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Cardiovascular risk in patients receiving ranibizumab for exudative age-related macular degeneration: a nationwide self-controlled case-series study
  1. Ha-Lim Jeon1,
  2. Seong Jun Byun1,2,
  3. Nicole L Pratt3,
  4. Janet Sultana4,
  5. Sang Jun Park2,
  6. Ju-Young Shin1
  1. 1 School of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-do, South Korea
  2. 2 Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea
  3. 3 Quality Use of Medicines and Pharmacy Research Centre, Clinical and Health Sciences, University of South Australia, Adelaide, South Australia, Australia
  4. 4 Department of Biomedical and Dental Sciences and Morpho-functional Imaging, University of Messina, Messina, Sicily, Italy
  1. Correspondence to Dr Ju-Young Shin, School of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-do, South Korea; shin.jy{at}; Dr Sang Jun Park, Department of Ophthalmology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, South Korea; sangjunpark{at}


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.

  • degeneration
  • drugs
  • epidemiology
  • pharmacology
  • treatment medical

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  • SJP and J-YS contributed equally.

  • Contributors Study design: H-LJ, SJP and J-YS. Data collection and analysis: SJB and SJP. Interpretation: H-LJ, NLP, SJP and J-YS. Writing of the draft: H-LJ, NLP and JS. Critical revision of the draft: H-LJ, NLP, JS, SJP, and J-YS.

  • Funding This research was partially supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute funded by the Ministry of Health & Welfare, Republic of Korea (No. HI19C0373) and the national Research Foundation of Korea (NRF) grant funded by the Korea government (Ministry of Science and Information & Communication Technology, MSIT) (No. NRF-2020R1C1C1003527). NP was funded by Australian National Health and Medical Research Council Project Grant GNT1157506.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data may be obtained from a third party and are not publicly available. No data are available. Our study used the National Health Insurance database established by the National Health Insurance Service (NHIS) in South Korea. NHIS forbids transfer, rent or sale of the database to any other third party except the researchers who obtained the approval for the access to database (official website of NHIS:; contact number for data access: +82-33-736-2431).

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