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Meta-Analysis
. 2018 Oct;97(41):e12705.
doi: 10.1097/MD.0000000000012705.

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

Jianxin Chen  1 , Junhui Wang  2
Affiliations
Meta-Analysis

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

Jianxin Chen et al. Medicine (Baltimore). 2018 Oct.

Abstract

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.

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Conflict of interest statement

Authors declare that they have no conflicts of interest.

Figures

Figure 1
Figure 1
Study selection procedure with PRISMA flow diagram. PRISMA = Preferred Reporting Items for Systematic Reviews and Meta-Analyses.
Figure 2
Figure 2
Risk of bias summary: review authors’ judgments about each risk of bias item for each included study.
Figure 3
Figure 3
Risk of bias graph: review authors’ judgments about each risk of bias item presented as percentages among all included studies.
Figure 4
Figure 4
(A–D). Forest plots of relative risk of cardiovascular events of all-grade associated with regorafenib versus control. A. Hypertension; B. Hemorrhage; C. Thrombosis; D. Heart failure.
Figure 5
Figure 5
(A–D). Forest plots of relative risk of cardiovascular events of high-grade associated with regorafenib versus control. A. Hypertension; B. Hemorrhage; C. Thrombosis; D. Heart failure.
See this image and copyright information in PMC

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