A systematic review and meta-analysis of cardioprotective effects of SGLT2 inhibitors compared to non-SGLT2 inhibitors in patients receiving cardiotoxic chemotherapy.

Abstract

e24037 Background: As anticancer therapies advanced over the past decades, cancer-related mortality has decreased, but the risk of cancer therapy-related cardiotoxicity has become an emerging concern in cancer survivors. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have shown protective effects against anthracycline (AC)-induced cardiotoxicity and exhibit partial anticancer effects in animal models. However, clinical evidence for this is scarce. We planned to study the cardioprotective effects of SGLT2 inhibitors in patients undergoing therapy with Cardiotoxic Chemotherapeutic agents. Methods: We conducted a systematic search of PubMed, Embase, and the Cochrane Library and identified Randomized Controlled Trials and observational studies comparing sodium-glucose cotransporter-2 inhibitors (SGLT2i) with non-SGLT2i therapy among cancer patients receiving Cardiotoxic chemotherapy. Outcomes included all-cause mortality, new-onset HF, heart failure (HF) exacerbation, HF hospitalization, myocardial infarction (MI), and arrhythmias. Dichotomous outcomes were pooled using a random-effects model in RevMan Version 5.4 to estimate risk ratios (RRs) with 95% confidence intervals (CIs). Heterogeneity was assessed using the I² statistic. Subgroup analyses were performed for anthracycline-based versus other potentially cardiotoxic chemotherapy regimens. Results: Six studies comprising 30,858 patients were included. SGLT2i therapy was associated with a significant reduction in all-cause mortality overall (RR = 0.54; 95% CI 0.41–0.70; P < 0.00001), with similar benefits in anthracycline-treated patients (RR = 0.48; 95% CI 0.28–0.83; P = 0.008) and in those receiving other cardiotoxic chemotherapy regimens (RR = 0.54; 95% CI 0.33–0.90; P = 0.02). HF hospitalization was significantly reduced with SGLT2i (RR = 0.31; 95% CI 0.18–0.55; P < 0.0001), as was the incidence of new-onset HF (RR = 0.28; 95% CI 0.10–0.82; P = 0.02), whereas HF exacerbation showed a nonsignificant trend toward reduction (RR = 0.60; 95% CI 0.28–1.29; P = 0.19). Arrhythmias were reduced by approximately 48% with SGLT2i therapy (RR = 0.52; 95% CI 0.32–0.85; P = 0.009), with no significant difference observed for MI (RR = 1.44; 95% CI 0.83–2.50; P = 0.20). Conclusions: This study shows a statistically significant reduction in all-cause mortality, heart failure incidence, hospitalizations, and cardiac supraventricular arrhythmias (Atrial fibrillation/flutter) in patients who received SGLT2 inhibitor therapy. Our analysis did not show any significant change in the incidence of Myocardial Infarction or frequency of heart failure exacerbations. This study also provides a foundation for future pharmacodynamic studies aimed at exploring the mechanisms underlying cardio-protection.