SGLT2 inhibitors were associated with a 49-75% reduction in heart failure hospitalizations across observational studies of anthracycline-treated cancer patients, though likely inflated by confounding.
Does SGLT2i use prevent cancer therapy-related cardiac dysfunction and heart failure in anthracycline-treated cancer patients?
While observational data suggest SGLT2 inhibitors may protect against anthracycline-induced cardiotoxicity, the high likelihood of confounding biases means routine clinical use is not recommended until ongoing randomized trials are completed.
Randomized controlled trials (RCTs) evaluating the cardioprotective effects of sodium-glucose cotransporter-2 inhibitors (SGLT2i) on cancer therapy-related cardiac dysfunction (CTRCD) are scarce. This narrative review synthesizes the available evidence from six primary clinical studies (n=21,523), all of which are observational or non-randomized, and places these findings within their mechanistic and clinical context. Across studies, SGLT2i use is consistently associated with lower rates of cardiovascular events, including heart failure (HF) hospitalization and imaging-defined cardiac dysfunction. However, all estimates are subject to substantial residual confounding, including healthy user bias and immortal time bias, and should be considered hypothesis-generating rather than causal. The magnitude of observed associations exceeds what is mechanistically plausible based on established HF trials, further supporting the likelihood of bias. Current evidence therefore does not support routine clinical use of SGLT2i for CTRCD prevention. Three ongoing randomized trials will determine whether these observational signals translate into clinical benefit and define the role of SGLT2i in cardio-oncology practice.
Nabhan et al. (Tue,) conducted a review in Cancer therapy-related cardiac dysfunction (CTRCD) (n=21,523). Sodium-Glucose Cotransporter-2 Inhibitors (SGLT2i) vs. Unexposed controls not receiving SGLT2i was evaluated on Cancer therapy-related cardiac dysfunction and heart failure hospitalization. SGLT2 inhibitors were associated with a 49-75% reduction in heart failure hospitalizations across observational studies of anthracycline-treated cancer patients, though likely inflated by confounding.