Dapagliflozin in heart failure: new frontiers

A Systematic Review and Network Meta-Analysis of Pharmacological Treatment of Heart Failure With Reduced Ejection Fraction

“…Results of trials published in the past year showed that treatment with sodium-glucose cotransporter 2 inhibitors (SGLT2i) empagliflozin (6) and dapagliflozin (7)(8)(9), soluble guanylase cyclase stimulator vericiguat (10), and cardiac-specific myosin activator omecamtiv-mecarbil (11) can further improve outcomes in HFrEF.…”

Sodium–glucose co‐transporter 2 inhibition in patients hospitalized for acute decompensated heart failure: rationale for and design of the EMPULSE trial

“…The potential modes of action of SGLT2 inhibition suggest their early use may be beneficial for patients with acute decompensated HF. SGLT2 inhibition improves myocardial energetics, and has direct positive effects on the cardiomyocyte and kidney 13,14,21–23 . In addition, empagliflozin might promote ketogenesis, which has a favourable effect on the heart and kidney by effectively increasing ‘fuel efficiency’ 14 .…”

“…SGLT2 inhibition improves myocardial energetics, and has direct positive effects on the cardiomyocyte and kidney. 13 , 14 , 21 , 22 , 23 In addition, empagliflozin might promote ketogenesis, which has a favourable effect on the heart and kidney by effectively increasing ‘fuel efficiency’. 14 SGLT2 inhibitors block reuptake of glucose and sodium in the proximal tubule, and can thus cause glucosuria‐mediated osmotic diuresis and possibly (at least transiently) natriuresis.…”

Anti-Diabetic Therapy, Heart Failure and Oxidative Stress: An Update

“…It was obvious that empagliflozin led to a significant reduction in the three-point composite primary outcome (CV death, non-fatal MI or non-fatal stroke) by 14% compared to placebo and a main reduction of about 38% in CV death ( p < 0.0001) within two months in the patients’ follow-up [ 39 , 75 , 76 ]. A secondary analysis of EMPA-REG OUTCOME strengthened the suggestion that empagliflozin was associated with a 35% reduction in hospitalization for HF ( p < 0.002), again quite early in the follow-up period after the therapy initiation, resulting in a positive effect on HF decompensation risk [ 77 , 115 , 126 ]. Overall mortality was also reduced by 32% ( p < 0.0001), a fact that seemed to be associated with a reduction in mortality associated with pump failure, while the arm of CV mortality related to atherosclerotic events presented no significant difference between the two subgroups [ 76 , 107 ].…”

“…The three SGLT-2 inhibitors (ipragliflozin, tofogliflozin and luseogliflozin) have only been approved in Japan [ 124 ]. There are four major cardiovascular outcome trials (CVOTs) about SGLT2 inhibitors: Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients Removing Excess Glucose (EMPA-REG OUTCOME) [ 125 , 126 , 127 , 128 ], the EMPRISE (empagliflozin comparative effectiveness and safety) [ 129 ], the impact of empagliflozin on cardiac function and biomarkers of heart failure in patients with acute myocardial infarction (EMMY) trial [ 130 ], the Empagliflozin Outcome Trial in Patients with Chronic Heart Failure with Preserved and Reduced Ejection Fraction (EMPEROR-PRESERVED [ 131 ] and EMPEROR-REDUCED [ 132 ]), EMPIRE-HF (Empagliflozin in heart failure patients with reduced ejection fraction) [ 133 ], the Canagliflozin Cardiovascular Assessment Study (CANVAS) Program [ 75 , 124 , 134 , 135 ], Comparative Effectiveness of Cardiovascular Outcomes in New Users of SGLT-2 Inhibitors (CVD-REAL) [ 121 ], the Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) trial [ 75 , 125 ] and Dapagliflozin Effect on Cardiovascular Events-Thrombolysis In Myocardial Infarction (DECLARE-TIMI 58) [ 75 , 136 , 137 , 138 ].…”