The nitty-gritty on Merck & Co.'s ($MRK) Zetia outcomes trial is now revealed--and it's not just good news for the cholesterol-fighting drug and its combo-pill sister Vytorin. It's good for all high-powered cholesterol meds.
Just as the conference presentation suggested back in November, adding Zetia (ezetimibe) to Merck's statin med simvastatin cut heart risks by 6.4% in patients with acute coronary syndrome, the New England Journal of Medicine study showed. That is, 32.7% of patients in that arm of the study suffered one of the complications that made up the study's primary endpoint, compared with 34.7% of those taking simvastatin alone.
That's not because Zetia has some unique benefit that other cholesterol-lowering agents don't, the medical journal points out in a companion editorial. The IMPROVE-IT study results are simply more evidence that lowering LDL cholesterol prevents cardiovascular problems.
"[T]he real implication of IMPROVE-IT is to suggest that all reductions in LDL levels, regardless of mechanism, are of equivalent benefit," write Drs. John Jarcho and John Keany of the University of Massachusetts Medical School in the editorial.
As Medscape points out, IMPROVE-IT participants taking ezetimibe plus simvastatin--the combination Merck sells as Vytorin--achieved LDL reductions to 53.7 mg/dL (on average) from 93.8 mg/dL. Those taking only simvastatin reduced their LDL levels to 69.5 mg/dL from 93.8 mg/dL. Given those differences, the reduction in cardiovascular events was just about the size number-crunchers would expect based on data from other cholesterol-drug trials, the editorial writers contend.
The study may show that Zetia carries no special benefit in itself beyond its ability to lower cholesterol--but it also shows that statins' benefits are all about LDL-lowering, too, IMPROVE-IT author Robert Giuliano, of Brigham & Women's Hospital, told Heartwire.
So, it's all about that LDL number--be it high-dose statin therapy, lower-dose statin therapy plus Zetia--or, down the road, lower-dose statin therapy plus a PCSK9 drug such as Amgen's ($AMGN) forthcoming Repatha, or Sanofi ($SNY) and Regeneron's ($REGN) Praluent.
Repatha and Praluent will have their outcomes results, too; the studies are underway now. But IMPROVE-IT has already done them a favor by showing that an add-on, non-statin drug can cut cardiovascular risks by delivering bigger LDL reductions.
In the meantime, the IMPROVE-IT results are likely to make doctors more willing to experiment with Zetia as an add-on to statins, or for patients who can't tolerate that class of meds, ISI Group analyst Mark Schoenebaum said when the IMPROVE-IT results were first announced. Merck isn't likely to get a big sales boost, though, Schoenebaum figures, and certainly not a long-term one; Zetia goes off patent in 2017.
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