Ranibizumab and Risk of Hospitalisation for Ischaemic Stroke and Myocardial Infarction in Patients with Age-Related Macular Degeneration: A Self-Controlled Case-Series Analysis

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• 作者：Nicole L. Pratt (1) (6)
  Emmae N. Ramsay (1)
  Anna Kemp (2)
  Lisa M. Kalisch-Ellett (1)
  Sepehr Shakib (3)
  Gillian E. Caughey (1)
  Philip Ryan (4)
  Stephen Graves (5)
  Elizabeth E. Roughead (1)
  
• 刊名：Drug Safety
• 出版年：2014
• 出版时间：December 2014
• 年：2014
• 卷：37
• 期：12
• 页码：1021-1027
• 全文大小：221 KB
• 参考文献：1. Australian Medicines Handbook Pty Ltd. Australian medicines handbook. In: Rossi S, editor. Adelaide: Australian Medicines Handbook Pty Ltd; 2003.
  2. Tunon J, Ruiz-Moreno JM, Martin-Ventura JL, Blanco-Colio LM, Lorenzo O, Egido J. Cardiovascular risk and antiangiogenic therapy for age-related macular degeneration. Surv Ophthalmol. 2009;54(3):339-8. CrossRef
  3. Brown DM, Kaiser PK, Michels M, Soubrane G, Heier JS, Kim RY, et al. Ranibizumab versus verteporfin for neovascular age-related macular degeneration. N Eng J Med. 2006;355(14):1432-4. CrossRef
  4. Chang TS, Bressler NM, Fine JT, Dolan CM, Ward J, Klesert TR, et al. Improved vision-related function after ranibizumab treatment of neovascular age-related macular degeneration: results of a randomized clinical trial. Arch Ophthalmol. 2007;125(11):1460-. CrossRef
  5. Ueta T, Yanagi Y, Tamaki Y, Yamaguchi T. Cerebrovascular accidents in ranibizumab. Ophthalmology. 2009;116(2):362. CrossRef
  6. Schmucker C, Ehlken C, Agostini HT, Antes G, Ruecker G, Lelgemann M, et al. A safety review and meta-analyses of bevacizumab and ranibizumab: off-label versus goldstandard. PLoS One. 2012;7(8):e42701. CrossRef
  7. Bressler NM, Boyer DS, Williams DF, Butler S, Francom SF, Brown B, et al. Cerebrovascular accidents in patients treated for choroidal neovascularization with ranibizumab in randomized controlled trials. Retina. 2012;32(9):1821-.
  8. Curtis LH, Hammill BG, Schulman KA, Cousins SW. Risks of mortality, myocardial infarction, bleeding, and stroke associated with therapies for age-related macular degeneration. Arch Ophthalmol. 2010;128(10):1273-. CrossRef
  9. Kemp A, Preen DB, Morlet N, Clark A, McAllister IL, Briffa T, et al. Myocardial infarction after intravitreal vascular endothelial growth factor inhibitors: a whole population study. Retina. 2013;33(5):920-. CrossRef
  10. Campbell RJ, Gill SS, Bronskill SE, Paterson JM, Whitehead M, Bell CM. Adverse events with intravitreal injection of vascular endothelial growth factor inhibitors: nested case-control study. BMJ. 2012;345:e4203. CrossRef
  11. Campbell RJ, Bell CM, Paterson JM, Bronskill SE, Moineddin R, Whitehead M, et al. Stroke rates after introduction of vascular endothelial growth factor inhibitors for macular degeneration: a time series analysis. Ophthalmology. 2012;119(8):1604-. CrossRef
  12. Whitaker HJ, Farrington CP, Spiessens B, Musonda P. Tutorial in biostatistics: the self-controlled case series method. Stat Med. 2006;25(10):1768-797.
  13. Whitaker HJ, Hocine MC, Farrington CP. The methodology of self-controlled case series studies. Stat Methods Med Res. 2009;18:7-6. CrossRef
  14. Cohen SY, Dubois L, Tadayoni R, Fajnkuchen F, Nghiem-Buffet S, Delahaye-Mazza C, et al. Results of one-year’s treatment with ranibizumab for exudative age-related macular degeneration in a clinical setting. Am J Ophthalmol. 2009;148(3):409-3. CrossRef
  15. Geirsdottir A, Jonsson O, Thorisdottir S, Helgadottir G, Jonasson F, Stefansson E, et al. Population-based incidence of exudative age-related macular degeneration and ranibizumab treatment load. Br J Ophthalmol. 2012;96(3):444-. CrossRef
  16. Sloan K, Sales A, Liu C, Fishman P, Nichol P, Suzuki N, et al. Construction and characteristics of the RxRisk-V: a VA-adapted pharmacy-based case-mix instrument. Med Care. 2003;41(6):761-4.
  17. Farrington P, Whitaker H. Mortality and the self-controlled case series method: letter to the editor
• 作者单位：Nicole L. Pratt (1) (6)
  Emmae N. Ramsay (1)
  Anna Kemp (2)
  Lisa M. Kalisch-Ellett (1)
  Sepehr Shakib (3)
  Gillian E. Caughey (1)
  Philip Ryan (4)
  Stephen Graves (5)
  Elizabeth E. Roughead (1)
  
  1. School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA, Australia
  6. Quality Use of Medicines and Pharmacy Research Centre, University of South Australia, GPO Box 2471, Adelaide, SA, 5001, Australia
  2. Centre for Health Services Research, The University of Western Australia, Crawley, Australia
  3. Department of Clinical Pharmacology, Royal Adelaide Hospital, Adelaide, SA, Australia
  4. Data Management and Analysis Centre, Discipline of Public Health, University of Adelaide, Adelaide, SA, Australia
  5. Australian Orthopaedic Association National Joint Replacement Registry, Adelaide, SA, Australia
  
• ISSN：1179-1942

文摘

Background 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. Objective Our objective was to assess the association between use of ranibizumab and risk of hospitalisation for ischaemic stroke (IS) and myocardial infarction (MI). Methods 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. Results 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-?months with follow-up times of approximately 2.8?years. No elevated risk of IS was seen in the 1-0?days post initiation (incidence rate ratio [IRR] 1.36; 95?% confidence interval [CI] 0.98-.88); however, elevated risk was observed for those who received therapy for 31-0?days (IRR 1.91; 95?% CI 1.13-.24). Sensitivity analyses adjusting for time-varying confounders found elevated risk in both the 1-0?days and 31-0?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 (1-0?days IRR 0.90, 95?% CI 0.65-.23; 31-0?days IRR 0.98, 95?% CI 0.54-.79). Conclusion This case-series analysis suggests an increased risk of hospitalisation for ischaemic stroke for patients receiving ranibizumab in the 31-0?days risk period. Studies with larger populations are required to confirm the risk in the 1-0?days risk period. No evidence of increased risk of hospitalisation for MI was observed.