Margo A. Denke

A Community-Based, Randomized Trial of Ezetimibe Added to Statin Therapy to Attain NCEP ATP III Goals for LDL Cholesterol in Hypercholesterolemic Patients: The Ezetimibe Add-On to Statin for Effectiveness (EASE) Trial

OBJECTIVEnTo determine the extent of reduction in low-density lipoprotein cholesterol (LDL-C) level and improvement in National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) LDL-C goal attainment when ezetimibe was added to ongoing statin therapy in a diverse population of community-based patients.nnnPATIENTS AND METHODSnIn this multicenter, double-blind, placebo-controlled trial (from January 2003 to August 2003), hypercholesterolemic patients (from 299 US primary care and specialty practices) with LDL-C levels exceeding NCEP ATP III goals were randomized (2:1) to receive ezetimibe (10 mg/d) or placebo in addition to their ongoing statin therapy for 6 weeks.nnnRESULTSnIn a study of 3030 randomized patients, ezetimibe added to statin therapy significantly reduced the LDL-C level by an additional 25.8% in the total population, compared with an additional 2.7% reduction with placebo plus statin (treatment difference, -23.1%; P<.001); the treatment difference ranged from -19.9% to -24.0% (P<.001) in each NCEP ATP III risk category subgroup. Significantly (P<.001) more patients (71.0%) treated with ezetimibe added to statin reached their NCEP ATP III target LDL-C level compared with those treated with placebo plus statin (20.6%). The addition of ezetimibe also resulted in improvement in other lipid parameters and high-sensitivity C-reactive protein levels. These benefits were consistent across sex, race, age, statin brand, and dose subgroups. Ezetimibe plus statin therapy was well tolerated, with a safety profile similar to placebo plus statin.nnnCONCLUSIONnAcross multiple subgroups, ezetimibe added to statin therapy consistently produced significant additional improvements in LDL-C levels and goal attainment, as well as in other lipoproteins, compared with addition of placebo. The addition of ezetimibe to statin therapy should be considered for patients not achieving their NCEP ATP III LDL-C goals while receiving statin therapy alone.

Rationale of the diet-heart statement of the American Heart Association. Report of the Nutrition Committee.

132. Cappuccio FP, MacGregor GA. Does potassium supplementation lower blood pressure? a meta-analysis of published trials. J Hypertens. 1991;9:465-473. 133. Witteman JC, Willett WC, Stampfer MJ, Colditz GA, Sacks FM, Speizer FE, Rosner B, Hennekens CH. A prospective study of nutritional factors and hypertension among US women. Circulation. 1989;80:1320-1327. 134. Joffres MR, Reed DM, Yano K. Relationship of magnesium intake and other dietary factors to blood pressure: the Honolulu heart study. Am J Clin Nutr. 1987;45:469-475. 135. Intersalt Cooperative Research Group. Intersalt: an international study of electrolyte excretion and blood pressure: results for 24-hour urinary sodium and potassium excretion. BrMed J. 1988; 297:319-328. 136. The effects of nonpharmacologic interventions on blood pressure of persons with high normal levels: results of the Trials of Hypertension Prevention, Phase I. JAMA. 1992;267:1213-1220. 137. Schotte DE, Stunkard AL. The effects of weight reduction on blood pressure in 301 obese patients. Arch Intern Med. 1990;150:

Summary of the Scientific Conference on Dietary Fatty Acids and Cardiovascular Health Conference Summary From the Nutrition Committee of the American Heart Association

The objective of this Executive Summary is to provide a synopsis of the research findings presented at the American Heart Association conference “Dietary Fatty Acids and Cardiovascular Health—Dietary Recommendations for Fatty Acids: Is There Ample Evidence?” held on June 5–6, 2000, in Reston, Va. The conference was held to summarize the current understanding of the effects of fatty acids on risk of cardiovascular disease (CVD) and cancer, as well as to identify gaps in our knowledge base that need to be addressed. There is great interest in learning more about the biological effects of the individual fatty acids, their role in chronic disease risk, and their underlying mechanisms of action. As research advances are made, there is always the need to question how new findings may be translated into practice. There is a long history of research providing the basis for the modification of existing dietary guidelines. Research findings have been used to verify intake criteria and are considered along with practical issues of implementation to establish new guidelines. A substantive body of consistent evidence sufficient to defend a dietary recommendation or a change in existing dietary guidance is essential. The conference highlighted the progress that has been made in understanding the biological effects of fatty acids and also addressed the need to learn more about how different fatty acids affect the risk of chronic disease, within the context of refining dietary guidance to further enhance health.nnAs study designs have become increasingly rigorous, a number of megatrends have emerged from the data.1 2 There is increased emphasis on identifying the type of fat that best correlates with disease end points. The classic studies of Keys et al3 and Hegsted et al4 have shown that saturated fatty acids (ie, those with a carbon chain length of C12:0 …

Ezetimibe added to ongoing statin therapy improves LDL-C goal attainment and lipid profile in patients with diabetes or metabolic syndrome

