Bhandari M, Pradhan A, Vishwakarma P, Singh A, Sethi R. Sodium glucose cotransporter 2 inhibitors in the management of heart failure: Veni, Vidi, and Vici. World J Cardiol 2024; 16(10): 550-563 [PMID: 39492976 DOI: 10.4330/wjc.v16.i10.550]
Corresponding Author of This Article
Akshyaya Pradhan, FACC, FCCP, FESC, MBBS, MD, Professor, Department of Cardiology, King Georg’s Medical University, Shahmina Road, Chowk, Lucknow 226003, Uttar Pradesh, India. akshyaya33@gmail.com
Research Domain of This Article
Cardiac & Cardiovascular Systems
Article-Type of This Article
Minireviews
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Monika Bhandari, Akshyaya Pradhan, Pravesh Vishwakarma, Abhishek Singh, Rishi Sethi, Department of Cardiology, King Georg’s Medical University, Lucknow 226003, Uttar Pradesh, India
Author contributions: Bhandari M and Pradhan A conceived the project, performed the literature review, revised the manuscript based on the comments, and prepared the revised version; Vishwakarma P and Singh A wrote the draft manuscript; Sethi R critically reviewed the manuscript; Vishwakarma P made the figures; Singh A was responsible for the bibliography; Sethi R supervised the table construction; Pradhan A submitted the manuscript to the journal.
Conflict-of-interest statement: The authors have no conflicts of interest to declare.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Akshyaya Pradhan, FACC, FCCP, FESC, MBBS, MD, Professor, Department of Cardiology, King Georg’s Medical University, Shahmina Road, Chowk, Lucknow 226003, Uttar Pradesh, India. akshyaya33@gmail.com
Received: March 31, 2024 Revised: August 25, 2024 Accepted: September 6, 2024 Published online: October 26, 2024 Processing time: 200 Days and 5.7 Hours
Abstract
Heart failure (HF) is a chronic disease associated with high morbidity and mortality rates. Renin-angiotensin-aldosterone system blockers (including angiotensin receptor/neprilysin inhibitors), beta-blockers, and mineralocorticoid receptor blockers remain the mainstay of pharmacotherapy for HF with reduced ejection fraction (HFrEF). However, despite the use of guideline-directed medical therapy, the mortality from HFrEF remains high. HF with preserved ejection fraction (HFpEF) comprises approximately half of the total incident HF cases; however, unlike HFrEF, there are no proven therapies for this condition. Sodium glucose cotransporter-2 inhibitors (SGLT-2is) represent a new class of pharmacological agents approved for diabetes mellitus (DM) that inhibit SGLT-2 receptors in the kidney. A serendipitous finding from seminal trials of SGLT-2is in DM was the significant improvement in renal and cardiovascular (CV) outcomes. More importantly, the improvement in HF hospitalization (HHF) in the CV outcomes trials of SGLT-2is was striking. Multiple mechanisms have been proposed for the pleiotropic effects of SGLT-2is beyond their glycemic control. However, as patients with HF were not included in any of these trials, it can be considered as a primary intervention. Subsequently, two landmark studies of SGLT-2is in patients with HFrEF, namely, an empagliflozin outcome trial in patients with chronic HF and a reduced ejection fraction (EMPEROR-Reduced) and dapagliflozin and prevention of adverse outcomes in HF (DAPA-HF), demonstrated significant improvement in HHF and CV mortality regardless of the presence of DM. These impressive results pitchforked these drugs as class I indications in patients with HFrEF across major guidelines. Thereafter, empagliflozin outcome trial in patients with chronic HF with preserved ejection fraction (EMPEROR-Preserved) and dapagliflozin evaluation to improve the lives of patients with preserved ejection fraction HF (DELIVER) trials successively confirmed that SGLT-2is also benefit patients with HFpEF with or without DM. These results represent a watershed as they constitute the first clinically meaningful therapy for HFpEF in the past three decades of evolution of HF management. Emerging positive data for the use of SGLT-2is in acute HF and post-myocardial infarction scenarios have strengthened the pivotal role of these agents in the realm of HF. In a short span of time, these classes of drugs have captivated the entire scenario of HF.
Core Tip: Heart failure (HF) is associated with high morbidity and mortality rates. Sodium glucose cotransporter-2 inhibitors (SGLT-2is) are approved for diabetes mellitus (DM), and have also demonstrated improvement in renal and cardiovascular (CV) outcomes along with good glycemic control. Two landmark studies of SGLT-2is in patients with HF demonstrated improvement in HF hospitalization and CV mortality, irrespective of DM status. Subsequent clinical trials proved that SGLT-2is also benefit patients with HF with preserved ejection fraction with/without DM. Emerging positive data for SGLT-2is in acute HF and post-myocardial infarction scenarios have bolstered their pivotal role in the full diapason of HF.
