INEGY better than Crestor™ in Achieving Multiple "Goals" for LDL-Cholesterol & Other CHD Risk Factors in Hypercholesterolemia Patients

Main Category: Cholesterol
Also Included In: Statins;  Cardiovascular / Cardiology
Article Date: 13 Jun 2007 - 1:00 PDT

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INEGY™ (ezetimibe/simvastatin) allowed significantly more patients with hypercholesterolemia than Crestor™(rosuvastatin) to achieve study specified levels ("Goals") for both Low Density Lipoprotein ("bad") cholesterol (LDL-C) and each one of the following coronary heart disease (CHD) risk factors: C-reactive protein (CRP), Apolipoprotein B (Apo B) or Non-HDL-cholesterol (non-HDL-C). This data was presented at the European Atherosclerosis Society (EAS 2007) meeting in Helsinki, Finland.1 The same study also showed that significantly more patients treated with INEGY attained the specified NECP ATP III** target of LDL-C <70mg/dL for high risk patients compared to rosuvastatin.1

Certain lipoproteins/apolipoproteins are associated with atherosclerosis and therefore may be good predictors of cardiovascular disease (CVD) risk in clinical practice, when measured individually, or in ratios. Commenting on the study findings, Professor Alberico Catapano, Professor of Pharmacology, University of Milan, Italy said

**NCEP ATP III is the U.S. National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults, a set of guidelines for effective patient identification, assessment, diagnosis, and treatment.

"Patients with high LDL-C and other risk factors are at increased risk of developing coronary heart disease, which is a rapidly growing epidemic. It is a clinician's priority to provide their patients with optimal treatment benefits. These findings clearly show that patients not only achieve their LDL-C goal but also reduce their levels of other serious risk factors when inhibiting cholesterol absorption and production with ezetimibe / simvastatin, compared to rosuvastatin."

More hypercholesterolemic patients achieved "Goals" for cholesterol and other CHD risk factors with INEGY than rosuvastatin

The double-blind, six-week, parallel group, multicenter post-hoc analysis was carried out in 2,959 hypercholesterolemic patients who were randomized to one of six arms: INEGY (ezetimibe/simvastatin) 10/20 mg, 10/40 mg, 10/80 mg, or rosuvastatin 10 mg, 20 mg, or 40 mg. The primary endpoint was LDL-C reduction from baseline averaged across all doses, and the secondary endpoints included reductions in hs-CRP, Apo B and non-HDL-C.1

Results showed that significantly more patients achieved dual "Goals" for LDL-C (<70mg/dL) and CRP (<2.0 mg/L) with INEGY compared to rosuvastatin at all dose comparisons (rosuvastatin 10 mg = 4.9 percent vs. INEGY 10/20 mg = 16.5 percent; rosuvastatin 20 mg = 15.7 percent vs. INEGY 10/40 mg = 27.0 percent; rosuvastatin 40 mg = 31.3 percent vs. INEGY 10/80 mg = 43.8 percent) (p<0.001).1 The study also demonstrated that more patients receiving INEGY reached goals for Apo B (<90 mg/dL) and LDL-C (<70 mg/dL) at all dose comparisons compared to rosuvastatin (rosuvastatin 10 mg = 8.0 percent vs. INEGY 10/20 mg = 22.9 percent; rosuvastatin 20 mg = 27.4 percent vs. INEGY 10/40 mg = 37.7 percent; rosuvastatin 40 mg = 47.2 percent vs. INEGY 10/80 mg = 63.1 percent) (p<0.001).1

Significantly more patients with triglyceride levels ≥200 mg/dL also achieved Non-HDL-C (<100 mg/dL) and LDL-C (<70 mg/dL)"Goals" with INEGY compared to rosuvastatin at two of the three dose comparisons (rosuvastatin 10 mg = 4.5 percent vs. INEGY 10/20 mg = 14.5 percent; rosuvastatin 40 mg = 42.6 percent vs. INEGY 10/80 mg = 54.6 percent) (p≤0.01). INEGY and rosuvastatin were well tolerated at all doses in the study.1

These results indicate that the greater efficacy of INEGY compared to rosuvastatin generally extends to modifications of some other or emerging risk factors for CHD.

