Brigham and Women's Hospital, Boston, Massachusetts; Baim Institute for Clinical Research, Boston, Massachusetts.
Regeneron Pharmaceuticals, Inc., Tarrytown, New York.
Am J Cardiol. 2019 Apr 15;123(8):1202-1207. doi: 10.1016/j.amjcard.2019.01.028. Epub 2019 Jan 25.
In a population with atherosclerotic cardiovascular disease, previous research indicated that approximately 86% can achieve low-density lipoprotein cholesterol (LDL-C) of <70 mg/dL with oral lipid-lowering therapies (LLT) only, whereas 14% would require a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor. We aim to estimate these values accounting for varying levels of statin intolerance. A simulation model described previously was used to estimate the utilization of LLT needed to achieve LDL-C <70 mg/dL via an intensification algorithm which maximized statins before adding ezetimibe or a PCSK9 inhibitor. The current analysis took into account varying background rates of statin intolerance. We defined statin intolerance as either partial (inability to tolerate high-intensity statin) or full (inability to tolerate any statin). With treatment intensification and 10% of patients having partial statin intolerance, the use of ezetimibe (± statin ± PCSK9 inhibitor) increased from 32.7% to 34.9%, and the need for a PCSK9 inhibitor (+ ezetimibe ± statin) increased from 14.0% to 15.5%. If, instead, 10% were fully statin intolerant, the use of ezetimibe (± statin ± PCSK9 inhibitor) increased from 32.7% to 38.5%, and the use of a PCSK9 inhibitor (+ ezetimibe ± statin) increased from 14.0% to 19.7%. In conclusion, in our simulation-based study, partial statin intolerance increased the need for nonstatins only modestly (by an absolute 2.2%), whereas having 10% of patients with full statin intolerance increased the need for PCSK9 inhibitors from 14% overall to approximately 20%.
在患有动脉粥样硬化性心血管疾病的人群中,先前的研究表明,仅通过口服降脂药物(LLT),约 86%的患者可以将低密度脂蛋白胆固醇(LDL-C)降至<70mg/dL,而 14%的患者需要使用前蛋白转化酶枯草溶菌素 9(PCSK9)抑制剂。我们旨在估计这些值,同时考虑到不同程度的他汀类药物不耐受。先前使用的模拟模型用于估计通过强化算法实现 LDL-C<70mg/dL 所需的 LLT 利用率,该算法在添加依折麦布或 PCSK9 抑制剂之前最大化他汀类药物的使用。当前的分析考虑了不同背景下他汀类药物不耐受的发生率。我们将他汀类药物不耐受定义为部分不耐受(无法耐受高强度他汀类药物)或完全不耐受(无法耐受任何他汀类药物)。通过治疗强化,10%的患者出现部分他汀类药物不耐受,依折麦布(±他汀类药物±PCSK9 抑制剂)的使用从 32.7%增加到 34.9%,需要使用 PCSK9 抑制剂(+依折麦布±他汀类药物)的比例从 14.0%增加到 15.5%。相反,如果 10%的患者完全不耐受他汀类药物,依折麦布(±他汀类药物±PCSK9 抑制剂)的使用从 32.7%增加到 38.5%,使用 PCSK9 抑制剂(+依折麦布±他汀类药物)的比例从 14.0%增加到 19.7%。总之,在我们的基于模拟的研究中,部分他汀类药物不耐受仅略微增加了对非他汀类药物的需求(绝对值增加 2.2%),而 10%的患者完全不耐受他汀类药物,使 PCSK9 抑制剂的总体需求从 14%增加到约 20%。