Supplementary Material for: Statin and Immune-Related Cardiovascular Events in Lung Cancer Patients Receiving Immune Checkpoint Inhibitors

Backgrounds: Immune checkpoint inhibitors (ICIs) have improved lung cancer treatment but are associated with an increased risk of cardiotoxicity. We investigated whether statins could mitigate ICI-associated cardiovascular risks in lung cancer patients.
Methods: We performed a retrospective, propensity score-matched cohort study utilizing the TriNetX database. We identified lung cancer patients receiving ICIs between April 2013 and June 2023. We created two cohorts: statin users and non-users. The primary efficacy outcome was major adverse cardiovascular events (MACE), defined as a composite of myocardial infarction, ischemic stroke, and heart failure. The secondary efficacy outcomes were myocarditis and cardiac arrest. Safety outcomes were all-cause mortality and serious immune-related adverse events (irAEs).
Results: A total of 16,650 lung cancer patients undergoing ICIs were identified, consisting of 6,812 statin users and 9,838 non-users. After propensity score matching, 4,379 patients were well-matched in baseline characteristics. Over a follow-up period of 12 months, statin use was associated with a lower risk of MACE (HR: 0.87, 95% CI: 0.78-0.98), primarily driven by reductions in myocardial infarction (HR: 0.75, 95% CI: 0.58-0.97) and heart failure (HR: 0.85, 95% CI: 0.74-0.98). For safety outcomes, statin use was associated with a reduction in all-cause mortality (HR: 0.83, 95% CI: 0.77-0.90) and did not result in an increased risk of serious irAEs.
Conclusions: The use of statins in lung cancer patients with cardiovascular risk factors and without previous cardiovascular events undergoing immunotherapy was associated with a reduction in MACE and all-cause mortality without an increased risk of serious adverse events.