Risk of liver dysfunction with ACE inhibitors based on real-world data from the MID-NET® in Japan.

Warnings about liver dysfunction in Japanese package inserts vary among angiotensin-converting enzyme (ACE) inhibitors, and risk assessment of liver dysfunction with ACE inhibitors has been limited. To evaluate the risk of liver dysfunction among patients prescribed ACE inhibitors available in Japan, we conducted this study based on the real-world data from MID-NET®. We identified patients who were newly prescribed ACE inhibitors between January 1, 2009 and December 31, 2019 and excluded patients with liver dysfunction before the first prescription of ACE inhibitors. To compare the risk of liver dysfunction between the control group (enalapril maleate) and each exposure group, a pairwise Cox proportional hazards model was employed to estimate the hazard ratio (HR) adjusted by inverse probability weighting based on the high-dimensional propensity score. A total of 29,817 patients were identified for analysis in the cohort. Compared with the control group, the HRs (95% confidence interval) were 1.37(0.79-2.38) for captopril, 0.71(0.33-1.54) for alacepril, 0.72(0.55-0.93) for imidapril hydrochloride, 1.08(0.86-1.34) for perindopril erbumine, and 0.69(0.52-0.91) for lisinopril hydrate. The risk of liver dysfunction with ACE inhibitors is unlikely to be a class-effect. Although continuous safety monitoring is necessary for promoting proper use of ACE inhibitors, the results indicate that no additional safety measures are currently required for ACE inhibitors that do not carry a liver dysfunction-related warning in Japan.