Cardiovascular risk in patients receiving ranibizumab for exudative age-related macular degeneration: A nationwide self-controlled case-series study

Aims To identify the association between ranibizumab and risk of stroke and acute myocardial infarction (AMI) in patients with exudative age-related macular degeneration (AMD). Methods We identified patients aged ≥45 years who received ranibizumab for exudative AMD from the Korean National Health Insurance database. Of these, we selected patients suffering stroke or AMI for the self-controlled case series. We estimated incidence rate ratios (IRR) for stroke or AMI by comparing incidence rates of ranibizumab-exposed periods to that of baseline using conditional Poisson regression. The risks of haemorrhagic and ischaemic strokes were also calculated separately. Results Among 33 134 patients receiving ranibizumab, 2397 patients had stroke or AMI. The risk of stroke (IRR=0.83, 95% CI 0.75 to 0.91) was not increased during the overall exposed period; however, there was a marginally elevated risk in ≥57 days exposed period (IRR=1.14, 95% CI 1.001 to 1.31). When analysing by the types of stroke, no increased risks of haemorrhagic (IRR=1.01, 95% CI 0.80 to 1.26) and ischaemic stroke (IRR=0.78, 95% CI 0.71 to 0.86) were observed during the exposed period, although the risks of ischaemic and haemorrhagic stroke were slightly elevated during ≥57 days exposed period. We could not find an association between ranibizumab and AMI. Conclusions Ranibizumab intravitreal injections did not increase the overall risk of stroke or AMI. Although the cardiovascular risk in patient receiving ranibizumab seems to be low, continuous monthly use of ranibizumab for high-risk patients should be judged carefully.