4.3 Time to onset of TKI associatied cardiovascular adverse event
The times of cardiac AEs occurrence were shown in Fig 3. Over 70% patients developed hypertension within 30 days after the first dose of TKIs treatment. Identical pattern were found in cardiac failure. However, the proportion of patients who developed cardiac failure within 30 days were higher in patients administered with sorafenib (70.31%) and regorafenib(75%), compared with lenvatinib (32.14%) and cabozantinib(46.15%). In the case of atrial fibrillation, most patients developed atrial fibrillation within 30 days after the first dose of sorafenib or regorafenib. We also found that the proportion of patients developed acute coronary syndrome increased after 180 days use of lenvatinib compared with the first 30 days(64.29% vs 28.57%). The proportion of patients developed acute myocardial infarction(AMI) within 30 days were higher in patients taking sorafenib(42.86%) when compared with lenvatinib(13.64%). On the contrary, lenvatinib seemed to induce cardiac AEs in a longer period, as the proportion of patients developed acute myocardial infarction were higher in patients taking lenvatinib(65.15%) when compared with sorafenib(20%) after 180 days administration.