This analysis of the Ezetimibe Add-on to Statin for Effectiveness (EASE) trial examined the effectiveness and safety of ezetimibe 10 mg added to ongoing statin therapy in patients with diabetes, metabolic syndrome without diabetes, or neither disorder who had low-density lipoprotein cholesterol (LDL-C) levels exceeding National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) goals. After six weeks of treatment, ezetimibe added to statin reduced LDL-C in patients with diabetes by 28%, metabolic syndrome by 24%, or neither by 26%, compared with a 3% reduction for placebo for each group. In each group, more patients receiving ezetimibe plus statin reached LDL-C goal (67–74%) compared with those receiving placebo plus statin (19–22%). Other parameters demonstrating greater improvement with ezetimibe included triglycerides, apolipoprotein (Apo)B/Apo A-I ratio, high-density lipoprotein cholesterol (HDL-C), and C-reactive protein. Ezetimibe plus statin was well tolerated in each group. Ezetimibe added to ongoing statin therapy offers a new treatment option that is consistently effective in improvement of lipid profiles and attainment of LDL-C goals in patients with or without diabetes or metabolic syndrome.

Weighing in Before the Fight Low-Density Lipoprotein Cholesterol and Non–High-Density Lipoprotein Cholesterol Versus Apolipoprotein B as the Best Predictor for Coronary Heart Disease and the Best Measure of Therapy

In this issue of Circulation , Pischon and colleagues1 present provocative data pitting the power of non–high-density lipoprotein cholesterol (non-HDL-C) versus apolipoprotein (apo) B to predict coronary heart disease (CHD) development in healthy men. They conclude not only that apoB is a superior predictor of CHD risk but, in addition, that “the practical application of our findings would be the substitution of apoB for LDL-C and non-HDL-C for screening and treatment of CHD risk.”nnArticle p 3375 nnThe article presents a healthy spar—a bob and weave—between apoB and the cholesterol concentrations in apoB-containing lipoproteins. The contenders could be fraternal twins because they are strikingly similar. They may be conjoined, making any competition between parts more akin to self-mutilation. This coveted prize must be earned by more than a simple sparring competition.nnGuidelines for lipid management are not valuable unless the measurement of the indicator variable can be made reliably and reproducibly. The present standards for total cholesterol (TC) and HDL-C are a bias ≤3% and ≤5% (accuracy) with a coefficient of variation (CV) ≤3% and ≤4% (precision) with a total error of ≤8.9% and ≤13%, respectively.2nnBefore the mid-1980s, CVs for apoB averaged 30%. The development of standardized methods and suitable reference standards has led to marked improvements in reliability with an average bias of 2.1% (range −5.0 to 3.8%) and an average CV of 2.6% (range 0.9 to 5.1%).3 These appear to be comparable to that expected for non-HDL-C derived from TC and HDL-C measurements.nn### Round 1 Score: 10:10nnBoth are reliable measurements.nnInterindividual day-to-day variation in apoB is similar to that found for TC (5% to 7%); calculated LDL-C is higher at 9% and non-HDL-C is probably in a similar range.4 Variation from race and gender finds higher mean non-HDL-C in men than in women (160 versus 154 …

Effectiveness of Ezetimibe Added to Ongoing Statin Therapy in Modifying Lipid Profiles and Low-Density Lipoprotein Cholesterol Goal Attainment in Patients of Different Races and Ethnicities: A Substudy of the Ezetimibe Add-On to Statin for Effectiveness Trial

OBJECTIVEnTo examine whether the improvements in lipid profiles and low-density lipoprotein cholesterol (LDL-C) goal attainment found in the Ezetimibe Add-On to Statin for Effectiveness trial occurred equally in the black, Hispanic, and white patient populations enrolled in the study.nnnPATIENTS AND METHODSnIn this double-blind, placebo-controlled study, patients were recruited from 299 community-based practices across the United States (January to August 2003). Patients with, hypercholesterolemia and LDL-C levels exceeding National Cholesterol Education Program Adult Treatment Panel III goals were randomized (2:1) to receive either ezetimibe (10 mg/d) or placebo in addition to their ongoing statin therapy for 6 weeks.nnnRESULTSnA total of 5802 patients were screened at baseline for the Ezetimibe Add-On to Statin for Effectiveness study. Of these, 2772 were excluded, and the remaining 3030 eligible patients were randomized. Ezetimibe, compared with placebo, added to statin therapy significantly reduced LDL-C levels from statin-treated baseline by 23.0% (white patients), 23.0% (black patients), and 21.0% (Hispanic patients). This effect was consistent across race and ethnicity groups (P > .50 for treatment-by-race interactions). Ezetimibe added to statin therapy also statistically significantly (P < .001) increased the percentage of patients attaining their LDL-C goal for their National Cholesterol Education Program Adult Treatment Panel III risk category in black (63.0%), Hispanic (64.8%), and white (72.3%) patients compared with placebo plus statin (32.9% black patients, 19.0% Hispanic patients, and 19.7% white patients). Ezetimibe treatment improved other lipid parameters across groups, including triglyceride, high-density lipoprotein cholesterol, non-high-density ilpoprotein cholesterol, and total cholesterol levels. Finally, the addition of ezetimibe reduced high-sensitivity C-reactive protein levels overall, and no significant interaction of treatment by race occurred (P = .83), Indicating a consistent effect across races. Ezetimibe was generally well tolerated, and no detectable differences occurred in the adverse event profile by race or ethnicity.nnnCONCLUSIONnEzetimibe added to statin therapy is effective and well tolerated for improving the lipid profile and LDL-C goal attainment of patients regardless of race or ethnicity.