Impact of concomitant use of renin–angiotensin system inhibitors on survival in patients with pancreatic ductal adenocarcinoma: a systematic review and meta-analysis

Abstract

Background: Pancreatic ductal adenocarcinoma (PDAC) is characterized by poor prognosis and limited therapeutic options, particularly in the metastatic setting. Novel strategies to overcome treatment resistance are highly anticipated and may potentially include the repurposing of existing pharmacologic agents. Objectives: To prove the positive effect of angiotensin II receptor blockers (ARBs) or angiotensin-converting enzyme inhibitors (ACEIs) on survival in PDAC. Design: A systematic review and meta-analysis were conducted based on Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Data sources and methods: A systematic search of PubMed, Web of Science, and Cochrane databases was conducted to identify studies evaluating survival outcomes in patients with PDAC receiving concomitant treatment with ARBs or ACEIs. Survival outcomes were analyzed with random-effects models using hazard ratios (HRs) and 95% confidence intervals (CIs) extracted from included trials. Studies without sufficient survival data were reviewed qualitatively only. Results: A total of 14 studies, comprising a total of 19,287 patients, met the inclusion criteria. Results indicated that the concurrent treatment with ACEIs or ARBs in patients with PDAC was associated with significantly improved overall survival compared to no use (HR = 0.80; 95% CI: 0.76–0.86; p < 0.001). The survival benefit associated with the concomitant ACEI/ARB treatment was observed both in the curative setting (HR = 0.78, 95% CI 0.65–0.93, p = 0.007) and the non-curative setting (HR = 0.83, 95% CI 0.76–0.90, p < 0.001). Three studies without sufficient survival data for meta-analysis reported other potential benefits associated with the ACEI/ARB use. Conclusion: Our meta-analysis supports the efficacy of renin–angiotensin system inhibitors as concomitant therapy in patients with PDAC. Prospective randomized clinical trials are warranted to validate ACEI/ARB as adjunctive therapy in well-defined PDAC patient populations.