Abstract Body (Do not enter title and authors here): INTRODUCTION
Many anti-cancer agents, including alkylating, anthracycline-based, and anti-HER2 chemotherapies, have a high risk of causing clinically significant cardiac toxicity, manifesting as heart failure (HF). The efficacy of sodium-glucose cotransporter-2 inhibitors (SGLT2i's) in HFrEF and HFpEF is well-established; their role, however, in managing chemotherapy-related cardiac dysfunction (CTRCD) remains unclear.
AIMS
To analyze available data on the efficacy of SGLT2i's in CTRCD.
METHODS
Pubmed, Embase and Web of Science databases were queried to find relevant clinical studies on the use of SGLT2i's in CTRCD. Primary outcomes included HF incidence, HF exacerbations, and all-cause mortality. Using a random effects model, relative risk ratios (RRs) with 95% confidence intervals were computed for all outcomes.
RESULTS
Out of 807 retrieved citations, 4 observational studies with 6576 participants were included in the analysis. In SGLT2i's and non-SGLT2i's groups, the number of subjects, mean age, and proportion of males were 1551 vs. 5025, 67.6 vs. 68.9 years, and 42% (648) vs. 40% (2000) with median follow-up range of 1.5-3.4 years. Only one study enrolled patients with prior HF, while diabetes was common among all. Anthracyclines were the most common chemotherapy agents used and the majority of patients had a hematological malignany. Onset of HF in the SGLT2i's group, as reported by two studies, was 6/31 and 94/930 in the non-SGLT2is group. The pooled HF incidence rate was similar between the two groups, with an RR of 0.54 (0.25-1.16, p=0.11). SGLT2i's users had a significantly lower rate of HF exacerbations and all-cause mortality compared with those who did not receive SGLT2i's with RR of 0.54 (0.33-0.91, p=0.02) and 0.48 (0.32-0.73, p=0.0006), respectively. Additionally, SGLT2i's were associated with a significantly lower rate of arrhythmias [ RR 0.40 (0.22-0.70, p=0.001)]. The mortality effect was beleived to be influenced by the antitumor effects of SGLT2i's as well. Moreover, the rates of adverse events secondary to SGLT2i's, such as euglycemic ketoacidosis, hypoglycemia, and infections, were reported to be lower.
CONCLUSION
The observational data on the efficacy of SGLT2i's in CTRCD are promising. These drugs were found to have favorable effects on HF exacerbations, all-cause mortality, and arrhythmias onset associated with CTRCD. Large-scale randomized clinical trials are needed to validate these findings.