SGLT2 inhibitor empagliflozin prevents anthracycline-induced cardiotoxicity in a large-animal model
Abstract
While the development of cancer therapies has significantly improved the survival of cancer patients, more than 35% of cancer survivors treated with anthracyclines will develop cardiotoxicity. There is currently a lack of preventative therapies against anthracycline-induced cardiotoxicity (AIC). AIC is characterised by a disruption in myocardial metabolism. Sodium-glucose co-transporter (SLGT2) inhibitors represent a potential therapy as they have been shown to modulate myocardial substrate utilisation in other heart-failure contexts.
We developed a highly translational large-animal model to test the ability of SGLT2 inhibitor empagliflozin to prevent AIC at different doses.
Female Large-White pigs were randomised (2:1:1) to no treatment (AIC-control group) or empagliflozin at a daily oral dose of 10 mg or 20 mg, beginning at the start of the doxorubicin regimen and continuing to 21 weeks. All pigs received 6 doses of doxorubicin intravenous infusion (25 mg/m2/every 3 weeks) with 2 additional off-dose visits. Pigs were assessed by cardiac magnetic resonance (CMR) and MR spectroscopy (MRS) at baseline and every 3 weeks for 21 weeks. At the end of 21-week follow-up, the LV was collected and processed for analysis by transmission electron microscopy (TEM) and mitochondrial respirometry.
The primary outcome, final LVEF, was significantly higher in pigs receiving 20 mg empagliflozin than in the AIC-control group (57.5% (IQR=55.5, 60.3) vs 47.0% (40.8, 47.8); p=0.027). Final LVEF…
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Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design.
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