Predicting the Need for SGLT2 Inhibitors for Future Heart Failure

Diabetes is a well-known risk factor for the development of heart failure.¹ Pre-diabetes continues to grow in the United States.² This is important because pre-diabetes associated dysglycemia is associated with abnormal cardiac structure and function, associated with a higher risk of heart failure.^3-5 Over the last few years the sodium-glucose cotransporter-2 inhibitors (SGLT2i) reduce the risk of heart failure among patients with diabetes.⁶ Guidelines now recommend SGLT2i for high-risk cardiovascular disease event  (ASCVD) patients.^7-8 But most diabetic patients (≈75%) do not have established ASCVD. So how do with identify patients who might derive benefit from SGLT2i to prevent heart failure (HF)? 

A recent multicenter study enrolling the Atherosclerosis Risk in Communities (ARIC), Dallas Heart Study, and Multi-Ethnic Study of Atherosclerosis (MESA) studies 6799 participants (33.2% diabetes; 66.8% pre-diabetes showed that the 5-year risk for HF increased in a graded manner by using a cocktail of biomarkers.⁹ The biomarkers included high-sensitivity cardiac troponin-T ≥6 ng/L, N-terminal pro-B-type natriuretic peptide ≥125 pg/ml, high sensitivity C-reactive protein ≥3 mg/L, and left ventricular hypertrophy by electrocardiogram with 1 point for each abnormal biomarker. The highest risk was in ≥3 positive biomarkers (diabetes 12.0%), and pre-diabetes 7.8%).  The number of HF events prevented using SGLT2i per 1000 treated patients was 11 for all subjects (range: 4-44 0-≥3 positive biomarkers). Elevated levels of any of the biomarkers studies were independently associated with a higher risk of heart failure. 

The meaning of this data is that ordering any or all of these biomarkers gives clinicians a floor for predicting the benefits of SGLT2i for prevention of downstream heart failure, especially in patients without ASCVD. The SGLT2i are an expensive group of drugs in comparison to other goal-directed medical therapies for HFrEF. Perhaps this data might assist in formulary decisions and oversight use of these medications.

Mark A. Munger, PharmD, FCCP, FACC, is a professor of pharmacotherapy and adjunct professor of internal medicine, at the University of Utah, where he also serves as the associate dean of Academic Affairs for the College of Pharmacy.

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References:

1. Khan H, Anker SD, Januzzi JL Jr., et al. Heart failure epidemiology in patients with diabetes mellitus without coronary artery disease. J Card Fail 2019;25:78-86.
2. Centers for Disease Control and Prevention. National Diabetes Statistics Report. Available at: https://www.cdc.gov/diabetes/data/statistics/statistics-report.html. Accessed 02/04/2021
3. Rubin J, Matsushita K, Ballantyne CM, Hoogeveen R, Covesh J, Selvin E. Chronic hyperglycemia and subclinical myocardial injury. J Am Coll Cardiol 2012;59:484-9.
4. Skali H, Shah A, Gupta DK, et al. Cardiac structure and function across the glycemic spectrum in elderly men and women free of prevalent heart disease: the Atherosclerosis Risk in the Community study. Circ Heart Fail 2015;8:448-54.
5. Selvin E, Lazo M, Chen Y, et al. Diabetes mellitus, prediabetes, and evidence of subclinical myocardial damage. Circulation 2014;130:1374-82.
6. Zelnicker TA, Wiviott SD, Raz I, et al. SGLT2 inhibitors for primary and secondary prevention of cardiovascular and renal outcomes in type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcomes traits. Lancet 2019;393:31-9.
7. Das SR, Everett BM, Tircher KK, et al. 2018 ACC expert consensus decision pathway on novel therapies for cardiovascular risk reduction in patients with type 2 diabetes and atheroscleroritic cardiovascular disease: a report of the American College of Cardiology Task Force on expert consensus decision pathways. J Am Coll Cardiol 2018;72:3200-23.
8. American Diabetes Association. 10. Cardiovascular disease and risk management: standards of medical care in diabetes—2020.  Diabetes Care 2020;43:5111-34.
9. Pandey Am, Vaduganathan M, Patel KV, et al. Biomarker-based risk prediction of incident heart failure in pre-diabetes and diabetes. J Am Coll Cardiol Heart Failure 2021  https://doi.org/10.1016/j.jchf.2020.10.013