For my money, Matt has (by a wide margin), done the best job of condensing what all the news of the week from the FDA means to Merck — do go read all of his — but here is the concluding bit:
. . . .Alan Jardine, a cardiologist at the University of Glasgow, writes that the use of Zetia, by itself or in Vytorin, is “not universally approved,funded, or endorsed,” and that physicians could feel pretty safe about using Crestor or Lipitor instead because their cholesterol-lowering potency is similar. I emailed him, asking whether Vytorin’s success in kidney disease, where other drugs have failed, was the result of the decision to design the study to include fewer sick patient or special characteristics of the drug. He said that the use of Vytorin was probably a “pragmatic decision” based on the fact that Merck designed the study.
I think a statin alone would have the same benefit, and I think most clinicians will use a statin alone. I agree with your interpretation that the benefits are based on the smart design, weighting towards patients with milder kidney disease and the selection of a potentially modifiable end-point. In the UK, 10-15% of the population are classed as having CKD, and that is probably the population they should have studied. The inclusion of patients with more advanced disease was the choice of the investigators – in an attempt to answer the question of the role of statins in dialysis. . . .
The overall trend is that, instead of using Vytorin, doctors are likely to continue starting patients who need intensive cholesterol-lowering on Crestor or Lipitor, and then adding Zetia. The role of the combination could continue to decline. . . .
Indeed. Herper goes on to suggest that Merck’s Zetia® may be added to the Crestor® (AstraZeneca) or Lipitor® (Pfizer) mixes, by some doctors for some patients. I agree, but not enough, in any case, to reverse the trendlines he’s set out, above.
Finally, regular readers will remember — of course — that it was legacy Schering-Plough that actually handled these study design strategies Matt mentions.
Thanks again, Fred and Carrie!