Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Mail Stop C238, 12850 E. Montview Blvd, Aurora, CO, 80045, USA.
Department of Integrated Medical Science, Cardiology and Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton, FL, USA.
Am J Cardiovasc Drugs. 2023 Jan;23(1):67-76. doi: 10.1007/s40256-022-00552-7. Epub 2022 Oct 31.
Patients with atherosclerotic cardiovascular disease who require additional low-density lipoprotein cholesterol (LDL-C) lowering despite maximally tolerated statins have a significant unmet medical need and are at increased risk of future cardiovascular events and a reduced quality of life.
We aimed to estimate the percentage of cardiovascular events avoided following treatment with a fixed-dose combination of bempedoic acid plus ezetimibe (BA+EZE FDC) versus ezetimibe (EZE) in patients with atherosclerotic cardiovascular disease receiving maximally tolerated statins across a range of baseline LDL-C levels.
A Markov cohort simulation model estimated major adverse cardiovascular events avoided over a lifetime horizon among patients with atherosclerotic cardiovascular disease and baseline LDL-C levels from 80 to >200 mg/dL. BA+EZE FDC was compared with EZE based on mean percent LDL-C reductions versus placebo reported in a phase III trial. Health outcomes for the average patient were extrapolated to a US population of 100,000 persons using evidence on contemporary LDL-C levels from the National Health and Nutrition Examination Survey.
Among patients with atherosclerotic cardiovascular disease not at the LDL-C goal with maximally tolerated statins, the addition of BA+EZE FDC compared with the addition of EZE was predicted to provide incremental absolute reductions in major adverse cardiovascular events dependent on baseline LDL-C levels at the population level. For those with baseline LDL-C of 101-110 mg/dL (n = 15,237), there were 4.9% (744) fewer events predicted, while for patients with baseline LDL-C of > 200 mg/dL (n = 1689), 10.9% (184) fewer events were predicted through the addition of BA+EZE FDC versus EZE.
Further LDL-C reductions through the addition of BA+EZE FDC to maximally tolerated statins are predicted to reduce major adverse cardiovascular events compared with the addition of EZE. Benefits are potentially greater among those with higher starting LDL-C.
尽管已接受最大耐受剂量的他汀类药物治疗，但仍需要进一步降低低密度脂蛋白胆固醇（LDL-C）的动脉粥样硬化心血管疾病患者存在显著未满足的医疗需求，并且未来发生心血管事件和降低生活质量的风险增加。
我们旨在评估在接受最大耐受剂量他汀类药物治疗的动脉粥样硬化性心血管疾病患者中，与依折麦布（EZE）相比，固定剂量联合应用贝匹达酸和依折麦布（BA+EZE FDC）治疗后可避免的心血管事件百分比，在一系列基线 LDL-C 水平下。
采用 Markov 队列模拟模型，在基线 LDL-C 水平为 80 至>200mg/dL 的动脉粥样硬化性心血管疾病患者中，估算一生中避免主要不良心血管事件的比例。根据 III 期试验中报告的与安慰剂相比的平均 LDL-C 降低百分比，BA+EZE FDC 与 EZE 进行比较。使用来自全国健康和营养检查调查的当代 LDL-C 水平的证据，将平均患者的健康结果外推到 100,000 名美国人群中。
在未达到最大耐受剂量他汀类药物治疗 LDL-C 目标的动脉粥样硬化性心血管疾病患者中，与添加 EZE 相比，添加 BA+EZE FDC 预测会根据人群中基线 LDL-C 水平，使主要不良心血管事件的绝对减少幅度有所增加。对于基线 LDL-C 为 101-110mg/dL 的患者（n=15237），预测可减少 4.9%（744）的事件，而对于基线 LDL-C>200mg/dL 的患者（n=1689），通过添加 BA+EZE FDC 与添加 EZE 相比，预测可减少 10.9%（184）的事件。
与添加 EZE 相比，通过添加 BA+EZE FDC 至最大耐受剂量的他汀类药物进一步降低 LDL-C 预计可减少主要不良心血管事件。对于基线 LDL-C 较高的患者，潜在获益可能更大。
