Introduction: The cardiac adverse events (irAEs) secondary to immune checkpoint inhibitors (ICI) are associated with a high rate of morbidity and mortality. There are no data on the effect of concomitant sodium glucose cotransporter 2 inhibitors (SGLT2i) on the rates of major adverse cardiovascular events (MACE) among patients treated with an ICI. Hypothesis: Whether, the use of SGLT2i among ICI-treated patients may reduce MACE. Methods: This was a population-based cohort study between 2014 and 2023 including cancer patients treated with ICI aged over 18 years across the United States. SGLT2i use while on an ICI was defined as the initiation of SGLT2i therapy after the first record of ICI treatment among patients currently undergoing ICI therapy. The risk of incident MACE in patients on an ICI who were also prescribed an SGLT2i therapy was compared with 1:1 propensity score-matched patients on ICI who were never prescribed an SGLT2i. Hazard ratios (HRs) and 95% confidence intervals (CIs) for MACE were estimated using Cox proportional hazards regression. MACE was defined as a composite of myocardial infarction, heart failure (HF), and ischemic stroke. Results: There were 216 cancer patients undergoing ICI therapy who were newly treated with SGLT2i. These were compared to 216 controls. Over a mean follow-up period of six years, there were 107 MACE events. There were 44 events (20.4%) among those on an SGLT2i and 63 among controls (HR=0.61, 95% CI: 0.41-0.90; log-rank test p=0.011). Of the individual components of MACE, rates of HF were lower where there were 22 HF events (20.4%) among those on an SGLT2i and 37 among controls (HR=0.51, 95% CI: 0.30-0.86; log-rank test p=0.010). There were no differences in the rates of stroke (HR: 0.55, 95% CI: 0.29-1.04) and myocardial infarction (HR: 0.97, 95% CI: 0.38-2.43). Conclusions: In an observational, retrospective study, SGLT2i therapy was associated with a reduced risk for cardiac events compared to those who never treated with SGLT2i. These findings underscore the potential therapeutic value of SGLT2i in the prevention of MACE in cancer patients receiving immunotherapy and warrant further research.
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