A greater proportion of patients achieved the "Goal" of LDL-C <70 mg/dL with INEGY compared to rosuvastatin

The same study also demonstrated that significantly more patients achieved the single LDL-C "Goal" of <70mg/dL when treated with INEGY compared to rosuvastatin at all dose comparisons (rosuvastatin 10 mg = 9.3 percent vs. INEGY 10/20 mg = 24.2 percent; rosuvastatin 20 mg = 29.7 percent vs. INEGY 10/40 mg = 40.7 percent; rosuvastatin 40 mg = 49.5 percent vs. INEGY 10/80 mg = 65.8 percent) (p<0.001). No differences in safety and tolerability were observed between dose comparisons1.

Defining "inhibition of cholesterol absorption and production" Cholesterol in the body originates from two main sources: absorption in the intestine of both biliary and dietary cholesterol, and production in the liver and peripheral tissues.3,4 Approximately two-thirds of intestinal cholesterol comes from biliary sources; only one third comes from dietary sources.3 Approximately 50 percent of cholesterol in the intestine is absorbed and re-circulated in the blood; the remainder is excreted.4

Cholesterol-lowering agents (statins) reduce cholesterol levels by inhibiting the production (synthesis) of cholesterol in the liver. INEGY™ contains the statin simvastatin, plus the active ingredient of EZETROL™ (ezetimibe), the first and only cholesterol absorption inhibitor which works by inhibiting intestinal absorption of cholesterol.

About INEGY™

INEGY™ has been developed and is being marketed by Merck & Co., Inc., Whitehouse Station, N.J., U.S.A. (NYSE: MRK) and Schering-Plough Corporation (NYSE: SGP) in connection with a partnership formed by both companies to develop and market worldwide (excluding Japan) new prescription medicines in cholesterol management. Branded as INEGY™ in Europe, Middle East and Africa, the product is indicated (in the EU) as adjunctive therapy to diet for use in patients with primary (heterozygous familial and non-familial) hypercholesterolemia or mixed hyperlipidemia where use of a combination product is appropriate: 1) patients not appropriately controlled with a statin alone; and 2) patients already treated with a statin and ezetimibe. INEGY™ has an additional indication for homozygous familial hypercholesterolemia. It has been approved in more than 60 countries around the world including the United States, where the Food and Drug Administration approved it in 2004 - under the brand name VYTORIN - for the treatment of high LDL-C as adjuvant therapy to diet. The tolerability profile of INEGY™ is similar to simvastatin and atorvastatin, and is maintained over long-term therapy.

About Merck

Merck & Co., Inc., Whitehouse Station, N.J., U.S.A., which operates in many countries as MSD (Merck Sharp & Dohme), is a global research-driven pharmaceutical company dedicated to putting patients first. Established in 1891, Merck currently discovers, develops, manufactures and markets vaccines and medicines to address unmet medical needs. The Company devotes extensive efforts to increase access to medicines through far-reaching programs that not only donate Merck medicines but help deliver them to the people who need them. Merck also publishes unbiased health information as a not-for-profit service. For more information, visit http://www.merck.com.

About Schering-Plough

Schering-Plough is a global science-based health care company with leading prescription, consumer and animal health products. Through internal research and collaborations with partners, Schering-Plough discovers, develops, manufactures and markets advanced drug therapies to meet important medical needs. Schering-Plough's vision is to earn the trust of the physicians, patients and customers served by its more than 33,500 people around the world. The company is based in Kenilworth, N.J., and its Web site is http://www.schering-plough.com.

References

1. Ballantyne C et al. Effects of Ezetimibe/Simvastatin vs. Rosuvastatin on Lowering of LDL-Cholesterol as well as Apo-lipoprotein B, Non-HDL-Cholesterol, or C-Reactive Protein - presentation at European Atherosclerosis Society 2007, Helsinki, Finland.
2. A. L Catapano et al. Attainment of Optimal NCEP ATP III Treatment goals in High-Risk Patients: Dose Comparison of Ezetimibe/Simvastatin and Rosuvastatin - presentation at International Symposium of Atherosclerosis 2006, Rome, Italy.
3. Wilson MD, Rudel LL. Review of cholesterol absorption with emphasis on dietary and biliary cholesterol. J Lipid Res 1994; 35:943-955.
4. Clearfield MD. A novel therapeutic approach to dyslipidemia. J Am Osteopath Assoc 2003; 102 (suppl-1): S16-S20