Purpose: To analyze cerebrovascular accidents (CVAs) pooled from large, randomized, controlled clinical trials of ranibizumab treatment for neovascular age-related macular degeneration.
Methods: 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.
Results: 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.
Conclusion: 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.