INEGYT Is Superior To Simvastatin In Reducing Key Risk Markers Of Atherosclerosis - Confirmed

Main Category: Cardiovascular / Cardiology
Also Included In: Cholesterol;  Statins
Article Date: 11 Sep 2006 - 16:00 PST

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Results from new analyses of two clinical studies presented today at the 2006 World Cardiology Congress show that INEGY™ (ezetimibe/simvastatin) is effective for reducing apolipoprotein-B containing lipoproteins (apo-B) and C-reactive protein (CRP), both recognized risk markers for atherosclerosis.[1],[2] The studies found that INEGY, which treats two sources of cholesterol -- both cholesterol absorption and production, has a more positive effect than simvastatin alone on both apo-B and CRP levels in hypercholesterolemia patients.
Christie Ballantyne, M.D., director of the Center for Cardiovascular Disease Prevention, Methodist DeBakey Heart Center, Houston, Texas, U.S.A., and lead investigator of one of the clinical studies noted: "In clinical practice, both CRP, which measures inflammation, and apo-B, which measures the total number of atherogenic particles, are predictors of cardiovascular risk. Previous research has demonstrated that INEGY, which is the first single tablet to treat two sources of cholesterol - both production of cholesterol in the liver and absorption of cholesterol in the intestine - is more effective in reducing overall LDL-cholesterol levels than a statin alone. The additional benefit in lowering both CRP and apo-B shown in these two studies points to dual inhibition with INEGY as an important treatment option for hypercholesterolemia patients."

INEGY was more effective than simvastatin alone at reducing lipoprotein subfractions
This analysis compared the effects of ezetimibe alone, simvastatin alone and INEGY (single tablet) on apolipoprotein-B containing lipoprotein subfractions.[1] Lipoproteins are protein compounds that are used to transport lipids around the body in the blood stream and apolipoprotein is the protein component of lipoprotein. Apo-B is particularly significant as it is the major apolipoprotein found in low density lipoprotein cholesterol (LDL-C) or 'bad' cholesterol. In this study, the primary analysis of which was median percent change in subfraction cholesterol for INEGY versus ezetimibe alone and simvastatin alone, 1528 patients with hypercholesterolemia were randomized to receive either INEGY (various dosing combinations) or simvastatin (various mg doses). Cholesterol associated with lipoprotein subclasses was quantified by the vertical autoprofile II method. Results found that INEGY produced significant reductions in very-low-density lipoprotein cholesterol (VLDL-C), intermediate-density lipoprotein cholesterol (IDL-C) and LDL-C versus ezetimibe alone or simvastatin alone.

This trial supports previous research into the relationship between apo-B and apoprotein A-1 (or Apo A-1, the principle apolipoprotein found in high density lipoprotein or 'good' cholesterol) and heart disease. Results from the INTERHEART trial, involving more than 29,000 people, show that the two most important predictors of heart attack risk are cigarette smoking and an abnormal ratio of apo-B to apo A-1, which together predicted two thirds of the global risk of heart attack.[3]

INEGY provided additional incremental CRP and LDL-C lowering beyond that achieved with simvastatin alone.
This post hoc analysis pooled data from three similar randomized, placebo controlled, double blind studies and was conducted to evaluate the CRP lowering effects of ezetimibe, simvastatin and INEGY.[2]

The efficacy of ezetimibe and INEGY was monitored in terms of percent changes from baseline in CRP and LDL-C levels and the percentage of patients achieving defined single and dual LDL-C (<70 and <100 mg/dl) and CRP (<1 and <2g/L) levels, across individual and pooled treatment groups. The treatment groups comprised of 3083 hypercholesterolemic patients who were randomized equally to placebo, ezetimibe 10mg, INEGY (various dosing combinations) or simvastatin (various mg doses).

