Risk of regorafenib-induced cardiovascular events in patients with solid tumorsA systematic review and meta-analysis A systematic review and meta-analysis

Background: The present comparative meta-analysis was conducted to evaluate the cardiovascular events of regorafenib in patients with solid tumors. Methods: Eligible studies from MEDLINE, Google Scholar, Cochrane Library, Clinical key, EBSCO publishing and Ovid, which had reported cardiovascular adverse events potentially caused by regorafenib were absorbed. Data of clinical characteristics and cardiovascular events including hypertension, hemorrhage, thrombosis, and heart failure were extracted from selected literatures for the final analysis. Pooled analysis of cardiovascular adverse events was developed by relative risks (RRs) and corresponding 95% confidence intervals (CIs) with software STATA 13.0 and RevMan 5.3. Results: Thirty studies including 3813 patients were fit into analysis. The incidences of cardiovascular events of all-grade were: hypertension, 36.8% (95% CI, 29.8%-43.8%), hemorrhage, 8.6% (95% CI, 3.2%-14%), thrombosis, 1.4% (95% CI, 0.1%-2.8%), and heart failure, 2.9% (95% CI, 0.3%-5.6%). The incidences of cardiovascular events of high-grade were: hypertension, 9.9% (95% CI, 7.4%-12.4%), hemorrhage, 1.2% (95% CI, 0.3%-2.2%), thrombosis, 1.6% (95% CI, 0.2%-3.4%), and heart failure, 2.9% (95% CI, 0.3%-5.6%). The RRs and their 95% CIs of all-grade cardiovascular events among patients treated with regorafenib were: hypertension, 4.10 (95% CI, 3.07-5.46; P<.00001), hemorrhage, 2.71 (95% CI, 1.45-5.08; P=.002), thrombosis, 1.27 (95% CI, 0.49-3.27; P=.62), and heart failure, 0.79 (95% CI, 0.16-3.94; P=.77). The RRs and their 95% CIs of high-grade cardiovascular events among patients treated with regorafenib were: hypertension, 5.82 (95% CI, 3.46-9.78; P<.00001), hemorrhage, 0.90 (95% CI, 0.50-1.61; P=.72), thrombosis, 1.28 (95% CI, 0.48-3.41; P=.62), and heart failure, 1.15 (95% CI, 0.23-5.69; P=.86), respectively. Conclusion: The present meta-analysis has demonstrated that regorafenib is associated with an increasing risk of hypertension at all-grade and high-grade, as well as hemorrhage at all-grade. Adequate awareness of cardiovascular adverse events of regorafenib should be established for clinicians.