Angiotensin converting enzyme inhibitor and angiotensin receptor blocker use and outcomes in patients with colorectal cancer.

Abstract

544 Background: Increasing evidence implicates angiotensin in the pathophysiology of carcinogenesis. Both Angiotensin Converting Enzyme Inhibitors (ACEIs) and Angiotensin Receptor Blockers (ARBs) have shown in-vitro activity in Colorectal Cancer (CRC) via inhibition of both VEGF and IGF-1 and present a novel therapeutic strategy. This study aimed to investigate the association of these agents in outcomes of patients with CRC. Methods: We reviewed the medical records of patients with stage I-III CRC from 2004-2008. ACEI and ARB use was defined as consumption for at least 3 months in patients with no evidence of disease after initial diagnosis and treatment. Outcomes were Disease Free Survival (DFS) and Overall Survival (OS). Kaplan-Meier and Cox proportional hazards regression were used. Results: A total of 222 patients were included, with a median follow up of 39 months. A total of 105 (47%) were identified as users of ACEI/ARBs. Multivariate analysis, adjusted to age, sex, race, stage, grade, tumor location, adjuvant chemotherapy, radiotherapy, statin and ASA use showed significantly improved DFS among users of ACEI and/or ARBs compared to non-users (HR = 0.44, p = 0.003). Considered separately, users of ACEIs only and users of ARBs only had better DFS than non-users (HR = 0.43 and 0.53, respectively). Compared directly, users of ACEIs did not have significantly different DFS than users of ARBs (HR = 0.81, p = 0.678). With regards to OS, multivariate analysis showed that, compared to non-users, patients with ACEI or ARB use had better OS, although non-significantly (HR = 0.59, p = 0.219). However, the magnitude of the impact on OS was comparable to that seen for DFS. Conclusions: The use of ACEIs and/or ARBs is associated with improved disease-free survival in CRC patients. There was a statistically insignificant trend toward improved OS, which may be related to the low power to the study. This observation warrants further exploration.