PDF(Pubmed)
Abstract：
UNASSIGNED: Statins reduce low-density lipoprotein cholesterol (LDL-C) and are efficacious in the prevention of atherosclerotic cardiovascular disease (ASCVD). Dose-response to statins varies among patients and can be modeled using three distinct pharmacological properties: (1) E0 (baseline LDL-C), (2) ED50 (potency: median dose achieving 50% reduction in LDL-C); and (3) Emax (efficacy: maximum LDL-C reduction). However, individualized dose-response and its association with ASCVD events remains unknown.
UNASSIGNED: We analyze the relationship between ED50 and Emax with real-world cardiovascular disease outcomes.
UNASSIGNED: We leveraged de-identified electronic health record data to identify individuals exposed to multiple doses of the three most commonly prescribed statins (atorvastatin, simvastatin, or rosuvastatin) within the context of their longitudinal healthcare. We derived ED50 and Emax to quantify the relationship with a composite outcome of ASCVD events and all-cause mortality.
UNASSIGNED: We estimated ED50 and Emax for 3,033 unique individuals (atorvastatin: 1,632, simvastatin: 1,089, and rosuvastatin: 312) using a nonlinear, mixed effects dose-response model. Time-to-event analyses revealed that ED50 and Emax are independently associated with the primary endpoint. Hazard ratios were 0.85 (p < 0.01), 0.83 (p < 0.01), and 0.87 (p = 0.10) for ED50 and 1.13 (p < 0.001), 1.06 (p < 0.001), and 1.15 (p = 0.009) for Emax in the atorvastatin, simvastatin, and rosuvastatin cohorts, respectively.
UNASSIGNED: The class-wide association of ED50 and Emax with clinical outcomes indicates that these measures influence the risk for ASCVD events in patients on statins.
UNASSIGNED: We analyze the relationship between ED50 and Emax with real-world cardiovascular disease outcomes.
UNASSIGNED: We leveraged de-identified electronic health record data to identify individuals exposed to multiple doses of the three most commonly prescribed statins (atorvastatin, simvastatin, or rosuvastatin) within the context of their longitudinal healthcare. We derived ED50 and Emax to quantify the relationship with a composite outcome of ASCVD events and all-cause mortality.
UNASSIGNED: We estimated ED50 and Emax for 3,033 unique individuals (atorvastatin: 1,632, simvastatin: 1,089, and rosuvastatin: 312) using a nonlinear, mixed effects dose-response model. Time-to-event analyses revealed that ED50 and Emax are independently associated with the primary endpoint. Hazard ratios were 0.85 (p < 0.01), 0.83 (p < 0.01), and 0.87 (p = 0.10) for ED50 and 1.13 (p < 0.001), 1.06 (p < 0.001), and 1.15 (p = 0.009) for Emax in the atorvastatin, simvastatin, and rosuvastatin cohorts, respectively.
UNASSIGNED: The class-wide association of ED50 and Emax with clinical outcomes indicates that these measures influence the risk for ASCVD events in patients on statins.
摘要：
■他汀类药物可降低低密度脂蛋白胆固醇（LDL-C），可有效预防动脉粥样硬化性心血管疾病（ASCVD）。他汀类药物的剂量反应因患者而异，可以使用三种不同的药理学特性进行建模：（1）E0（基线LDL-C），(2)ED50(效力:实现LDL-C降低50%的中值剂量);和(3)Emax(功效:最大LDL-C降低)。然而,个体化剂量反应及其与ASCVD事件的关联尚不清楚.
■我们分析了ED50和Emax与真实世界心血管疾病结局之间的关系。
■我们利用去识别的电子健康记录数据来识别暴露于多剂量三种最常用的他汀类药物（阿托伐他汀，辛伐他汀,或瑞舒伐他汀)在其纵向医疗保健的背景下。我们推导了ED50和Emax来量化与ASCVD事件和全因死亡率的复合结局的关系。
■我们估计了3,033个独特个体的ED50和Emax（阿托伐他汀：1,632，辛伐他汀：1,089和瑞舒伐他汀：312）使用非线性，混合效应剂量-反应模型。事件时间分析显示ED50和Emax与主要终点独立相关。危险比为0.85(p<0.01)，0.83(p<0.01)，ED50和1.13(p<0.001)为0.87(p=0.10)，1.06（p<0.001），阿托伐他汀的Emax为1.15（p=0.009），辛伐他汀,和瑞舒伐他汀队列，分别。
■ED50和Emax与临床结局的全类关联表明，这些指标影响他汀类药物患者发生ASCVD事件的风险。
■我们分析了ED50和Emax与真实世界心血管疾病结局之间的关系。
■我们利用去识别的电子健康记录数据来识别暴露于多剂量三种最常用的他汀类药物（阿托伐他汀，辛伐他汀,或瑞舒伐他汀)在其纵向医疗保健的背景下。我们推导了ED50和Emax来量化与ASCVD事件和全因死亡率的复合结局的关系。
■我们估计了3,033个独特个体的ED50和Emax（阿托伐他汀：1,632，辛伐他汀：1,089和瑞舒伐他汀：312）使用非线性，混合效应剂量-反应模型。事件时间分析显示ED50和Emax与主要终点独立相关。危险比为0.85(p<0.01)，0.83(p<0.01)，ED50和1.13(p<0.001)为0.87(p=0.10)，1.06（p<0.001），阿托伐他汀的Emax为1.15（p=0.009），辛伐他汀,和瑞舒伐他汀队列，分别。
■ED50和Emax与临床结局的全类关联表明，这些指标影响他汀类药物患者发生ASCVD事件的风险。
