The FINANCIAL — Merck, known as MSD in the United States and Canada, on September 1 announced results from new analyses from the IMPROVE-IT study.
“IMPROVE-IT presents us with the opportunity to look at cardiovascular outcomes data for patients treated with the combination of simvastatin and ezetimibe (VYTORIN) and allows us to look at the important aspect of long-term safety and efficacy under controlled conditions,” said Dr. Michael A. Blazing, Duke Department of Medicine.
VYTORIN (ezetimibe and simvastatin) and ZETIA (ezetimibe) 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. Merck has submitted the data from the IMPROVE-IT study to the U.S. Food and Drug Administration to support a new indication for reduction of cardiovascular events for ZETIA and VYTORIN, according to Merck.
Incidence of New Onset Diabetes in the IMPROVE-IT Trial: Does Adding Ezetimibe to Simvastatin Increase Risk Compared to Simvastatin Alone?
The results of one of the analyses presented at ESC showed that patients treated with VYTORIN – which combines simvastatin with the non-statin ZETIA – showed a similar risk of new onset diabetes mellitus (DM) compared to simvastatin alone over a period of >5.5 years median follow-up. During the trial, 1,414 patients (13.3% of those without diabetes at enrollment) developed new onset DM defined as initiation of a diabetes medication or two consecutive fasting glucose levels ≥7 mmol/L (126 mg/dL). Of the new onset DM cases, 50.9% occurred in the VYTORIN (ezetimibe and simvastatin) arm and 49.1% in the simvastatin arm (hazard ratio 1.04; 95% CI 0.94-1.15).
Safety and Efficacy of Long-term Very Low Achieved LDL-C in the IMPROVE-IT Trial
This post-hoc analysis compared safety and efficacy data during the median six years follow-up in patients stratified by achieved LDL-C at month one of the trial. This analysis assessed patients achieving LDL-C levels <30 mg/dL, 30 – <50 mg/dL, 50 – <70 mg/dL and ≥70 mg/dL at month one of the trial. The nine selected safety events of special interest, which included hemorrhagic stroke and adverse events leading to treatment discontinuation, showed similar rates in patients with LDL-C <30 mg/dL at month one (achieved by 6% of patients) compared with patients with higher achieved LDL-C levels. For a complete list of all the safety parameters analyzed please visit the ESC website. In addition, this analysis concluded that cardiovascular events occurred less frequently in patients who achieved an LDL-C level <70 mg/dL at month 1 of the trial compared with LDL-C levels ≥70 mg/dL.
Achievement of Dual LDL-C (<70 mg/dL) and hs-CRP (<2 mg/L) Goals More Frequent with Addition of Ezetimibe and Associated with Better Outcomes in IMPROVE-IT
Additional evidence relating to the efficacy of VYTORIN comes from another IMPROVE-IT analysis, which assessed outcomes in subjects achieving specific levels of LDL-C and high sensitivity C-reactive protein (hs-CRP). CRP levels, a marker of inflammation, are associated with a higher cardiovascular risk in some settings. This analysis showed that patients achieving both LDL-C <70 mg/dL and hs-CRP <2 mg/L at one month had a lower rate of the primary composite endpoint of major CV events over the course of the trial compared with patients not achieving either level. Significantly more patients treated with VYTORIN met these specified dual levels at month one compared to patients treated with simvastatin alone (50% vs 29%, p<0.001).