Meta-Analysis of Intraocular Bleeding With Dual Antiplatelet Therapy Using P2Y12 Inhibitors Prasugrel or Ticagrelor

Am J Cardiol. 2020 Apr 15;125(8):1280-1283. doi: 10.1016/j.amjcard.2020.01.012. Epub 2020 Jan 29.


Intraocular bleeding is a devastating clinical event due to its potentially blinding nature. It is not known if determine if dual antiplatelet therapy using aspirin and potent P2Y12 inhibitors increases this risk. We searched MEDLINE and for randomized controlled trials that were phase III, randomly assigned patients to dual antiplatelet therapy with either aspirin and a potent P2Y12 inhibitor or aspirin and clopidogrel, had follow-up of 6 months, and at least 200 patients. Corresponding authors were contacted for intraocular bleeding data. Inverse-variance, weighted, fixed-effects meta-analysis was undertaken, with random-effects meta-analysis performed as a sensitivity analysis. Four trials enrolling 42,850 patients were included. The median follow-up ranged from 12 to 14 months. There was overall low risk of bias. Pooled analysis demonstrated no statistically significant increase in the risk of intraocular bleeding with dual antiplatelet therapy using potent P2Y12 inhibitors compared with clopidogrel (risk ratio 0.89, 95% confidence interval 0.58 to 1.36). There was no significant heterogeneity observed across trials (I2 statistic 0%, p = 0.98). The use of random-effects meta-analysis did not change the effect estimate or confidence intervals, and the results appeared similar when stratified by potent P2Y12 inhibitor (p = 0.97). In conclusion, this collaborative meta-analysis of dual antiplatelet trials does not suggest that the risk of intraocular bleeding is increased with the use of potent P2Y12 inhibitors compared with clopidogrel. Our results suggest that these potent P2Y12 inhibitors may continue to be used cautiously where indicated as part of dual antiplatelet therapy, even in those at high risk of spontaneous intraocular bleeding.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Aspirin / therapeutic use*
  • Clinical Trials, Phase III as Topic
  • Clopidogrel / therapeutic use
  • Dual Anti-Platelet Therapy / methods
  • Eye Hemorrhage / chemically induced
  • Eye Hemorrhage / epidemiology*
  • Humans
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Prasugrel Hydrochloride / therapeutic use*
  • Purinergic P2Y Receptor Antagonists / therapeutic use*
  • Randomized Controlled Trials as Topic
  • Ticagrelor / therapeutic use*


  • Platelet Aggregation Inhibitors
  • Purinergic P2Y Receptor Antagonists
  • Clopidogrel
  • Prasugrel Hydrochloride
  • Ticagrelor
  • Aspirin