Immune Checkpoint Inhibitors Do Not Increase Short-Term Risk of Hypertension in Cancer Patients: a Systematic Literature Review and Meta-Analysis
Shintaro Minegishi, Sho Kinguchi, Nobuyuki Horita, Ho Namkoong, Αlexandros Briasoulis, Tomoaki Ishigami, Kouichi Tamura, Akira Nishiyama, Yuichiro Yano, Japanese Society of Hypertension working group “Onco-Hypertension”
Abstract
Background: Immune checkpoint inhibitors (ICIs) are becoming widely used for novel cancer treatments. Immune-related adverse events, including cardiac toxicity, are frequently observed following immune checkpoint inhibitor (ICI) use. However, little is known regarding the association between ICIs initiation and hypertension in cancer patients. Methods: A systematic literature search was performed using PubMed, EMBASE, Cochrane Library, and Web of Science Core Collection. The risk of hypertension associated with ICI initiation in randomized controlled trials (RCTs) was evaluated. Hypertension was categorized according to the Common Terminology Criteria for Adverse Events. The odds ratios of grades I to V and grades III to V hypertension were calculated using a random-effects meta-analysis. Results: Thirty-two RCTs (n=19 810 cancer patients) were included. At a median follow-up of 36 months, the median overall survival was 15 months in the ICI group. ICI initiation was not significantly associated with hypertension (grades I–V: odds ratio, 1.12 [95% CI, 0.96–1.30]; grades III–V: odds ratio, 0.95 [95% CI, 0.78–1.16]). Additionally, no significant differences in hypertension risk were evident in ICI combination therapies with various drugs, including anti-VEGF (vascular endothelial growth factor) agents. In a subgroup analysis based on clinical setting (placebo RCT versus nonplacebo RCT), there were discrepancies between the results obtained with different methodologies, with patients in the nonplacebo RCTs having higher grades I–V hypertension (I 2 =88.6%, P for heterogeneity=0.003). Conclusions: ICI initiation was not associated with short-term risk of hypertension in cancer patients, and the association was similar regardless of concomitant treatment with other anticancer drugs.