Merck's Vytorin Achieves Primary, Secondary Endpoints in IMPROVE-IT Study

Patients taking Merck’s Vytorin (ezetimibe/simvastatin), which combines simvastatin with the non-statin Zetia (ezetimibe), experienced fewer major cardiovascular events than patients treated with simvastatin alone, according to the results of the IMPROVE-IT study presented at the American Heart Association 2014 Scientific Sessions. The study followed patients for up to 9 years.

The 18,144-patient study of high-risk patients presenting with acute coronary syndromes met its primary and all secondary composite efficacy endpoints. IMPROVE-IT was designed to address whether lowering LDL-cholesterol (LDL-C) to under 70 mg/dL by adding ezetimibe to a statin would reduce cardiovascular events, which were measured by a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, hospitalization for unstable angina, or coronary revascularization occurring at least 30 days after randomization.

“In IMPROVE-IT, the addition of ezetimibe to a statin resulted in a further reduction in cardiovascular events compared to statin therapy alone, which is the first time this has been directly shown in a study of a non-statin cholesterol-lowering medicine,” said study co-chairs, Eugene Braunwald, MD, professor at Harvard Medical School, and Robert Califf, MD, professor at Duke University. “The IMPROVE-IT data also address an important scientific question about lowering LDL-C to very low levels.”

According to the results of the study, Vytorin reduced the risk of heart issues by 6.4%. While 34.7% of patients taking simvastatin alone experienced a cardiovascular event, 32.7% of those on Vytorin experienced the same.

The study also met its secondary endpoints:

• Vytorin reduced the incidence of the composite endpoint of death due to all causes, major coronary events, and non-fatal stroke (38.7% vs 40.3% of patients taking simvastatin alone).
• Fewer of patients on Vytorin experienced death due to coronary heart disease, non-fatal myocardial infarction, and urgent coronary revascularization occurring at least 30 days after randomization (17.5%) compared with 18.9% of patients on simvastatin only.
• On Vytorin, 34.5% of patients experienced cardiovascular death, non-fatal myocardial infarction, documented unstable angina requiring admission into a hospital, all revascularization occurring at least 30 days after randomization, and non-fatal stroke compared with 36.2% of patients taking only simvastatin.

Merck plans to submit data from the study to the FDA in mid-2015 to support a new indication for reduction of major cardiovascular events for Vytorin and Zetia, both of which are currently indicated for use along with a healthy diet to reduce elevated LDL-C in patients with hyperlipidemia.

“We believe that the IMPROVE-IT study makes an important scientific contribution to the body of evidence relating LDL-cholesterol levels to cardiovascular risk,” said Dr Roger Perlmutter, president, Merck Research Laboratories. “We are grateful to our collaborators at Harvard and Duke who led the study, their fellow investigators, and to the thousands of patients around the world who participated in this study for their efforts.”