Trillenberg Peter, Katalinic Alexander, Thern Julia, Graf Tobias
Department of Neurology, University Hospital of Schleswig-Holstein, Campus Lübeck, Lübeck, Germany.
Institute of Social Medicine and Epidemiology, University of Lübeck, Lübeck, Germany.
Eur J Neurol. 2021 Sep;28(9):2965-2970. doi: 10.1111/ene.14996. Epub 2021 Jul 9.
Some groups of cardiovascular drugs (beta-blocking drugs, Ca antagonists, antiarrhythmics) are listed as potentially worsening myasthenia. An empirical basis for alternative recommendations for antihypertensive and antiarrhythmic therapy in myasthenia patients has not yet been provided.
From the World Health Organization pharmacovigilance database, we retrieved total and myasthenia-related counts of adverse drug reactions for various groups of drugs used in cardiovascular disease and drugs with related mechanism of action used in other indications. We calculated the reporting odds ratio as a measure of a disproportional fraction of myasthenia-related events among all events. A 95% confidence interval of reporting odds ratio (ROR) >1 was taken as an indication for a higher risk. Because our approach involves a considerable number of tests, this situation is referred to as a signal that requires additional confirmation.
A signal for an increased risk was noted for tizanidine, for alpha-blocking drugs, for beta-blocking drugs, and for Ca antagonists. ROR indicated a lower-than-average risk for salbutamol, angiotensin receptor antagonists, oral anticoagulants, thrombocytic function inhibitors, and heparins.
Angiotensin receptor antagonists, angiotensin-converting enzyme inhibitors, and diuretics seem to be safe in antihypertensive therapy. Surprisingly, and yet requiring confirmation by case reports, alpha receptor-blocking drugs seem to carry a risk of myasthenia worsening. Amiodarone seems to be a safe alternative in antiarrhythmic therapy in patients with myasthenia.
某些心血管药物类别（β受体阻滞剂、钙拮抗剂、抗心律失常药）被列为可能使重症肌无力病情恶化的药物。目前尚未为重症肌无力患者的抗高血压和抗心律失常治疗的替代建议提供实证依据。
从世界卫生组织药物警戒数据库中，我们检索了用于心血管疾病的各类药物以及用于其他适应症的具有相关作用机制的药物的药物不良反应总数及与重症肌无力相关的不良反应数。我们计算报告比值比，作为所有事件中与重症肌无力相关事件不成比例部分的一种衡量指标。报告比值比（ROR）的95%置信区间>1被视为风险较高的指标。由于我们的方法涉及大量检验，这种情况被称为需要额外确认的信号。
替扎尼定、α受体阻滞剂、β受体阻滞剂和钙拮抗剂出现了风险增加的信号。ROR表明沙丁胺醇、血管紧张素受体拮抗剂、口服抗凝剂、血小板功能抑制剂和肝素的风险低于平均水平。
血管紧张素受体拮抗剂、血管紧张素转换酶抑制剂和利尿剂在抗高血压治疗中似乎是安全的。令人惊讶的是，尽管需要病例报告予以证实，但α受体阻滞剂似乎有使重症肌无力病情恶化的风险。胺碘酮似乎是重症肌无力患者抗心律失常治疗中的一种安全替代药物。
