Department of Medicine, Drammen Hospital, Vestre Viken Hospital Trust, Dronninggata 28, Drammen 3004, Norway.
Department of Behavioural Sciences in Medicine, Faculty of Medicine, University of Oslo, Domus Medica, Sognsvannsveien 9, Oslo 0372, Norway.
Eur Heart J Cardiovasc Pharmacother. 2021 Nov 3;7(6):507-516. doi: 10.1093/ehjcvp/pvaa076.
To estimate the effect of atorvastatin on muscle symptom intensity in coronary heart disease (CHD) patients with self-perceived statin-associated muscle symptoms (SAMS) and to determine the relationship to blood levels of atorvastatin and/or metabolites.
A randomized multi-centre trial consecutively identified 982 patients with previous or ongoing atorvastatin treatment after a CHD event. Of these, 97 (9.9%) reported SAMS and 77 were randomized to 7-week double-blinded treatment with atorvastatin 40 mg/day and placebo in a crossover design. The primary outcome was the individual mean difference in muscle symptom intensity between the treatment periods, measured by visual-analogue scale (VAS) scores. Atorvastatin did not affect the intensity of muscle symptoms among 71 patients who completed the trial. Mean VAS difference (statin-placebo) was 0.31 (95% CI: -0.24 to 0.86). The proportion with more muscle symptoms during placebo than atorvastatin was 17% (n = 12), 55% (n = 39) had the same muscle symptom intensity during both treatment periods whereas 28% (n = 20) had more symptoms during atorvastatin than placebo (confirmed SAMS). There were no differences in clinical or pharmacogenetic characteristics between these groups. The levels of atorvastatin and/or metabolites did not correlate to muscle symptom intensity among patients with confirmed SAMS (Spearman's rho ≤0.40, for all variables).
Re-challenge with high-intensity atorvastatin did not affect the intensity of muscle symptoms in CHD patients with self-perceived SAMS during previous atorvastatin therapy. There was no relationship between muscle symptoms and the systemic exposure to atorvastatin and/or its metabolites. The findings encourage an informed discussion to elucidate other causes of muscle complaints and continued statin use.
评估阿托伐他汀对冠心病（CHD）伴自述他汀类药物相关肌肉症状（SAMS）患者肌肉症状严重程度的影响，并确定其与阿托伐他汀及/或代谢物血药水平的关系。
一项随机多中心试验连续纳入了 982 例 CHD 事件后接受阿托伐他汀既往或持续治疗的患者。其中 97 例（9.9%）报告有 SAMS，77 例按交叉设计随机分为 7 周阿托伐他汀 40mg/天和安慰剂双盲治疗期。主要结局为治疗期间个体肌肉症状严重程度的平均差异，采用视觉模拟量表（VAS）评分测量。71 例完成试验的患者中，阿托伐他汀并未影响肌肉症状的严重程度。平均 VAS 差值（他汀类药物-安慰剂）为 0.31（95%CI：-0.24 至 0.86）。在安慰剂期比阿托伐他汀期肌肉症状更严重的患者比例为 17%（n=12），55%（n=39）在两个治疗期的肌肉症状严重程度相同，而 28%（n=20）在阿托伐他汀期的肌肉症状比安慰剂期更严重（确诊 SAMS）。这些组之间的临床或药物遗传学特征无差异。在确诊 SAMS 的患者中，阿托伐他汀和/或代谢物的水平与肌肉症状严重程度之间无相关性（Spearman's rho ≤0.40，所有变量）。
在既往阿托伐他汀治疗期间有自述 SAMS 的 CHD 患者中，用高强度阿托伐他汀再治疗不会影响肌肉症状的严重程度。肌肉症状与阿托伐他汀及/或其代谢物的全身暴露之间没有关系。这些发现鼓励进行知情讨论，以阐明肌肉抱怨的其他原因，并继续使用他汀类药物。
