TY - JOUR
T1 - Sodium-Glucose Co-Transporter-2 Inhibitors and Cardiac Outcomes Among Patients Treated With Anthracyclines
AU - Gongora, Carlos A.
AU - Drobni, Zsofia D.
AU - Quinaglia Araujo Costa Silva, Thiago
AU - Zafar, Amna
AU - Gong, Jingyi
AU - Zlotoff, Daniel A.
AU - Gilman, Hannah K.
AU - Hartmann, Sarah E.
AU - Sama, Supraja
AU - Nikolaidou, Sofia
AU - Suero-Abreu, Giselle Alexandra
AU - Jacobsen, Eric
AU - Abramson, Jeremy S.
AU - Hochberg, Ephraim
AU - Barnes, Jeffrey
AU - Armand, Philippe
AU - Thavendiranathan, Paaladinesh
AU - Nohria, Anju
AU - Neilan, Tomas G.
N1 - Funding Information:
This work was supported by National Institutes of Health/National Heart, Lung, Blood Institute (T32HL076136 to Drs Gongora and Zafar; R01HL137562, R01HL130539, and K24HL150238 to Dr Neilan). Dr Drobni has received support from the New National Excellence Program of the Ministry for Innovation and Technology from the source of the National Research, Development, and Innovation Fund (ÚNKP-21-4-I-SE). Dr Zlotoff has received consulting fees from Bristol Myers Squibb and Freeline Therapeutics. Dr Armand has been a consultant for Merck, Bristol Myers Squibb, Pfizer, Affimed, Adaptive, Infinity, ADC Therapeutics, Celgene, Morphosys, Daiichi Sankyo, Miltenyi, Tessa, GenMab, C4, Enterome, Regeneron, Epizyme, AstraZeneca, and Genentech; and has received honoraria form Merk and Bristol Myers Squibb. Dr Thavendiranathan has received support from the Canadian Institutes of Health Research New Investigator Award (147814) and a Canada Research Chair in Cardio-oncology; and has received speaker fees from Amgen, Boehringer Ingelheim, and Takeda. Dr Neilan has served as the Michael and Kathryn Park Chair in Cardiology; has received support from A. Curtis Greer and Pamela Kohlberg, Christina and Paul Kazilionis, and a Hassenfeld Scholar Award; has been a consultant to and received fees from Parexel Imaging, Intrinsic Imaging, H3-Biomedicine, AbbVie, C4-Therapeutics, Roche, and Genentech, outside of the current work; has received consulting fees from Bristol Myers Squibb for a Scientific Advisory Board and consultancy focused on myocarditis related to immune checkpoint inhibitors; and has received grant funding from AstraZeneca and Bristol Myers Squibb. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
Publisher Copyright:
© 2022 American College of Cardiology Foundation
PY - 2022/8
Y1 - 2022/8
N2 - Background: Sodium-glucose co-transporter-2 (SGLT2) inhibitors improve outcomes among patients with established heart failure. Despite supportive basic science studies, there are no data on the value of SGLT2 inhibitors among patients treated with anthracyclines. Objectives: This study sought to test the cardiac efficacy and overall safety of SGLT2 inhibitors in patients treated with anthracyclines. Methods: This study identified 3,033 patients with diabetes mellitus (DM) and cancer who were treated with anthracyclines. Cases were patients with cancer and DM who were on SGLT2 inhibitor therapy during anthracycline treatment (n = 32). Control participants (n = 96) were patients with cancer and DM who were also treated with anthracyclines, but were not on an SGLT2 inhibitor. The primary cardiac outcome was a composite of cardiac events (heart failure incidence, heart failure admissions, new cardiomyopathy [>10% decline in ejection fraction to <53%], and clinically significant arrhythmias). The primary safety outcome was overall mortality. Results: Age, sex, ethnicity, cancer type, cancer stage, and other cardiac risk factors were similar between groups. There were 20 cardiac events over a median follow-up period of 1.5 years. The cardiac event incidence was lower among case patients in comparison to control participants (3% vs 20%; P = 0.025). Case patients also experienced lower overall mortality when compared with control participants (9% vs 43%; P < 0.001) and a lower composite of sepsis and neutropenic fever (16% vs 40%; P = 0.013). Conclusions: SGLT2 inhibitors were associated with lower rate of cardiac events among patients with cancer and DM who were treated with anthracyclines. Additionally, SGLT2 inhibitors appeared to be safe. These data support the conducting of a randomized clinical trial testing SGLT2 inhibitors in patients at high cardiac risk treated with anthracyclines.
AB - Background: Sodium-glucose co-transporter-2 (SGLT2) inhibitors improve outcomes among patients with established heart failure. Despite supportive basic science studies, there are no data on the value of SGLT2 inhibitors among patients treated with anthracyclines. Objectives: This study sought to test the cardiac efficacy and overall safety of SGLT2 inhibitors in patients treated with anthracyclines. Methods: This study identified 3,033 patients with diabetes mellitus (DM) and cancer who were treated with anthracyclines. Cases were patients with cancer and DM who were on SGLT2 inhibitor therapy during anthracycline treatment (n = 32). Control participants (n = 96) were patients with cancer and DM who were also treated with anthracyclines, but were not on an SGLT2 inhibitor. The primary cardiac outcome was a composite of cardiac events (heart failure incidence, heart failure admissions, new cardiomyopathy [>10% decline in ejection fraction to <53%], and clinically significant arrhythmias). The primary safety outcome was overall mortality. Results: Age, sex, ethnicity, cancer type, cancer stage, and other cardiac risk factors were similar between groups. There were 20 cardiac events over a median follow-up period of 1.5 years. The cardiac event incidence was lower among case patients in comparison to control participants (3% vs 20%; P = 0.025). Case patients also experienced lower overall mortality when compared with control participants (9% vs 43%; P < 0.001) and a lower composite of sepsis and neutropenic fever (16% vs 40%; P = 0.013). Conclusions: SGLT2 inhibitors were associated with lower rate of cardiac events among patients with cancer and DM who were treated with anthracyclines. Additionally, SGLT2 inhibitors appeared to be safe. These data support the conducting of a randomized clinical trial testing SGLT2 inhibitors in patients at high cardiac risk treated with anthracyclines.
KW - anthracycline-induced cardiomyopathy
KW - cardiotoxicity
KW - cardiovascular outcomes
KW - chemotherapy doxorubicin
KW - heart failure
KW - SGLT2 inhibitors
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U2 - 10.1016/j.jchf.2022.03.006
DO - 10.1016/j.jchf.2022.03.006
M3 - Article
C2 - 35902159
AN - SCOPUS:85134732643
VL - 10
SP - 559
EP - 567
JO - JACC: Heart Failure
JF - JACC: Heart Failure
SN - 2213-1779
IS - 8
ER -