Pooled INEGY provided additional incremental CRP and LDL-C lowering beyond that achieved with simvastatin alone.
For CRP levels, there was a mean percent reduction from baseline of 14.3 percent for pooled simvastatin, compared to 31 percent for INEGY. In terms of LDL-C, a reduction from baseline of 38 percent for simvastatin and 52.5 percent for INEGY was recorded. Assessing combined LDL-C and CRP level attainment, 47.7 percent of patients taking INEGY achieved LDL-C <100 mg/dl and CRP <2 mg/L, compared to 22.2 percent of patients taking simvastatin. Similarly, 21.6 percent of patients taking INEGY achieved LDL-C <70 mg/dl and CRP <2 mg/L compared to 3.2 percent of patients taking simvastatin. These data represent the percent of patients achieving these levels out of the patients above these levels at baseline.

Treating two sources of cholesterol through Dual Inhibition
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.[4], [5] Approximately two-thirds of intestinal cholesterol comes from biliary sources; one third comes from dietary sources.[6] Approximately 50 percent of cholesterol in the intestine is absorbed and re-circulated in the blood; the remainder is excreted.[7], [8] Cholesterol-lowering agents (statins) reduce cholesterol levels through the partial inhibition of one pathway; that is, 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. INEGY is the first single product to powerfully target two sources of cholesterol through Dual Inhibition of cholesterol production and absorption, providing greater LDL-C reduction and allowing more hypercholesterolemia patients to reach NCEP ATP III* targets.[9], [10]

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About INEGY
INEGY (ezetimibe/simvastatin) has been developed and is being marketed by Merck & Co., Inc. (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. It has been approved in more than 50 nations around the world including the United States, where the Food and Drug Administration approved it on July 23, 2004 - under the brand name VYTORIN - for the treatment of high LDL cholesterol as adjuvant therapy to diet. The tolerability profile of INEGY is similar to simvastatin or atorvastatin and is maintained over long-term therapy.

About Merck
Merck & Co., Inc. is a global research-driven pharmaceutical company dedicated to putting patients first. Established in 1891, Merck discovers, develops, manufactures and markets vaccines and medicines in over 20 therapeutic categories. The company also 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 Corporation 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 30,000 people around the world. The company is based in Kenilworth, N.J., and its web site is http://www.schering-plough.com.

*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.

References

[1] Orse, L. et al. Effects Of Ezetimibe/simvastatin On Lipoprotein Subclasses In Patients With Primary Hypercholesterolemia. 2006 World Cardiology Congress - poster presentation

[2] Ballantyne, CM. et al. Effects of Ezetimibe/Simvastatin Compared to Simvastatin Monotherapy in Reducing C-Reactive Protein and Low Density Lipoprotein-Cholesterol. 2006 World Cardiology Congress - poster presentation

[3] Salim Yusuf, Steven Hawkin et al, Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): Case controlled study. The Lancet. 2004; 364: 937-52

[4] Shepherd J. The role of the exogenous pathway in hypercholesterolemia. Eur Heart J. Suppl 2001;3(suppl E):E2-E5.

[5] Van Heek M, Farley C, Compton DS et al. Comparison of the activity and disposition of the novel cholesterol absorption inhibitor, SCH58235, and its glucuronide, SCH60663. Br J Pharmacol. 2000;129:1748-1754

[6] Wilson MD, Rudel LL. Review of cholesterol absorption with emphasis on dietary and biliary cholesterol. J Lipid Res. 1994; 35:943-955

[7] Clearfield MB. A novel therapeutic approach to dyslipidemia. J Am Osteopath Assoc. 2003;103(suppl 1):S16-S20.

[8] Bays H. Ezetimibe. Expert Opin Investig Drugs. 2002;11(11):15 87-1604

[9] A. L Catapano et al. Lipid-Altering Efficacy and Safety of Ezetimibe/Simvastatin Versus Rosuvastatin in Patients with Primary Hypercholesterolemia - presentation at International Symposium of Atherosclerosis 2006, Rome, Italy

[10] 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

For further information please contact:
Abby Webster
Healthcare & Wellbeing
Hill & Knowlton (UK) Ltd
http://www.hillandknowlton.com

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