Clinical importance of the drug interaction between statins and CYP3A4 inhibitors: a retrospective cohort study in The Health Improvement Network
Clinical importance of the drug interaction between statins and CYP3A4 inhibitors: a retrospective cohort study in The Health Improvement Network
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DOI：
10.1002/pds.3199
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发表时间：
2012-05-01
影响因子：
2.6
通讯作者：
Strom, Brian L.
中科院分区：
文献类型：
--
作者：
Rowan, Christopher G.;Brunelli, Steven M.;Strom, Brian L.
目的比较他汀类药物与抑制CYP 3A 4同工酶的合并用药之间药物相互作用引起的肌肉毒性、肾功能不全和肝功能不全的相对危险性。不良事件的风险可能会加强伴随使用的药物，干扰他汀类metabolis.Methods从健康改善网络（THIN）从1990年至2008年的数据进行了回顾性队列研究。创建队列以独立评价每种结局（肌肉毒性、肾功能不全和肝功能不全）。每个队列包括新的他汀类药物启动者，并比较结果的相对风险。相互作用比（I*R）是主要关注的对比度。I*R代表每种他汀类药物（他汀类药物3A 4底物与他汀类药物非3A 4底物）与CYP 3A 4抑制剂的相对效应，与无CYP 3A 4抑制剂的他汀类药物的效应无关。我们调整了混杂变量使用多项倾向score.Results的平均随访时间为1.5年。在362 809例患者和792 665人-年中发生了7889起肌肉毒性事件。校正的肌肉毒性I*R为1.22（95%置信区间[CI] = 0.90-1.66）。在272，099例患者和574，584人-年中发生了1449起肾功能不全事件。校正的肾功能不全I*R为0.91（95% CI = 0.58-1.44）。在367612例患者和815945人-年中发生了1434起肝功能异常事件。校正后的肝功能损害I*R为0.78（95%CI = 0.45-1.31）。结论总体而言，本研究发现，与他汀类非3A 4底物联合CYP 3A 4抑制剂相比，使用他汀类3A 4底物的患者在肌肉毒性、肾功能不全或肝功能损害方面的相对风险无差异。版权所有（C）2012约翰威利父子有限公司
Objective To compare the relative hazard of muscle toxicity, renal dysfunction, and hepatic dysfunction associated with the drug interaction between statins and concomitant medications that inhibit the CYP3A4 isoenzyme.Background Although statins provide important clinical benefits related to mitigating the risk of cardiovascular events, this class of medications also has the potential for severe adverse reactions. The risk for adverse events may be potentiated by concomitant use of medications that interfere with statin metabolism.Methods Data from The Health Improvement Network (THIN) from 1990 to 2008 were used to conduct a retrospective cohort study. Cohorts were created to evaluate each outcome (muscle toxicity, renal dysfunction, and hepatic dysfunction) independently. Each cohort included new statin initiators and compared the relative hazard of the outcome. The interaction ratio (I*R) was the primary contrast of interest. The I*R represents the relative effect of each statin type (statin 3A4 substrate vs. statin non-3A4 substrate) with a CYP3A4 inhibitor, independent of the effect of the statin type without a CYP3A4 inhibitor. We adjusted for confounding variables using the multinomial propensity score.Results The median follow-up time per cohort was 1.5 years. There were 7889 muscle toxicity events among 362 809 patients and 792 665 person-years. The adjusted muscle toxicity I*R was 1.22 (95% confidence interval [CI] = 0.90-1.66). There were 1449 renal dysfunction events among 272,099 patients and 574 584 person-years. The adjusted renal dysfunction I*R was 0.91 (95% CI = 0.58-1.44). There were 1434 hepatic dysfunction events among 367 612 patients and 815 945 person-years. The adjusted hepatic dysfunction I*R was 0.78 (95% CI = 0.45-1.31).Conclusions Overall, this study found no difference in the relative hazard of muscle toxicity, renal dysfunction, or hepatic dysfunction for patients prescribed a statin 3A4 substrate versus a statin non-3A4 substrate with CYP3A4 inhibitor concomitancy. Copyright (C) 2012 John Wiley & Sons, Ltd.