Cerebrovascular accidents in patients treated for choroidal neovascularization with ranibizumab in randomized controlled trials

• Published in: Retina (Philadelphia, Pa.) Vol. 32; no. 9; p. 1821
• Main Authors: Bressler, Neil M, Boyer, David S, Williams, David F, Butler, Steven, Francom, Steven F, Brown, Benton, Di Nucci, Flavia, Cramm, Timothy, Tuomi, Lisa L, Ianchulev, Tsontcho, Rubio, Roman G
• Format: Journal Article
• Language: English
• Published: United States 01.10.2012
• Subjects: Angiogenesis Inhibitors - administration & dosage; Angiogenesis Inhibitors - adverse effects; Antibodies, Monoclonal, Humanized - administration & dosage; Antibodies, Monoclonal, Humanized - adverse effects; Choroidal Neovascularization - drug therapy; Humans; Intravitreal Injections; Odds Ratio; Randomized Controlled Trials as Topic; Ranibizumab; Risk Factors; Stroke - chemically induced; Stroke - diagnosis; Vascular Endothelial Growth Factor A - antagonists & inhibitors; Wet Macular Degeneration - drug therapy
• ISSN: 1539-2864
• DOI: 10.1097/IAE.0b013e31825db6ba

To analyze cerebrovascular accidents (CVAs) pooled from large, randomized, controlled clinical trials of ranibizumab treatment for neovascular age-related macular degeneration. Events in five trials (FOCUS, MARINA, ANCHOR, PIER, and SAILOR) were analyzed using a standard safety monitoring process. Exact methods, stratified by study, were used to test for treatment differences based on odds ratios. A stepwise logistic regression model was fit to classify subjects' risk for CVA based on medical history. Treatment differences in CVA rates at 1 year or 2 years were evaluated within risk groups using stratified exact methods. Pooled 2-year CVA rates were <3%; odds ratios (95% confidence intervals) for CVA risk were 1.2 (0.4-4.4) for ranibizumab 0.3-mg versus control, 2.2 (0.8-7.1) for 0.5 mg versus control, and 1.5 (0.8-3.0) for 0.5-mg versus 0.3-mg ranibizumab. No substantial increased risk of CVA for 0.5 mg versus 0.3 mg was identified in pooled analyses or any of the individual trials. In pooled analyses, the difference between 0.5-mg ranibizumab and control was larger (7.7 [1.2-177]) among high-risk CVA patients. This analysis provided some evidence, although not definitive, of a potential increased risk of CVA with ranibizumab versus control or with 0.5-mg versus 0.3-mg ranibizumab. Continued monitoring for CVA within clinical trials seems warrented.