SGLT2 Inhibitors for Cancer Therapy-Related Cardiac Dysfunction
- SGLT2 inhibitor use for the treatment of cancer therapy–related cardiac dysfunction and heart failure (CTRCD/HF) has not been well studied.
- In this retrospective EHR database study, SGLT2 inhibitor use compared to no use among patients with CTRCD/HF was associated with less frequent HF exacerbations and all-cause mortality.
Among patients with cancer therapy–related cardiac dysfunction or heart failure (CTRCD/HF) on background HF therapies and type 2 diabetes mellitus (T2DM), what is the association between sodium-glucose cotransporter-2 (SGLT2) inhibitor use and clinical outcomes?
This retrospective cohort study used data from the TriNetX research network (electronic health record [EHR] data from 72 health care organizations with approximately 90 million patients) from January 2013 to April 2020. Included in the study were adult patients with a history of T2DM, prior cancer with exposure to potentially cardiotoxic cancer therapies, and a diagnosis of cardiomyopathy or HF following cancer therapy. Patients with a diagnosis of ischemic heart disease following cancer therapy were excluded. Among patients receiving background HF therapies (angiotensin receptor-neprilysin inhibitor/angiotensin-converting enzyme inhibitor/angiotensin-receptor blocker, beta-blocker, and mineralocorticoid receptor antagonist), patients prescribed an SGLT2 inhibitor were compared to those not on an SGLT2 inhibitor. The primary outcomes were HF exacerbations and all-cause mortality at 2 years. The secondary outcomes were all-cause hospitalizations or emergency room (ER) visits, atrial fibrillation and flutter, acute kidney injury, and need for renal replacement therapy.
A total of 6,988 patients with CTRCD/HF were identified. Of these, 654 patients were prescribed an SGLT2 inhibitor and 6,334 were not. After propensity score matching, 1,280 patients were included for analysis; 640 patients in each group. Baseline characteristics of the groups in the analysis cohort were similar.
For the primary outcomes, the patients with SGLT2 inhibitor therapy compared to those without were less likely to have an HF exacerbation (85 vs. 154 patients; odds ratio [OR], 0.483; 95% confidence interval [CI], 0.361-0.647; p = 0.001) and had lower all-cause mortality (73 vs. 194 deaths; OR, 0.296; 95% CI, 0.220-0.398; p < 0.001). For the secondary outcomes, SGLT2 inhibitor use compared to no use was also associated with less frequent all-cause hospitalizations or ER visits, atrial fibrillation and flutter, acute kidney injury, and renal replacement therapy. For safety outcomes, SGLT2 inhibitor use compared to no use was associated with less frequent urinary tract infections and similar frequency of lower extremity amputations.
Among patients with CTRCD/HF on background HF therapies and T2DM, SGLT2 inhibitor use compared to no use was associated with less frequent HF exacerbations and all-cause mortality.
Growing evidence has shown that SGLT2 inhibitor therapy has benefits for a wide range of disease states, including HF, T2DM, and chronic kidney disease. This study investigates whether the benefits seen in the HF population can be generalized to patients with CTRCD/HF. Prior work in preclinical models and smaller cohort studies have demonstrated a potential role for SGLT2 inhibitor therapy in this patient population. The results of this study support these findings and suggest that SGLT2 inhibitor use may have a cardioprotective effect in patients with CTRCD/HF.
The limitations of this study include the retrospective design, potential for incomplete or inaccurate data given the nature of the EHR database, lack of granular details on HF and cancer therapy regimens and disease course, the inclusion of only patients with T2DM, and unmeasured confounding variables. Future prospective studies would help to further define and confirm the role of SGLT2 inhibitor use in this population.
Keywords: Cancer, Heart Failure, Sodium-Glucose Transporter 2 Inhibitors
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