Louisville Metabolic and Atherosclerosis Research Center, Louisville, KY, USA.
Merck & Co, Inc, Kenilworth, NJ, USA.
J Clin Lipidol. 2017 Jul-Aug;11(4):929-937. doi: 10.1016/j.jacl.2017.04.121. Epub 2017 May 8.
The 2008 Ezetimibe and Simvastatin in Hypercholesterolemia Enhances Atherosclerosis Regression (ENHANCE) study demonstrated ezetimibe + simvastatin vs simvastatin alone had a neutral effect on the surrogate endpoint of carotid intima-media thickness. Subsequent media portrayal of the study prompted ezetimibe discontinuation in many patients.
The objective of the study was to assess the impact of ENHANCE reporting on ezetimibe discontinuation, low-density lipoprotein cholesterol (LDL-C) changes, and potential cardiovascular disease (CVD) risk.
This analysis used claims data in a retrospective, observational study of patients receiving ezetimibe + statin and compared LDL-C for patients who discontinued ezetimibe (n = 970) vs those who continued ezetimibe + statins (n = 3706) after ENHANCE results disclosure. Change in relative CVD risk was estimated from the absolute LDL-C difference between groups per the Cholesterol Treatment Trialists' meta-analysis of statin trials.
The rate of ezetimibe discontinuation was 2% in the 6 months before and 21% in the 6 months after reporting of ENHANCE results. Among patients who ultimately discontinued vs continued ezetimibe, respective mean LDL-C levels were 79.8 and 78.3 mg/dL 6 months before reporting of the ENHANCE results and 93.5 and 78.1 mg/dL 6 months after reporting of ENHANCE. Predictive application of the Cholesterol Treatment Trialists' meta-analysis suggested the 13.9 mg/dL increase in mean LDL-C translated to a 9.4% increase in relative CVD risk for those who discontinued ezetimibe.
After reporting of the neutral ENHANCE results, ezetimibe discontinuation rate increased, LDL-C levels increased, and predicted CVD risk increased among those who discontinued ezetimibe. Characterization of clinical outcomes regarding lipid-altering agents based on surrogate biomarker studies not designed to assess CVD outcomes may be misleading, potentially placing patients at increased CVD risk.
2008 年依折麦布和辛伐他汀在高胆固醇血症中增强动脉粥样硬化消退（ENHANCE）研究表明，依折麦布+辛伐他汀与辛伐他汀单药治疗相比，对颈动脉内膜中层厚度的替代终点没有影响。随后媒体对该研究的报道促使许多患者停用了依折麦布。
本研究旨在评估 ENHANCE 报告对依折麦布停药、低密度脂蛋白胆固醇（LDL-C）变化以及潜在心血管疾病（CVD）风险的影响。
本分析使用了接受依折麦布+他汀类药物治疗的患者的索赔数据，进行了一项回顾性观察性研究，并比较了在 ENHANCE 结果公布后停止使用依折麦布（n=970）和继续使用依折麦布+他汀类药物（n=3706）的患者的 LDL-C。根据他汀类药物试验的胆固醇治疗试验者荟萃分析，通过两组间的绝对 LDL-C 差异估计相对 CVD 风险的变化。
在报告 ENHANCE 结果的前 6 个月，依折麦布停药率为 2%，在报告后的 6 个月为 21%。在最终停止和继续使用依折麦布的患者中，分别在报告 ENHANCE 结果的前 6 个月，各自的平均 LDL-C 水平为 79.8 和 78.3mg/dL，在报告后的 6 个月为 93.5 和 78.1mg/dL。胆固醇治疗试验者荟萃分析的预测应用表明，平均 LDL-C 升高 13.9mg/dL 会导致停止使用依折麦布的患者相对 CVD 风险增加 9.4%。
在报告中性的 ENHANCE 结果后，依折麦布的停药率增加，LDL-C 水平升高，停止使用依折麦布的患者预测 CVD 风险增加。基于设计用于评估 CVD 结局的替代生物标志物研究来描述降脂药物的临床结局可能会产生误导，从而使患者面临更高的 CVD 风险。
