Increased Risk of High-Grade Hypertension With Bevacizumab in Cancer Patients: A Meta-Analysis

BACKGROUND: Hypertension is associated with the use of bevacizumab, an angiogenesis inhibitor widely used in cancer therapy. Currently, the risk of severe hypertension associated with bevacizumab is unclear. We performed a systematic review and meta-analysis of published randomized-controlled clinical trials (RCTs) to assess the risk of high-grade hypertension in cancer patients treated with bevacizumab. METHODS: Databases from PUBMED, the Web of Science, and abstracts presented at the American Society of Clinical Oncology conferences until May 2009 were searched to identify relevant studies. Eligible studies included prospective RCTs in which bevacizumab was directly compared with controls in cancer patients receiving concurrent antineoplastic therapy. Summary incidence, relative risk (RR), and 95% confidence interval (CI) were calculated employing a fixed- or random-effects model based upon the heterogeneity of the included studies. RESULTS: A total of 12,656 patients with a variety of tumors from 20 studies were included for the analysis. The incidence of all-grade hypertension in patients receiving bevacizumab was 23.6% (95% CI: 20.5-27.1) with 7.9% (95% CI: 6.1-10.2) being high-grade (grade 3 or 4). Patients treated with bevacizumab had a significantly increased risk of developing high-grade hypertension with an RR of 5.28 (95% CI: 4.15-6.71, P < 0.001) in comparison with controls. Even though not statistically significant, there was a trend suggesting that bevacizumab may increase the risk of hypertensive crisis (grade 4) with an RR of 3.16 (95% CI: 0.91-10.90). The increased risk of high-grade hypertension was observed in patients receiving bevacizumab at 2.5 mg/kg/week (RR = 4.78, 95% CI: 3.59-6.36) as well as 5 mg/kg/week (RR = 5.39, 95% CI: 3.68-7.90). The risk of high-grade hypertension may vary with tumor types, with RRs ranging from 2.49 (95% CI: 0.94-6.59) in patients with mesothelioma to 14.80 (95% CI: 0.92-238.51) in patients with breast cancer. CONCLUSION: Bevacizumab may significantly increase the risk of high-grade hypertension in cancer patients. Close monitoring and adequate management are highly recommended to decrease cardiovascular complications.