Impact of Adding Ezetimibe to Statin to Achieve Low-Density Lipoprotein Cholesterol Goal (from the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation [COURAGE] Trial).

Maron DJ, Hartigan PM, Neff DR, et al and COURAGE Trial Investigators.
Am J Cardiol. 2013 Mar 25. doi: 10.1016/j.amjcard.2013.02.005.

Background

The Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial was set up to compare the effects of intensive lifestyle and pharmacologic intervention (optimal medical therapy) with or without percutaneous coronary intervention (PCI). No different primary event rate was seen between the PCI group and the optimal medical therapy group (19.0% vs 18.5%, HR: 1.05 95%CI: 0.87-1.27, P=0.62)[1]. This report describes the results of aggressive therapy as part of the optimal medical therapy  to lower LDL cholesterol (LDL-C) to a prespecified target, focussing on the impact of adding ezetimibe to simvastatin. The primary lipid goal was initially (1997) set at LDL-C of 60-85 mg/dl, but adapted in 2004 to an optimal LDL-C of <70 mg/dl.

Main results

• When combining all COURAGE patients 49% had LDL-C < 100 mg/dl, 29% had LDL-C < 85 mg/dl and 14% had LDL-C < 70 mg/dl at baseline. After titration to the maximum tolerated statin doses, those numbers had improved to 66% for LDL-C < 100 mg/dl, 40% with LDL-C < 85 mg/dl and 23% with LDL-C < 70 mg/dl.
• Adding ezetimibe further increased the proportions of patients achieving the different goals to 83-85% with LDL-C < 100 mg/dl, 70-73% with LDL-C <85 mg/dl and 45-47% with LDL-C < 70 mg/dl.
• Statistically significant predictors for reaching the goals of LDL-C < 70 and < 85 mg/dl were lower baseline LDL-C, lower average statin dose and ezetimibe use. Ezetimibe was a more important contributor to the attainment of the lower LDL-C goal.

Conclusion

Adding ezetimibe to a maximum tolerated statin dose is very effective in order to reach LDL-C goals. Because the ENHANCE and ARBITER 6-HALTS trials did not provide evidence that ezetimibe has an impact on atherosclerosis progression, controversy surrounds the use of ezetimibe. The combination of simvastatin and ezetimibe has been shown to reduce the frequency of ischemic events. The efficacy of ezetimibe to prevent coronary events remains to be elucidated. Since the COURAGE trial did not randomise patients to statin therapy with or without ezetimibe, no conclusions can be drawn on the effect of ezetimibe on clinical outcome.

References

1. Boden WE, O’Rourke RA, Teo KK et al. The evolving pattern of symptomatic coronary artery disease in the United States and Canada: baseline characteristics of the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial. Am J Cardiol 2007;99:208e212.     

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