Pratt Nicole L, Ramsay Emmae N, Kemp Anna, Kalisch-Ellett Lisa M, Shakib Sepehr, Caughey Gillian E, Ryan Philip, Graves Stephen, Roughead Elizabeth E
School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA, Australia,
Drug Saf. 2014 Dec;37(12):1021-7. doi: 10.1007/s40264-014-0231-2.
Ranibizumab, a vascular endothelial growth factor (VEGF) inhibitor, is used in the treatment of age-related macular degeneration. Inhibition of VEGF has an anti-angiogenic action and is associated with thrombogenicity, thus, myocardial infarction and ischaemic stroke are potential side effects of VEGF inhibitors.
Our objective was to assess the association between use of ranibizumab and risk of hospitalisation for ischaemic stroke (IS) and myocardial infarction (MI).
The self-controlled case series design was used, including subjects exposed to ranibizumab (Anatomical Therapeutic Chemical [ATC] code S01LA04) who were hospitalized for IS (International Classification of Diseases, tenth edition [ICD-10] code I63) or the combined endpoint of stroke or transient ischaemic attack (TIA) (ICD-10 code G45) or MI (ICD-10 code I21) were identified between August 2007 and March 2013. Rate ratios in exposed periods compared with unexposed periods were calculated using conditional Poisson regression.
A total of 323 subjects received ranibizumab and were hospitalized for IS, 490 for IS or TIA, and 391 for MI. Median period of exposure was 8-9 months with follow-up times of approximately 2.8 years. No elevated risk of IS was seen in the 1-30 days post initiation (incidence rate ratio [IRR] 1.36; 95% confidence interval [CI] 0.98-1.88); however, elevated risk was observed for those who received therapy for 31-60 days (IRR 1.91; 95% CI 1.13-3.24). Sensitivity analyses adjusting for time-varying confounders found elevated risk in both the 1-30 days and 31-60 days periods. Similar results to those for IS were observed for the combined endpoint of IS or TIA. No association was seen for MI in either time period (1-30 days IRR 0.90, 95% CI 0.65-1.23; 31-60 days IRR 0.98, 95% CI 0.54-1.79).
This case-series analysis suggests an increased risk of hospitalisation for ischaemic stroke for patients receiving ranibizumab in the 31-60 days risk period. Studies with larger populations are required to confirm the risk in the 1-30 days risk period. No evidence of increased risk of hospitalisation for MI was observed.
雷珠单抗是一种血管内皮生长因子（VEGF）抑制剂，用于治疗年龄相关性黄斑变性。抑制VEGF具有抗血管生成作用，并与血栓形成有关，因此，心肌梗死和缺血性中风是VEGF抑制剂的潜在副作用。
我们的目的是评估使用雷珠单抗与缺血性中风（IS）和心肌梗死（MI）住院风险之间的关联。
采用自我对照病例系列设计，纳入使用雷珠单抗（解剖治疗化学分类代码[S01LA04]）并因IS（国际疾病分类第十版[ICD-10]代码I63）或中风或短暂性脑缺血发作（TIA）的联合终点（ICD-10代码G45）或MI（ICD-10代码I21）住院的患者，研究时间为2007年8月至2013年3月。使用条件泊松回归计算暴露期与非暴露期的发病率比。
共有323名接受雷珠单抗治疗的患者因IS住院，490名因IS或TIA住院，391名因MI住院。中位暴露期为8 - 9个月，随访时间约为2.8年。在开始治疗后的1 - 30天内，未观察到IS风险升高（发病率比[IRR] 1.36；95%置信区间[CI] 0.98 - 1.88）；然而，接受治疗31 - 60天的患者风险升高（IRR 1.91；95% CI 1.13 - 3.24）。对随时间变化的混杂因素进行调整的敏感性分析发现，在1 - 30天和31 - 60天期间风险均升高。IS或TIA联合终点的结果与IS相似。在两个时间段内MI均未发现关联（1 - 30天IRR 0.90，95% CI 0.65 - 1.23；31 - 60天IRR 0.98，95% CI 0.54 - 1.79）。
本病例系列分析表明，在31 - 60天风险期接受雷珠单抗治疗的患者缺血性中风住院风险增加。需要更大规模人群的研究来证实1 - 30天风险期的风险。未观察到MI住院风险增加的证据。
