Impact of Renin-Angiotensin System Inhibitors On The Survival of Patients With Rectal Cancer

Abstract

Background Renin-angiotensin system inhibitors (RASIs) are widely used in the treatment of hypertension. However, their impact on the outcome of the combined treatment of rectal cancer is poorly understood. The aim of this study was to assess the effect of RASIs on the survival of rectal cancer patients with associated hypertension after neoadjuvant treatment and radical resection.Methods Between 2008 and 2016, 242 radical (R0) rectal resections for cancer were performed after neoadjuvant treatment in patients with associated hypertension. At the time of treatment, 158 patients were on RASIs, including 35 angiotensin-receptor antagonists (ARB) users and 123 angiotensin-converting enzyme inhibitors (ACEI) users. Eighty-four patients were on drugs other than RASIs (non-RASI users). The survival analysis was performed using the Kaplan-Meier estimator with the log-rank test and the Cox proportional hazards model.Results The log-rank test showed a significantly worse overall survival (OS) in the group of ACEI users compared to ARB users (p= 0.009) and non-RASI users (p= 0.013). As regards disease-free survival (DFS), worse survival was found in the ACEI group compared to ARB users and it was close to the statistical significance level (p= 0.064). The Multivariate Cox analysis showed a significant beneficial effect of ARBs on OS (HR: 0.326, 95% CI: 0.147-0.724, p= 0.006) and ARBs on DFS (HR: 0.339, 95% CI: 0.135-0.850, p= 0.021) compared to ACEIs. Other factors affecting OS included age (HR: 1.044, 95% CI: 1.016-1.073, p= 0.100), regional lymph node metastasis (ypN+) (HR: 2.157, 95% CI: 1.395-3.334, p= 0.001) and perineural invasion (PNI) (HR: 3.864, 95% CI: 1.799-8.301, p= 0.001). Additional factors affecting DFS included ypN+ (HR: 2.310, 95% CI: 1.374-3.883, p= 0.002) and PNI (HR: 4.351, 95% CI: 1.584-11.954, p= 0.004). Conclusions The use of ARBs instead of ACEIs may improve the outcome of the combined therapy for rectal cancer patients with associated hypertension.