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Takashi Ueta, Yasuo Noda, Taku Toyama, Takuhiro Yamaguchi; Cerebrovascular risk by intravitreal injections of vascular endothelial growth factor inhibitors for age-related macular degeneration: systematic review of literature and meta-analysis. Invest. Ophthalmol. Vis. Sci. 2013;54(15):3172.
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To evaluate whether intravitreal injections of vascular endothelial growth factor (VEGF) inhibitors for age-related macular degeneration (AMD) increase the cerebrovascular, cardiovascular and mortality risk.
The design of the present study was a systematic review and meta-analysis of randomized controlled trials (RCTs) on ranibizumab. In addition, RCTs on aflibercept were also summarized. Data sources were Medline, Embase, Cochrane Library, and ClinicalTrials.gov. Studies were selected based on the predefined criteria for high quality randomized controlled trials (RCTs), including an enrollment of a minimum of 100 participants, with follow-up for at least one year, and follow-up completion in more than 80% of the enrolled subjects.
The first study selection yielded 317 articles on ranibizumab. After screening of the corresponding abstracts and full text papers, 6 trials totalling 4346 patients with exudative AMD were included. In patients treated with 0.5 mg ranibizumab the risk of CVAs was significantly higher than in patients treated with either 0.3 mg or no ranibizumab (RR 2.41, 95% CI 1.27-4.57). Furthermore, in patients treated monthly with ranibizumab the risk of CVAs was significantly higher (RR 2.79, 95% CI 1.19-6.54) than in patients treated infrequently (i.e., 0-3 times during month 3-11). The risk of MI and mortality were not affected by the intensity of ranibizumab treatment. In addition, aflibercept was significantly more associated with the incidence of CVA than ranibizumab (p=0.014).
Intravitreal injections of VEGF inhibitors could be associated with the increased risk of CVA, but not MI or mortality.
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