Dr. Neil J. Stone
“If we had made a leap of faith that lower is better, we wouldn’t have done those trials,” he observed.
Also, it’s important to recognize that the IMPROVE-IT data don’t speak to the use of ezetimibe for primary prevention in lower-risk patients. “This study is not a signal that everyone should be on ezetimibe,” Dr. Stone emphasized.
It’s estimated that, in clinical practice, up to 25% of patients are statin intolerant to varying degrees. Dr. Watson said that, after seeing the IMPROVE-IT results, “I would absolutely try to persist with statin therapy, but there are some patients who are truly statin intolerant, and for them I might add ezetimibe to a low-dose statin.”
Indeed, like many other physicians, she has been doing that all along in selected cases on the basis of clinical judgment and biologic plausibility while anxiously awaiting the IMPROVE-IT findings, which come as a great relief, she added.
IMPROVE-IT was initially planned to include 10,000 randomized patients and a minimum of 2.5 years of on-treatment follow-up. Over the years, however, it underwent four protocol amendments. As IMPROVE-IT kept growing larger and longer, some observers quipped that it appeared the organizers would just keep the trial going until it produced a positive result, although, in fact, the study leaders remained blinded to the interim safety and efficacy data.
Merck, which sponsored the study, announced that it will use the data in petitioning the Food and Drug Administration next year for a new indication for reduction of major cardiovascular events for Vytorin and ezetimibe (Zetia).
Dr. Cannon reported receiving research grants from Merck and half a dozen other pharmaceutical companies. Dr. Watson reported participating in the clinical trials adjudication committee for Merck. Dr. Smith and Dr. Stone had no disclosures.
*Correction, 11/18/14: An earlier version of this article carried an incorrect photo credit.