.
It should be noted that the SHARP steering committee sought to change the primary endpoint (from first major vascular event to first major atherosclerotic event) and the planned statistical analysis of the trial to avoid producing a false negative result. The trial sponsor, Merck, did not endorse their plan. However, the SHARP investigators reported a similar 16.5% reduction (p=0.0022) in the proposed new endpoint, which occurred in 13.4% of the placebo group compared to 11.3% in the Vytorin group.
It should also be noted that the primary analysis of major vascular events did not include approximately 1,000 patients who took simvastatin monotherapy for the first year of the trial before being re-randomized to either Vytorin or placebo. When this group is included in the analysis the results remain substantially the same, producing a 15.3% reduction (p=0.0012), with a major vascular event occurring in 17.6% of the placebo group versus in 15.1% of the Vytorin group.
During the first year, when compared to placebo, LDL dropped by 40% in the Vytorin group and 28% in the simvastatin group. At 2.5 years, LDL cholesterol was reduced by 30% in the Vytorin group.
About a third of patients in the trial were undergoing dialysis. Among patients not on dialysis at the start of the study, there was no difference in the progression to end-stage renal disease between Vytorin and placebo.
The investigators reported no unexpected safety issues. Cancer was reported in 9.4 % of patients in the Vytorin group versus 9.5% in the placebo group.