The impact of renin-angiotensin-aldosterone system inhibitors on immune checkpoint inhibitor-associated adverse cardiovascular events.

Abstract

2605 Background: Immune checkpoint inhibitors (ICIs) are associated with adverse cardiovascular events that impair patient outcomes. Previous observational studies showed that renin-angiotensin-aldosterone system inhibitors (RAASi) may mitigate the cardiotoxicity associated with chemotherapeutic agents. However, the effects of RAASi on ICI-associated adverse cardiovascular events are unknown. Methods: We conducted a 1:1 propensity score-matched cohort study involving ICI-treated patients at two tertiary referral centers in Taiwan. The propensity score matching model includes age, sex, hypertension, diabetes mellitus, chronic kidney disease, Eastern Cooperative Oncology Group (ECOG) Performance Scale, cancer stage, and cancer type. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of myocardial infarction (MI), ischemic stroke, peripheral arterial occlusive disease (PAOD), pulmonary embolism (PE), deep venous thrombosis (DVT), heart failure, pericardial disease, myocarditis, and cardiac arrhythmias. The secondary outcomes were arterial thrombotic events (MI, ischemic stroke, PAOD) and venous thrombotic events (PE and DVT). Results: We identified 684 patients eligible for inclusion, from which 164 patients who received RAASi were matched to patients who did not receive RAASi. Over a median follow-up of 9.1 months, the incidence rate of MACE for RAASi and non-RAASi recipients was 6.5 and 13.9 per 100 patient-years, respectively, resulting in an incidence rate ratio of 0.47 [95% CI: 0.21–1.00] (p = 0.038). In a multivariate Cox proportional hazard model adjusting for cancer therapy, RAASi recipients had an approximately 60% reduction in the risk for MACE (HR, 0.37 [95% CI: 0.16-0.86], p = 0.021). In the secondary analysis, RAASi were associated with a reduction in venous thrombotic events (HR, 0.11 [95% CI: 0.02-0.63], p = 0.013), but not for arterial thrombotic events (HR, 0.47 [95% CI: 0.06-3.38], p = 0.45). Conclusions: In patients receiving ICI therapy, the use of RAASi is associated with a decreased cardiovascular risk, particularly for venous thrombotic events. [Table: see text]