School of Pharmacy, University of Oslo, Oslo, Norway.
Mol Diagn Ther. 2011 Aug 1;15(4):221-7. doi: 10.1007/BF03256413.
Myopathic complaints are common in the general population and are more frequent with increasing age. When myopathic symptoms arise in a patient treated with a HMG-CoA reductase inhibitor (statin), it is always a question of whether the symptoms are due to statin-induced myopathy (SIM) or not (non-SIM). Diagnosis of SIM is not as straightforward as previously thought, because the most commonly used biomarker, serum creatine kinase, shows low specificity and selectivity, except in serious cases of rhabdomyolysis. There is a definite need for a novel biomarker for SIM.
Based on a previous study reporting an altered metabolic profile with increased systemic exposure to the suspected muscle-toxic metabolite atorvastatin lactone in patients with SIM compared with healthy controls, this study aimed to explore the use of atorvastatin metabolite measurements to diagnose muscular complaints during statin treatment as being either SIM or non-SIM. PATIENTS, SETTING, AND STUDY DESIGN: Fifty-three patients with self-reported myopathic symptoms during atorvastatin treatment were recruited from our outpatient clinic. The symptoms were clinically evaluated as being SIM or non-SIM, on the basis of atorvastatin re-challenge testing. Atorvastatin and its metabolites were measured at steady state in all patients and compared with the clinical evaluation to see if this could predict the outcome and hence be suitable as a diagnostic tool for SIM.
This was an exploratory study to investigate the proportion of patients correctly diagnosed by different metabolite cut-off ratios.
With a cut-off ratio set at 1.1 for the atorvastatin lactone to atorvastatin acid ratio, 15 of 28 SIM patients (sensitivity of 54%) and 20 of 24 non-SIM patients (specificity of 83%) were correctly diagnosed. This corresponds to a positive predictive value of 79% and a negative predictive value of 61% (p = 0.006).
The present study confirms an altered metabolic pattern of atorvastatin in patients with SIM and substantiates a central role of the lactone forms of statins in future investigations of statin myotoxicity. The atorvastatin lactone to acid ratio seems to be a valuable supportive diagnostic tool with high specificity and moderate sensitivity, adding to ordinary clinical evaluations when diagnosing SIM.
肌肉疾病的主诉在普通人群中很常见，并且随着年龄的增长而更加频繁。当接受 HMG-CoA 还原酶抑制剂（他汀类药物）治疗的患者出现肌肉疾病症状时，始终存在一个问题，即这些症状是否是由于他汀类药物引起的肌肉疾病（SIM）引起的。SIM 的诊断并不像以前想象的那么简单，因为最常用的生物标志物血清肌酸激酶除了在严重的横纹肌溶解症病例中外，特异性和选择性都较低。因此，我们确实需要一种新的 SIM 生物标志物。
基于之前的一项研究报告，与健康对照组相比，SIM 患者体内疑似肌肉毒性代谢物阿托伐他汀内酯的全身暴露增加，代谢谱发生改变，本研究旨在探索使用阿托伐他汀代谢产物测量来诊断他汀类药物治疗期间的肌肉主诉是否为 SIM 或非 SIM。
患者、设置和研究设计：从我们的门诊诊所招募了 53 名在阿托伐他汀治疗期间自述有肌肉疾病症状的患者。根据阿托伐他汀再挑战测试，对这些症状进行临床评估，判断是否为 SIM 或非 SIM。在所有患者的稳态下测量阿托伐他汀及其代谢物，并将其与临床评估进行比较，以观察其是否可以预测结果，从而作为 SIM 的诊断工具。
这是一项探索性研究，旨在调查不同代谢产物截止值的比例下，患者的正确诊断比例。
阿托伐他汀内酯与阿托伐他汀酸的比值设定为 1.1 时，28 名 SIM 患者中的 15 名（敏感性为 54%）和 24 名非 SIM 患者中的 20 名（特异性为 83%）被正确诊断。这对应于 79%的阳性预测值和 61%的阴性预测值（p=0.006）。
本研究证实了 SIM 患者阿托伐他汀代谢模式的改变，并证实了他汀类药物内酯形式在未来他汀类药物肌肉毒性研究中的核心作用。阿托伐他汀内酯与酸的比值似乎是一种有价值的支持性诊断工具，具有较高的特异性和中等敏感性，在诊断 SIM 时，可作为普通临床评估的补充。
