Meeting Perspectives: American College of Cardiology, Part 1

Commentary by Rob Donnino MD, NYU Division of Cardiology

The annual meeting of the ACC was held last month in Chicago. A good number of NYU faculty and fellows either presented at or attended the meetings. The cardiology fellows exhibited an impressive balance between exploring the Chicago nightlife and diligent attendance at the meetings. Several of the cardiology fellows presented some of the highlights of the ACC meeting at a recent journal club conference for the Cardiology Division. They will be summarized in a three part weekly series. Part 1 follows below:

Dr. Sohah Iqbal reported the results of the ENHANCE trial. This trial randomized 720 patients with familial hypercholesterolemia to receive either simvastatin alone or in combination with ezetimibe. The primary outcome, change in carotid-artery intima-media thickness (IMT), did not differ between the two groups after 2 years of treatment. This lack of effect was present despite a more significant lowering of LDL (and elevation of HDL) in the combination simvastatin/ezetimibe group. At the end of the study, the LDL in the combination group was 141 mg/dl vs. 192 in the simvastatin alone group.

As many of you know, the ENHANCE trial has generated considerable discussion both in and outside of the medical community, by both the lay press and even by members of the U.S. Congress. Some of the controversy began even before the results were reported when the drug company involved in the study was accused of delaying the reporting of the results. While this matter is currently under Congressional investigation, we will stick with a discussion of the medical results…

At first glance, the results of this trial are both disappointing and somewhat surprising. Prior trials have overwhelmingly demonstrated positive outcomes in patients with significant lowering of LDL. However, several criticisms have been raised with regard to the methodology used in this study. First, there is some controversy over the appropriateness of using IMT as a primary endpoint. While IMT does correlate with the degree of coronary atherosclerosis, it is not a perfect surrogate. That being said, prior studies using statins have shown a halt of IMT progression and even regression in patients after LDL lowering. Some have criticized the choice of the patient population (heterozygotes of familial hypercholesterolemia), and have pointed out that even after treatment for 24 months, the mean LDL was 140 in the simvastatin/ezetimibe group. Yet, again, there has been at least one trial in which a statin did show a halt in IMT progression in this population.

Another major criticism of this report is the fact that an overwhelming majority of patients were on lipid lowering agents prior to enrollment. This may explain why the starting mean IMT (7 mm) is somewhat lower than in prior studies in this population. Some argue that prior statin treatment could have blunted any further plaque regression that might have been seen with the addition of ezetimibe.

Despite all of the methodological concerns of this study, the expert panel at the ACC recommended using ezetimibe only after the addition of niacin, bile acid sequesters, and/or fibrates (in no specific order) to maximal statin therapy. While I think most clinicians would agree with the need to maximize statin dosing before turning to other agents, some will likely continue to use ezetimibe as a second-line agent given its ease of use, good safety profile, and excellent tolerability. Ultimately we will all have to wait for the large randomized trials currently underway to evaluate the effect of ezetimibe on hard clinical endpoints. Unfortunately, the first of these trials is expected to be completed no earlier than 2010.

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