Meta-analysis suggests no link between anti-VEGF and severe cardiovascular events

This study found that ranibizumab and bevacizumab were not associated with significant increases in major cardiovascular or nonocular hemorrhagic events, although higher-powered studies are needed to confirm this.

To the authors’ knowledge, this is the first systematic review and meta-analysis to specifically investigate systemic cardiovascular and hemorrhagic adverse events associated with intravitreal administration of anti-VEGF monoclonal antibodies in a large population of patients included in randomized clinical trials.

They compared rates of major cardiovascular and nonocular hemorrhagic events after ranibizumab and bevacizumab treatment in patients with AMD, diabetic macular edema and retinal vein occlusions. Their analysis included 21 randomized trials involving 9,557 patients.

Ranibizumab and bevacizumab did not significantly increase the risk of major cardiovascular events or nonocular hemorrhagic events compared with control treatments (sham, laser and other non-anti-VEGF interventions). Also they did not increase risk of overall mortality, cardiovascular mortality, stroke, myocardial infarction or hypertension. However, bevacizumab increased the risk of venous thromboembolic events and ranibizumab increased the risk of nonocular hemorrhagic events in patients with AMD. 

The authors note that cardiovascular and hemorrhagic events were secondary safety outcomes in the studies examined, and therefore subject to potential detection or reporting bias. These biases were difficult to evaluate because the included studies contained limited information on how adverse events were reported.

Furthermore, the studies were small and therefore not powered sufficiently to show an increase in adverse events risk. They say that the multiplicity of comparisons in this meta-analysis could have led to spurious findings, and the long-term effect of these treatments beyond two years still needs to be evaluated.