http://manuscript.elsevier.com/S0140673622003695/pdf/S0140673622003695.pdf

Reduction of dietary sodium to less than 100 mmol in heart failure (SODIUM-HF): an international, open-label, randomised, controlled trial

Sodium-glucose co-transporter 2 (SGLT2) inhibitors have been recently recommended as a foundational therapy for patients with heart failure (HF) and reduced ejection fraction (HFrEF) because of their favourable effects on mortality, clinical events and quality of life. While clinical practice guidelines have recommended the use of dapagliflozin and empagliflozin regardless of diabetes history in patients with HFrEF, or sotagliflozin in those with HFrEF and concomitant type 2 diabetes mellitus (T2DM), the timing and practical integration of this class of therapies in practice is less well defined. We propose that these drugs are candidates for early, upfront administration to patients with newly diagnosed HFrEF and for patients hospitalized with HF. Growing evidence has established early benefits, with clinically meaningful reductions in clinical events that reach statistical significance within days to weeks, following dapagliflozin, empagliflozin or, in diabetic patients, sotagliflozin initiation. Secondly, although major clinical trials have tested these drugs in patients already receiving background HF therapy, secondary analyses showed that their efficacy is independent of that. Third, SGLT2 inhibitors are generally safe and well tolerated, with clinical trial data reporting minimal effects on blood pressure, glycaemia-related adverse events, and no excess in acute kidney injury. Rather, they exert renal protective effects and reduce risk of hyperkalaemia, properties that favour initiation, tolerance and persistence of renin-angiotensin-system inhibitors and mineralocorticoid receptor antagonists. This review, therefore, supports the early initiation of dapagliflozin and empagliflozin (or sotagliflozin limited to patients with T2DM) to rapidly improve clinical outcome and quality of life of HFrEF patients. This article is protected by copyright. All rights reserved. 

/pdf/sodium-glucose-co-transporter-2-inhibitors-as-an-early-first-g59arvsb.pdf

Sodium–glucose co‐transporter 2 inhibitors as an early, first‐line therapy in patients with heart failure and reduced ejection fraction

https://doi.org/10.1016/j.jacbts.2021.10.018

Optimizing Foundational Therapies in Patients With HFrEF

A Novel Approach to Medical Management of Heart Failure With Reduced Ejection Fraction.

Type 2 diabetes (T2D) is one of the most common causes of chronic kidney disease (CKD) and cardiovascular (CV) disease. Until recently, glycemic and BP control were the cornerstones for preventing progression of CKD and CV disease associated with T2D. However, there has been a paradigm shift in treatment since the publication of the first clinical trial demonstrating benefits of sodium glucose cotransporter 2 (SGLT2) inhibitors in 2015. SGLT2 inhibitors have been shown to reduce the risk of major adverse CV events and progression of kidney disease in the setting of T2D. However, the elucidation of mechanisms of underlying these clinical benefits is the subject of ongoing investigation. Experimental studies have shown that SGLT2 inhibitors have diverse pleiotropic effects such as modulation of neurohormones such as the renin-angiotensin-aldosterone system, increasing hematocrit, altering energy substrate use, and attenuating systemic inflammation and oxidative stress, all of which have been implicated in the CV and kidney protective effects of SGLT2 inhibitors. In this review, we highlight biomarkers linked with diabetic kidney disease and heart failure and discuss how SGLT2 inhibitor-associated changes potentially mediate the cardiorenal protection observed with these therapies.

Cardiorenal protection with SGLT2 inhibitors in patients with diabetes mellitus: from biomarkers to clinical outcomes in heart failure and diabetic kidney disease.

Jodi Heshka

Papers

CCS/CHFS Heart Failure Guidelines Update: Defining a New Pharmacologic Standard of Care for Heart Failure With Reduced Ejection Fraction