使用statin 類藥物來減少低密度脂蛋白- 膽固醇 (LDL-C) 是預防和治療動脈粥狀硬化性 心血管疾病 (ASCVD) 的最關鍵措施之一。然而在給予statin 甚至強化劑量治療的患者，我們 觀察到可觀的殘餘風險存在，而且也有不少病人未達建議的LDL-C 標的，或者因藥物副作用 而停藥。因此需要其他異於statin 的藥理策略來治療高血脂症。有人提出LDL-C 低於目前建 議水準可能獲得額外的臨床效益，而不會影響病人安全的看法。延伸此一概念，前蛋白轉化 酶枯草溶菌素9 (PCSK9) 抑制劑 alirocumab 在三期臨床試驗能使患者達到非常低的LDL-C 水 準，但尚無長期結局和安全性的資料。FOURIER 研究是針對在ASCVD 病人在已給予statin 的基礎上，測試evolocumab 的臨床療效和安全性。FOURIER 研究的結果是令人振奮的，有 可能影響未來降脂治療範式，然而由於成本效益分析並不如預期，此結果是否能應用於臨床 實踐引人高度關注。

Low-density lipoprotein-cholesterol (LDL-C) reduction with statin therapy is one of the most pivotal interventions for atherosclerotic cardiovascular disease (ASCVD) prevention and treatment. Nevertheless, a substantial “residual cardiovascular risk” is observed in patients on statin treatment, even undergoing intensive statin regimens. Furthermore, a sizable proportion of statin-treated patients do not achieve recommended target LDL-C levels, and some discontinue treatment owing to drug-related side effects. Therefore, additional pharmacological strategies beyond statin to treat dyslipidemia are needed. It has been proposed that lower LDL-C levels than those currently recommended may provide additional clinical benefit without adversely impacting patient safety. In extending this concept, the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors alirocumab allows patients to achieve very low LDL-C levels in phase 3 trials, but without outcomes or long-term safety data. FOURIER was a dedicated cardiovascular outcomes trial that tested the clinical efficacy and safety of evolocumab on a background of statin therapy in patients with clinically evident ASCVD. The inspiring results of FOURIER trial are likely to impact on future treatment paradigms. However, since FOURIER trial fell short of expectations about it’s cost- effectiveness, whether it comes to implement the trial results into clinical practice is highly concerned. (J Intern Med Taiwan 2017; 28: 261-270)