Clinical Considerations for Use of SGLT2 Inhibitor Therapy in Patients with Heart Failure and Reduced Ejection Fraction: A Review

Abstract

Heart failure (HF) continues to increase in prevalence, representing a significant burden to healthcare systems in the USA. Despite several established HF therapies, particularly for HF with reduced ejection fraction (HFrEF), rates of HF hospitalizations and cardiovascular (CV) mortality remain very high. Type 2 diabetes (T2D) is an important risk factor for HF, with the two conditions often occurring concurrently. Several CV outcomes trials have shown that the sodium–glucose cotransporter 2 inhibitor (SGLT2i) class of antihyperglycemic drugs reduces the risk of HF-related outcomes in patients with T2D and either established CV disease or multiple CV risk factors. Subsequently, there have been large clinical studies that have investigated the effects of SGLT2is in patients with HFrEF, with or without T2D, which have shown that both dapagliflozin and empagliflozin have significant reductions in hospitalization for HF and CV mortality. These data led to US Food and Drug Administration approval of dapagliflozin and empagliflozin as a novel treatment pathway for patients with HFrEF; empagliflozin has subsequently been approved for the treatment of HF regardless of ejection fraction. A clinical practice algorithm can assist cardiologists in identifying patients who may be eligible for SGLT2i treatment as well as the appropriate timeframe for initiating therapy and the parameters for patient monitoring. Given the evidence that SGLT2is are beneficial in the management of HF, specifically HFrEF, irrespective of underlying T2D, evidence-based recommendations and greater clinician familiarity can facilitate the integration of SGLT2is into general HF therapeutic management.

Prescribing patterns of SGLT-2 inhibitors for patients with heart failure: A two-center analysis

“…Methods to integrate prescription of SGLT2i by physicians may include a clinical practice algorithm that considers each HF patient's unique risk factors and existing medications to help guide the selection of SGLT2i therapy [16] , [29] . The involvement of a well-coordinated team of healthcare providers, including cardiologists and primary care providers, will likely result in improved patient outcomes and increased satisfaction with care [1] .…”

Effect of dapagliflozin on the prognosis of patients with acute myocardial infarction undergoing percutaneous coronary intervention

“…Current treatment guidelines and expert consensus generally state that SGLT2i should be avoided whenever possible during acute progression, including in acute MI, to avoid hypovolemia, hypotension, ketoacidosis, or acute kidney injury. However, in clinical trials on acute and chronic HF, the risk of these adverse events in the SGLT2i treatment group was uncommon and not significantly higher than that in the placebo group [ 6 , 16 ]. Another safety concern during the perioperative management of patients with AMI is the repeated use of angiographic contrast agents during PCI, which may cause contrast-associated acute kidney injury.…”

New Directions in Pharmacological Treatment With SGLT-2 Inhibitor Molecules in the Light of Current Guidelines for Diabetes Mellitus, Heart Failure and Kidney Disease

“…In addition to their anti-diabetic effect, the use of SGLT-2 inhibitors has been associated with major cardio-protective mechanisms such as reduction of myocardial stretch and cardiac preload, modest reduction of inflammatory mediators, as well as increased production and myocardial utilization of ketone bodies, which may lead to decreased oxygen demand and improvement in cardiac function [11,17,32]. On the other hand, SGLT-2 inhibitors stabilize renal function by reducing the glomerular hyperfiltration in the early stages of diabetic kidney disease, probably as a result of vasoconstriction in the renal afferent arteriole and decreased post-glomerular vascular resistance [28,45,82]. Figure 1 summarizes the potential beneficial effects of SGLT-2 inhibition.…”