N-acetylcysteine therapy reduces major adverse cardiovascular events in patients with type 2 diabetes mellitus

Background: Effective preventive strategies for major adverse cardiovascular events (MACE) in T2DM patients are limited. Recent studies have explored the cardiovascular benefits of N-Acetylcysteine (NAC), an antioxidant with endothelial protective properties. This study investigates the long-term effects of NAC on MACE risk in T2DM patients, focusing on its potential as an adjunctive therapy. Methods: This population-based cohort study used data from Taiwan's National Health Insurance Research Database (NHIRD) and included 46,718 T2DM patients diagnosed between 2008 and 2018, with follow-up until December 31, 2021. Propensity score matching (PSM) ensured balanced comparisons between NAC users and non-users. Cox regression and time-dependent Cox hazards models assessed MACE risk, adjusting for multiple covariates. Results: In the matched cohort of 23,359 NAC users and 23,359 non-users, NAC users had a significantly lower incidence of MACE (41.74 % vs. 46.87 %, P < .0001). Adjusted Hazard Ratios (aHRs) indicated a consistent protective effect of NAC against overall MACE (aHR: 0.84; 95 % CI: 0.81-0.86, P < .0001). Higher cumulative defined daily doses (cDDD) of NAC correlated with reduced MACE risk, with the highest quartile (Q4) showing an aHR of 0.61 (95 % CI: 0.58-0.64, P < .0001). Conclusion: This study underscores the significant reduction in MACE risk among T2DM patients with long-term NAC therapy. Notably, the findings emphasize NAC's dose-dependent effectiveness in diminishing MACE incidence, indicating its potential as a valuable adjunctive therapy for managing cardiovascular risk in T2DM patients.