Primary Care Stratified Medicine (PRISM), Division of Primary Care, University of Nottingham, Nottingham, United Kingdom.
Centre for Medicine Optimisation Research and Education (CMORE), Research Department of Practice and Policy, UCL School of Pharmacy, London, United Kingdom.
PLoS One. 2021 Dec 2;16(12):e0260839. doi: 10.1371/journal.pone.0260839. eCollection 2021.
Variability in low-density lipoprotein cholesterol (LDL-C) response to statins is underappreciated. We characterised patients by their statin response (SR), baseline risk of cardiovascular disease (CVD) and 10-year CVD outcomes.
A multivariable model was developed using 183,213 United Kingdom (UK) patients without CVD to predict probability of sub-optimal SR, defined by guidelines as <40% reduction in LDL-C. We externally validated the model in a Hong Kong (HK) cohort (n = 170,904). Patients were stratified into four groups by predicted SR and 10-year CVD risk score: [SR1] optimal SR & low risk; [SR2] sub-optimal SR & low risk; [SR3] optimal SR & high risk; [SR4] sub-optimal SR & high risk; and 10-year hazard ratios (HR) determined for first major adverse cardiovascular event (MACE). Our SR model included 12 characteristics, with an area under the curve of 0.70 (95% confidence interval [CI] 0.70-0.71; UK) and 0.68 (95% CI 0.67-0.68; HK). HRs for MACE in predicted sub-optimal SR with low CVD risk groups (SR2 to SR1) were 1.39 (95% CI 1.35-1.43, p<0.001; UK) and 1.14 (95% CI 1.11-1.17, p<0.001; HK). In both cohorts, patients with predicted sub-optimal SR with high CVD risk (SR4 to SR3) had elevated risk of MACE (UK HR 1.36, 95% CI 1.32-1.40, p<0.001: HK HR 1.25, 95% CI 1.21-1.28, p<0.001).
Patients with sub-optimal response to statins experienced significantly more MACE, regardless of baseline CVD risk. To enhance cholesterol management for primary prevention, statin response should be considered alongside risk assessment.
人们对他汀类药物降低低密度脂蛋白胆固醇（LDL-C）反应的变异性认识不足。我们根据他汀类药物反应（SR）、心血管疾病（CVD）的基线风险和 10 年 CVD 结局对患者进行特征描述。
我们使用来自无 CVD 的 183213 名英国（UK）患者的多变量模型来预测指南定义的 LDL-C 降低<40%的低反应可能性，即亚最佳 SR。我们在香港（HK）队列（n=170904）中对该模型进行了外部验证。根据预测的 SR 和 10 年 CVD 风险评分，患者分为四组：[SR1]最佳 SR 和低风险；[SR2]低反应和低风险；[SR3]最佳 SR 和高风险；[SR4]低反应和高风险；并确定首次主要不良心血管事件（MACE）的 10 年危险比（HR）。我们的 SR 模型包含 12 个特征，曲线下面积为 0.70（95%置信区间[CI] 0.70-0.71；英国）和 0.68（95%CI 0.67-0.68；香港）。在预测低 CVD 风险组（SR2 至 SR1）的低 SR 中，MACE 的 HR 为 1.39（95%CI 1.35-1.43，p<0.001；英国）和 1.14（95%CI 1.11-1.17，p<0.001；香港）。在两个队列中，预测高 CVD 风险（SR4 至 SR3）的患者的 MACE 风险升高（英国 HR 1.36，95%CI 1.32-1.40，p<0.001；香港 HR 1.25，95%CI 1.21-1.28，p<0.001）。
无论基线 CVD 风险如何，他汀类药物反应不佳的患者发生 MACE 的风险显著增加。为了加强一级预防的胆固醇管理，应将他汀类药物反应与风险评估结合起来。
