e15131 Background: Immune checkpoint inhibitors (ICI) are associated with multiple immune related adverse events (irAE). Cardiotoxicities are rare but fatal complications. Since PD-1 and PD-L1 are expressed on human cardiomyocyte, there is an increased risk of cardiotoxicity with use of ICI. We performed a systematic review and meta-analysis to assess cardiotoxicities associated with PDL1 and CTLA4 inhibitors. Methods: The Embase, Ovid, Pubmed and Scopus were searched from inception to 2019 by two independent reviewers. All Phase II and III clinical trials reporting cardiotoxicities with the combination of, or monotherapy with anti-PD-1/PD-L1 and/or anti-CTLA4 were included. Our primary outcome was assessment of cardiotoxicity of all grades that included, hypertension, arrythmias, pericardial effusion, myocardial infarction, myocarditis, cardiomyopathy and cardiac arrest. Statistical heterogeneity was quantified using I2 statistics. The publication bias was assessed with Eggers regression test. The estimates were reported as odds Ratio (OR) with 95% confidence intervals (CI) using random effect model. Results: A total of 2,876 trials retrieved in the initial database search were analyzed according to PRISMA guidelines. Twenty trials met the inclusion criteria and were included in the final analysis. A total of 8,905 patients were included in these trials. There was no statistically significant difference in reported overall cardiotoxicity with ICI compared to placebo or standard of care (OR 0.953 95% CI 0.542-1.675, I2 89.49 p < 0.001). Also, no statistical significance associated with myocardial infarction (OR 0.76, 95% CI 0.76-3.298 I2 0%, P = 0.83), pericardial effusion (OR 1.44, 95% CI 0.72-2.90. I2= 0%, P = 0.613) or hypertension (OR 0.543, 95% CI 0.219-1.346. I2 = 94.98, P < 0.001). Myocarditis was reported in 8 patients with a statistically non-significant increased risk compared to standard of care or placebo (OR 2.16, 95% CI 0.719-6.828 I2= 0%, P = 0.885). Other reported cardiac irAE included cardiac arrest in 4 patients, QT prolongation in 2 patients and cardiac tamponade in 1 patient. Conclusions: The overall risk of cardiac related irAE is not significantly higher with ICI when compared with placebo or standard of care. The reported events of severe cardiac irAE like myocarditis and cardiac arrest are very low in the reported trials.
Antiarrhythmia drugs for cardiac arrest: a systemic review and meta-analysis
