Tag Archives: TheHeart.org HeartWire SHARP Vytorin End Point Redefined Clinical Trial SHARP IMRPOVE-IT 2014 October 6 November 21 2010

Reiterating Dr. James Stein’s Central Point — On SHARP


As I earlier wrote, and Matt Herper has noted, SHARP showed only a very slight outcome benefit from Vytorin®, in renal disease patients.

I want to reiterate, then what James Stein, MD — of the University of Wisconsin’s Cardiology program — told Matt, over the weekend: theoretically speaking, all of the benefit seen in SHARP may be due to the presence of a simple statin, in Vytorin’s combination. So why pay 50 to 100 times the price — when a generic statin may well be the primary active agent?

That will be the question. . . as we wait for IMPROVE-IT. Here, again is Dr. Stein’s pullquote, from the Forbes piece:

. . . .[In other studies,] 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. . . .

Indeed. We will wait until 2014, or beyond, for that answer.

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Matt Herper — A “Sharp,” On SHARP — And Pretty Solidly, Too


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.