My take: SHARP was powered, and designed, to look at patients with kidney disease, and in many cases, these were end stage renal disease patients. So, SHARP’s results cannot reliably be used to infer that a reduction in cardiovascular events rate benefit will appear in the general cholesterol management population, from Vytorin®.
That is what IMPROVE-IT is designed to figure out, in 2014, or so. Meanwhile, Merck will apply to FDA for approval to revise the Vytorin label, to indicate that it may be of benefit to ESRD patients. Not a very big deal, really.
Most independent thinkers will note — with great interest — that many of the ESRD patients in the SHARP study were actually started on statins, before they became renal patients, or SHARP study participants.
Thus, it is equally probable that the CV event reduction effect seen in SHARP is due to long-term statin use (Vytorin is partly a statin), not due to the Zetia® portion of the pill. [That is essentially what Dr. Jim Stein — a University of Wisconsin cardiologist — says below.]
Here is some of skepticism quoted by Matt Herper — writing for Forbes, this evening — on the SHARP results announcement, from the annual nephrology conference, in Denver:
. . . .Not everyone is so sure. “Statins are good for people,” says James Stein of the University of Wisconsin. He notes that another study – the German Diabetes and Dialysis Study (4D) showed significant reduction is stroke and cardiovascular events with the 20-milligram dose of Lipitor, though the trial failed in its main goal. The relative benefit from Lipitor was 18%, about what was seen in SHARP. By this argument, Sharp proves that diabetics benefit from a cholesterol-lowering regiment that includes a statin like Zocor, but not that the Zetia component did anything. . . .
Mildly good news for people with high cholesterol, and kidney disease, just the same.