Department of Medicine, Stony Brook University Medical Center, Stony Brook, New York, USA.
Am J Hypertens. 2010 May;23(5):460-8. doi: 10.1038/ajh.2010.25. Epub 2010 Feb 25.
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.
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.
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.
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.
高血压与贝伐单抗的使用有关，贝伐单抗是一种广泛用于癌症治疗的血管生成抑制剂。目前，尚不清楚与贝伐单抗相关的重度高血压的风险。我们进行了一项系统评价和荟萃分析，以评估接受贝伐单抗治疗的癌症患者发生重度高血压的风险。
从 PUBMED、Web of Science 和美国临床肿瘤学会会议摘要中检索了截至 2009 年 5 月的相关文献，以确定相关研究。合格的研究包括前瞻性随机对照临床试验，其中贝伐单抗直接与接受同时进行的抗肿瘤治疗的癌症患者的对照药物进行比较。采用固定或随机效应模型，根据纳入研究的异质性，计算汇总发病率、相对风险（RR）和 95%置信区间（CI）。
共有来自 20 项研究的 12656 例患有各种肿瘤的患者纳入分析。接受贝伐单抗治疗的患者发生所有级别高血压的发生率为 23.6%（95%CI：20.5-27.1），其中 7.9%（95%CI：6.1-10.2）为重度（3 或 4 级）。与对照组相比，接受贝伐单抗治疗的患者发生重度高血压的风险显著增加，RR 为 5.28（95%CI：4.15-6.71，P <0.001）。尽管没有统计学意义，但有趋势表明，贝伐单抗可能会增加高血压危象（4 级）的风险，RR 为 3.16（95%CI：0.91-10.90）。接受 2.5mg/kg/周（RR=4.78，95%CI：3.59-6.36）和 5mg/kg/周（RR=5.39，95%CI：3.68-7.90）贝伐单抗治疗的患者发生重度高血压的风险增加。重度高血压的风险可能因肿瘤类型而异，RR 范围从间皮瘤患者的 2.49（95%CI：0.94-6.59）到乳腺癌患者的 14.80（95%CI：0.92-238.51）。
贝伐单抗可能会显著增加癌症患者发生重度高血压的风险。强烈建议密切监测和充分管理，以降低心血管并发症的风险。
