Sodium glucose cotransporter 2 inhibitors in the management of heart failure:Veni,Vidi,and Vici

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.