最近完成的IMPROVE-IT研究指出近期發生急性冠心症的高風險人群中,將ezetimibe加入simvastatin與單用simvastatin比較,還能進一步減少心血管事件。這是第一次有臨床研究表明在statin的基礎下加入另一非statin藥物能有顯著臨床效益。特別是IMPROVE-IT研究顯示低密度脂蛋白膽固醇(LDL-C)降幅與心血管事件減少之間的量效呈正比關係,符合膽固醇治療試驗統合分析的結果所預期。然而卻不能解讀在本研究中的ezetimibe有獨到之處,實際上,其真正含義是提示我們如能有效降低LDL-C,無論何種機制都有相同效益。這些資料也充分地強化了膽固醇學說,並證明LDL-C是預估心血管預後最重要的替代性指標。此外該研究表明將現行準則所建議的LDL-C目標值額外再降低,還能進一步減少心血管事件而且具安全性。總合這些結果在臨床實務中對降低LDL-C與心血管風險間關係的進一步了解至關重要。IMPROVE-IT研究代表著降血脂策略下一步驟的里程碑,而非最後的進展,需要後續的不斷努力,才能使降血脂治療達到減少心血管風險的最理想效果。
In the recently completed IMPROVE-IT trial, adding ezetimibe to simvastatin in a high-risk population with a recent acute coronary syndrome significantly reduced the risk of cardiovascular (CV) events relative to simvastatin alone. It is the first clinical trial to show a benefit of adding a non-statin lipid-modifying agent to statin therapy. Specifically, IMPROVE-IT trial demonstrates that ezetimibe added to a statin provides an incremental reduction in CV risk proportional to its ability to lower low density lipoprotein- cholesterol (LDL-C), as that predicted by the Cholesterol Treatment Trialists metaanalysis of statin trials. However, IMPROVE-IT trial should not be interpreted as showing anything uniquely beneficial about the use of ezetimibe. Indeed, the real implication of this trial is to suggest that all reductions in LDL-C levels, regardless of mechanism, are of equivalent benefit. These data also substantially reinforces the cholesterol theory, and proves that LDL-C is the most important surrogate marker for predicting CV outcomes. In addition, they demonstrate that even greater CV risk reductions can be safely achieved with additional reductions in LDL-C below the currently recommended goal. Taken together, the results are relevant to a better understanding of the relationship between LDL-C and CV risk and to clinical practice. IMPROVE-IT trial represents a milestone to establish the next step of lipid lowering strategy, but likely not the last advance in the on-going effort to achieve optimal CV risk reductions through lipid lowering therapy.