Angiotensin-converting Enzyme Inhibitors Decrease the Incidence of Radiation-induced Pneumonitis Among Lung Cancer Patients: A Systematic Review and Meta-analysis

Background: Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) have been demonstrated to mitigate radiation-induced lung damage in animal models and preclinical studies. Our study aims to evaluate whether ACEIs or ARBs reduce the incidence of radiation-induced pneumonitis (RP) in lung cancer patients. Methods: Publications were searched from EMBASE, PubMed and Web of Science databases. Seven studies published from April 2000 to August 2016 met inclusion criteria and included 1412 patients in total. Only patients with grade 2 and above pneumonitis within 12 months after radiotherapy were analyzed. Results: Patients taking ACEIs had a lower risk of developing radiation pneumonitis compared with non-users (OR = 0.46, 95%CI = 0.31-0.67, p < 0.0001). While the use of ARBs couldn't reduce the incidence of RP (OR = 1.42, 95%CI = 0.94-2.14, p = 0.10). Elderly patients (age ≥ 70) benefited more from ACEIs (OR = 0.12, 95%CI = 0.02-0.67, p = 0.02). In addition, smokers were found to have a lower risk of developing RP than non-smokers (OR = 0.49, 95%CI = 0.30-0.81, p = 0.005), but sex and the use of statin or NSAID had no influence on the appearance of RP (p = 0.59, p = 0.70, p = 0.40, respectively). Conclusions: ACE inhibitors could decrease the incidence of symptomatic RP among lung cancer patients. However, the use of ARBs has a slight trend to develop RP but not above statistical significance. Elderly patients (age ≥ 70) benefited the most from ACEIs.