Merck, known as MSD outside the United States and Canada, has announced that the investigational IMPROVE-IT study met its primary and all secondary composite efficacy endpoints. In IMPROVE-IT, patients taking the LDL-cholesterol-lowering medicine VYTORIN® (ezetimibe/simvastatin) – which combines simvastatin with the non-statin ZETIA® (ezetimibe) – experienced significantly fewer major cardiovascular events (as measured by a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, re-hospitalization for unstable angina or coronary revascularization occurring at least 30 days after randomization) than patients treated with simvastatin alone. The results from this 18,144-patient study of high-risk patients presenting with acute coronary syndromes were presented during the late-breaking clinical trials session at the American Heart Association 2014 Scientific Sessions.
Because high-risk patients treated with statins, including those on treatment with low levels of LDL-cholesterol (LDL-C), continue to be at increased cardiovascular risk, IMPROVE-IT was designed to address whether lowering LDL-C to well under 70 mg/dL by adding ezetimibe to a statin further reduced cardiovascular events. In IMPROVE-IT, at seven years, 32.7 percent of patients taking VYTORIN experienced a primary endpoint event compared to 34.7 percent of patients taking simvastatin alone (hazard ratio of 0.936, p=0.016). Based on the LDL-C range compared in the study’s treatment arms (at one year, a mean LDL-C of 53 mg/dL versus 70 mg/dL, respectively), the 6.4 percent relative risk reduction observed in the VYTORIN arm in IMPROVE-IT was consistent with the treatment effect that had been projected based on prior studies of statins.
Merck plans to submit the data from IMPROVE-IT to the U.S. Food and Drug Administration in mid-2015 to support a new indication for reduction of major cardiovascular events for VYTORIN and ZETIA. VYTORIN and ZETIA are currently indicated for use along with a healthy diet to reduce elevated LDL cholesterol in patients with hyperlipidemia. The current U.S. Prescribing Information for both products states that the effect of ezetimibe on cardiovascular morbidity and mortality, alone or incremental to statin therapy, has not been determined.
“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, Drs. Eugene Braunwald of Harvard Medical School and Robert Califf of Duke University. “The IMPROVE-IT data also address an important scientific question about lowering LDL-C to very low levels.”