Department of Medicine, University of California-San Diego School of Medicine, La Jolla, California 92093-0995, USA.
Pharmacotherapy. 2010 Jun;30(6):541-53. doi: 10.1592/phco.30.6.541.
To characterize the properties and natural history of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin)-associated muscle-related adverse effects (MAEs).
Patient-targeted postmarketing adverse-effect surveillance approach coupling survey design with an open-ended narrative.
University-affiliated health care system.
Three hundred fifty-four patients (age range 34-86 yrs) who self-reported muscle-related problems associated with statin therapy.
Patients with perceived statin-associated MAEs completed a survey assessing statin drugs and dosages; characteristics of the MAEs; time course of onset, resolution, or recurrence; and impact on quality of life (QOL). Cases were assessed for putative drug adverse-effect causality by using the Naranjo adverse drug reaction probability scale criteria and were evaluated for inclusion in groups for which mortality benefit with statins has been shown. Patients reported muscle pain (93%), fatigue (88%), and weakness (85%). Three hundred patients (85%) met literature criteria for probable or definite drug adverse-effect causality. Ninety-four percent of atorvastatin usages (240/255) generated MAEs versus 61% of lovastatin usages (38/62, p<0.0001). Higher potency statins reproduced MAEs in 100% of 39 rechallenges versus 73% (29/40) with lower potency rechallenges (p<0.01). Time course of onset after statin initiation varied (median 14 wks); some MAEs occurred after long-term symptom-free use. Recurrence with rechallenge had a significantly shorter latency to onset (median 2 wks). The MAEs adversely affected all assessed functional and QOL domains. Most patients with probable or definite MAEs were in categories for which available randomized controlled trial evidence shows no trend to all-cause mortality benefit with statin therapy.
This study complements available information on the properties and natural history of statin-associated MAEs, affirming dose dependence and strong QOL impact. The data indicating a dose-dependent relationship between MAE risk and recurrence suggest lower potency statins or discontinuation may bear consideration for ameliorating symptoms.
描述 3-羟基-3-甲基戊二酰辅酶 A 还原酶抑制剂（他汀类药物）相关肌肉不良事件（MAE）的性质和自然病史。
采用问卷调查设计与开放式叙述相结合的方法，对患者进行靶向的上市后不良事件监测。
大学附属医院医疗系统。
354 名（年龄 34-86 岁）报告他汀类药物治疗相关肌肉问题的患者。
有感知的他汀类药物相关 MAE 的患者完成了一份调查问卷，评估了他汀类药物药物和剂量；MAE 的特征；发病、缓解或复发的时间过程；以及对生活质量（QOL）的影响。使用 Naranjo 药物不良反应概率量表标准评估病例的潜在药物不良反应因果关系，并评估是否符合已证明他汀类药物具有生存获益的组别。患者报告肌肉疼痛（93%）、疲劳（88%）和虚弱（85%）。300 名患者（85%）符合文献中可能或明确的药物不良反应因果关系标准。阿托伐他汀的使用（240/255）产生 MAE 的比例为 94%，而洛伐他汀的使用（38/62）为 61%，差异具有统计学意义（p<0.0001）。更高效力的他汀类药物在 39 次再挑战中有 100%重现 MAE，而较低效力的他汀类药物再挑战中有 73%（29/40）重现（p<0.01）。他汀类药物起始后发病时间不同（中位数 14 周）；一些 MAE 发生在长期无症状使用后。再挑战时 MAE 的复发潜伏期明显缩短（中位数 2 周）。MAE 对所有评估的功能和 QOL 领域均有不利影响。大多数有明确或可能 MAE 的患者属于没有他汀类药物治疗全因死亡率获益趋势的随机对照试验证据类别。
本研究补充了他汀类药物相关 MAE 的性质和自然病史的现有信息，证实了剂量依赖性和对 QOL 的强烈影响。数据表明 MAE 风险与复发之间存在剂量依赖性关系，提示较低效力的他汀类药物或停药可能有助于改善症状。
