American College of Cardiology: Ezetimibe Plus Simvastatin for Hypercholesterolemia

Speaker: Christie Ballantyne, MD, Director of the Center for Cardiovascular Disease Prevention, and Professor of Medicine, Baylor College of Medicine and The Methodist De Bakey Heart Center, Houston, Texas.

In patients with high cholesterol levels (EZE) plus simvastatin  (both manufactured by Merck/Schering Plough), were given. These two agents, which inhibit both cholesterol synthesis and intestinal absorption, provided significantly greater reductions in LDL-C for a range of doses, compared with atorvastatin monotherapy in all dosing ranges.

A total of 788 patients underwent a four-week diet/placebo run-in period. They were then randomly assigned to three treatment groups. Each group underwent four sequential, six-week treatment periods:

  • in period 1, titrated to 20, 40, and 80 mg in periods 2 to 4
  • EZE 10 mg with simvastatin 10 mg in period 1, titrated to EZE 10 mg with simvastatin 20 mg, to EZE 10 mg with simvastatin 40 mg, and to EZE 10 mg with simvastatin 80 mg from periods 2 to 4
  • EZE 10 mg with period 1, titrated to EZE 10 mg with simvastatin 40 mg for periods 2 and 3
  • EZE 10 mg with simvastatin 80 mg in period 4

The primary endpoint of this study was the mean percent change in LDL-C from the baseline to the end of period 1 with key secondary endpoints, including mean percent change in LDL-C from the baseline to the end of periods 2, 3, and 4 and the percent change in high-density lipoprotein-cholesterol (HDL-C) from the baseline to the end of period 4.

Other efficacy measures included percent changes across dose ranges in all treatment groups in apolipoprotein B (apo B) cholesterol, apo A cholesterol, non-HDL-C, and triglyc-erides. The average LDL-C levels at the baseline across the treatment groups ranged from 179 to 181 mg/dl.

After six weeks of therapy, the patients taking EZE 10 mg plus simvastatin 10 mg and EZE 10 mg plus simvastatin 20 mg experienced LDL-C reductions of 46% and 50%, respectively, compared with the significantly lower reduction in HDL-C levels with atorvastatin alone (37%).

The investigators also doubled the respective statin doses up to a maximum of 80 mg for each treatment group. EZE plus simvastatin consistently provided greater reductions of LDL-C than did canadian atorvastatin at all points in the treatment period. Furthermore, the EZE/simvastatin combination further improved the other lipid and lipoprotein parameters studied.

Ximelgantran for Stroke Prevention in Nonvalvular Atrial Fibrillation

Speaker: Jonathan L. Halperin, MD, Professor of Medicine and Director of Cardiology Clinical Services, The Zena and Michael A. Wiener Cardiovascular Institute and Henry R. Kravis Center for Cardiovascular Health, Mount Sinai Medical Center, New York, New York.

Pooled data from two phase III stroke-prevention trials demonstrated that ximelgantran (Exantra®, AstraZeneca), an oral direct thrombin inhibitor, administered without coagulation monitoring or dose adjustments, was at least as effective as warfarin for preventing stroke and systemic embolic events. It was also associated with less bleeding than the current treatment with adequately controlled warfarin in both men and women with nonvalvular atrial fibrillation.

Although nonvalvular atrial fibrillation affects women less often than men, the risk of stroke is greater among women.

This analysis of the Stroke Prevention by Oral Thrombin

Inhibitor in Atrial Fibrillation (SPORTIF) III and IV non-inferiority trials compared the efficacy and safety of 5,075 men and 2,257 women with atrial fibrillation. These patients received either a fixed dose of ximelgantran at 36 mg twice daily or an adjusted dose of canadian warfarin, with a target International Normalized Ratio (INR) of 2.0-3.0.

During 11,233 patient-years and exposure over a mean of 19 months, the results were as follows:

  • Women receiving ximelgantran experienced 72 primary events at a rate of 2.2% per year; women taking warfarin showed a rate of 2.0% per year.
  • Men taking ximelgantran experienced 112 primary events at a rate of 1.4% per year; men receiving warfarin experienced a rate of 1.5% per year.

Ximelagantran, however, was associated with a lower incidence of bleeding in both men and women compared with warfarin, but the overall combined rates of major and minor hemorrhages were greater among women. Results were as follows:

  • In women taking ximelgantran, the incidence of major and minor bleeding was 35.4%; for men receiving ximel-gantran, it was 30.1% per year.
  • For women who were treated with warfarin, the rate of bleeding was 44.8%; for men taking, the incidence was 36.3% per year.


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