The FINANCIAL — Merck (NYSE:MRK), known as MSD outside the United States and Canada, on March 16 announced results from a pre-specified exploratory analysis of the investigational IMPROVE-IT study of more than 18,000 patients presenting with acute coronary syndromes.
The new analysis shows that VYTORIN (ezetimibe/simvastatin) – which combines simvastatin with the non-statin ZETIA (ezetimibe) – reduced total (defined as initial and recurrent) cardiovascular events by 9% compared to simvastatin alone (incidence-rate ratio [IRR] 0.91, 95% CI 0.85-0.97, p=0.007; by treatment group, 4,562 vs. 4,983 total events, respectively). These data were presented as part of this afternoon’s late-breaking featured clinical research session at the 2015 American College of Cardiology Scientific Sessions, according to Merck.
The results on the trial’s primary endpoint of initial cardiovascular (CV) events – a composite of first CV death, non-fatal myocardial infarction, non-fatal stroke, re-hospitalization for unstable angina or coronary revascularization occurring at least 30 days after randomization – have been previously reported. For the primary endpoint, VYTORIN provided a 6.4% relative risk reduction compared to simvastatin alone (7-year event rates: 32.7% in the VYTORIN group vs. 34.7% in the simvastatin group; hazard ratio 0.936, p=0.016). The mean LDL-C at one year was 53 mg/dL in the VYTORIN group and 70 mg/dL in the simvastatin group. VYTORIN and ZETIA are indicated for use along with a healthy diet to reduce elevated LDL-C in patients with hyperlipidemia. The U.S. Prescribing Information for both products states that the effect of ezetimibe on CV morbidity and mortality, alone or incremental to statin therapy, has not been determined.
“In this new analysis, VYTORIN (ezetimibe/simvastatin) was shown to reduce the risk of total cardiovascular events, including those beyond the first event – in patients with already low LDL-C,” said Christopher Cannon, MD, professor of medicine at Harvard Medical School in the Cardiovascular Division at Brigham and Women’s Hospital. “The wealth of data from IMPROVE-IT is helping to address important scientific questions about the potential to further reduce cardiovascular risk in patients who have achieved very low LDL-C levels.”
In this analysis, researchers evaluated events comprising the primary endpoint during a median six year follow-up among the trial’s 18,144 participants. The analysis included 9,545 initial and recurrent events. Of these, 56% were first (i.e., primary composite endpoint) events, and 44% were subsequent events observed within that group. Among patients assigned to VYTORIN (ezetimibe/simvastatin), there were 2,572 first events and 1,990 subsequent events; among those assigned to simvastatin, there were 2,742 first events and 2,241 subsequent events. VYTORIN reduced total events by 9% vs. simvastatin alone (incidence-rate ratio [IRR] 0.91, 95% CI 0.85-0.97, p=0.007). This finding is based on the previously-reported 6.4% reduction in first events (HR 0.936 95% CI 0.887-0.988, p=0.016), along with a 12% reduction in recurrent events observed in the present analysis (IRR 0.88, 95% CI 0.79-0.98).
VYTORIN should not be taken with strong CYP3A4 inhibitors (e.g., itraconazole, ketoconazole, posaconazole, voriconazole, HIV protease inhibitors, boceprevir, telaprevir, erythromycin, clarithromycin, telithromycin, nefazodone, and cobicistat-containing products); or with gemfibrozil, cyclosporine, or danazol. VYTORIN also should not be taken by anyone with active liver disease, unexplained persistent elevations of hepatic transaminase levels, or hypersensitivity to the product; or by women who are pregnant, nursing or may become pregnant. ZETIA (ezetimibe) should not be taken by people with hypersensitivity to any component of the medication. Statin contraindications also apply when ZETIA is used with these drugs: statins are contraindicated in patients with active liver disease, unexplained persistent elevations in hepatic transaminase levels and in pregnant and nursing women. Refer to individual statin labels for details about who should not take that statin.
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