Early initiation of SGLT2 inhibitors is important, irrespective of ejection fraction: SOLOIST‐WHF in perspective

The ultimate primary endpoint of SOLOST‐WHF—which in order to preserve statistical power was changed because of the premature closure of the study due to loss of funding from the sponsor during the onset of the COVID‐19 pandemic—was the composite of total HHF, urgent heart failure visits, or cardiovascular deaths The HR for the primary outcome was apparently similarly reduced in all groups (0 69, 0 74, and 0 66, respectively) Because the subgroup of patients with ejection fraction above 50% was modest in size, further data of SGLT2 inhibitors in heart failure with preserved ejection fraction (HFpEF) are eagerly anticipated 2 Figure DAPA‐HF, Study to Evaluate the Effect of Dapagliflozin on the Incidence of Worsening Heart Failure or Cardiovascular Death in Patients With Chronic Heart Failure;EF, ejection fraction;EMPEROR‐Reduced, EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Reduced Ejection Fraction;GDMT, guideline‐directed medical therapy;HFrEF, heart failure with a reduced ejection fraction;MRA, mineralocorticoid receptor antagonists;RASi, renin‐angiotensin system inhibitors;WHF, worsening heart failure The EMPEROR‐Preserved (EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Preserved Ejection Fraction) 34 and DELIVER (Dapagliflozin Evaluation to Improve the LIVEs of Patients With PReserved Ejection Fraction Heart Failure;ClinicalTrials gov Identifier: NCT03619213) trials that are ongoing will provide valuable information in those with HFpEF in the ambulatory setting

[1]  G. Filippatos,et al.  Effect of Empagliflozin on Cardiovascular and Kidney Outcomes in Patients with Heart Failure by Baseline Diabetes Status - Results from the EMPEROR-Reduced Trial , 2021, Diabetologie und Stoffwechsel.

[2]  J. Butler,et al.  Correction to: Effect of Empagliflozin on the Clinical Stability of Patients With Heart Failure and a Reduced Ejection Fraction: The EMPEROR-Reduced Trial. , 2021, Circulation.

[3]  P. Ponikowski,et al.  Empagliflozin and health-related quality of life outcomes in patients with heart failure with reduced ejection fraction: the EMPEROR-Reduced trial , 2021, European heart journal.

[4]  Deepak L. Bhatt,et al.  Sotagliflozin in Patients with Diabetes and Chronic Kidney Disease. , 2020, The New England journal of medicine.

[5]  Deepak L. Bhatt,et al.  Sotagliflozin in Patients with Diabetes and Recent Worsening Heart Failure. , 2020, The New England journal of medicine.

[6]  S. Verma,et al.  Effects of SGLT2 Inhibitors on Kidney and Cardiovascular Function. , 2020, Annual review of physiology.

[7]  Y. Jang,et al.  Randomized, Controlled Trial to Evaluate the Effect of Dapagliflozin on Left Ventricular Diastolic Function in Patients With Type 2 Diabetes Mellitus: The IDDIA Trial. , 2020, Circulation.

[8]  J. McMurray,et al.  Effect of Empagliflozin on Left Ventricular Volumes in Patients With Type 2 Diabetes, or Prediabetes, and Heart Failure With Reduced Ejection Fraction (SUGAR-DM-HF) , 2020, Circulation.

[9]  P. Ponikowski,et al.  Cardiac Myosin Activation with Omecamtiv Mecarbil in Systolic Heart Failure. , 2020, The New England journal of medicine.

[10]  P. Ponikowski,et al.  Ferric carboxymaltose for iron deficiency at discharge after acute heart failure: a multicentre, double-blind, randomised, controlled trial , 2020, The Lancet.

[11]  V. Fuster,et al.  Randomized Trial of Empagliflozin in Non-Diabetic Patients with Heart Failure and Reduced Ejection Fraction. , 2020, Journal of the American College of Cardiology.

[12]  P. Ponikowski,et al.  Effect of Empagliflozin on Cardiovascular and Renal Outcomes in Patients With Heart Failure by Baseline Diabetes Status , 2020, Circulation.

[13]  G. Filippatos,et al.  Cardiac and Kidney Benefits of Empagliflozin in Heart Failure Across the Spectrum of Kidney Function , 2020, Circulation.

[14]  Akshay S. Desai,et al.  Efficacy of Dapagliflozin on Renal Function and Outcomes in Patients With Heart Failure With Reduced Ejection Fraction , 2020, Circulation.

[15]  S. Verma,et al.  Two Tales: One Story. EMPEROR-Reduced and DAPA-HF. , 2020, Circulation.

[16]  Akshay S. Desai,et al.  Effect of Dapagliflozin on Outpatient Worsening of Patients With Heart Failure and Reduced Ejection Fraction , 2020, Circulation.

[17]  P. Ponikowski,et al.  Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure. , 2020, The New England journal of medicine.

[18]  D. DeMets,et al.  Effect of dapagliflozin according to baseline systolic blood pressure in the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure trial (DAPA-HF) , 2020, European heart journal.

[19]  D. DeMets,et al.  Dapagliflozin and Diuretic Use in Patients With Heart Failure and Reduced Ejection Fraction in DAPA-HF , 2020, Circulation.

[20]  M. Khan,et al.  Recognizing the Significance of Outpatient Worsening Heart Failure , 2020, Journal of the American Heart Association.

[21]  S. Verma,et al.  Mechanisms of Cardiovascular Benefits of Sodium Glucose Co-Transporter 2 (SGLT2) Inhibitors , 2020, JACC. Basic to translational science.

[22]  S. Solomon,et al.  Estimating lifetime benefits of comprehensive disease-modifying pharmacological therapies in patients with heart failure with reduced ejection fraction: a comparative analysis of three randomised controlled trials , 2020, The Lancet.

[23]  P. Ponikowski,et al.  Vericiguat in Patients with Heart Failure and Reduced Ejection Fraction. , 2020, The New England journal of medicine.

[24]  Akshay S. Desai,et al.  Effects of dapagliflozin in DAPA-HF according to background heart failure therapy , 2020, European heart journal.

[25]  Akshay S. Desai,et al.  Effect of Dapagliflozin on Worsening Heart Failure and Cardiovascular Death in Patients With Heart Failure With and Without Diabetes. , 2020, JAMA.

[26]  M. Packer SGLT2 Inhibitors Produce Cardiorenal Benefits by Promoting Adaptive Cellular Reprogramming to Induce a State of Fasting Mimicry: A Paradigm Shift in Understanding Their Mechanism of Action , 2020, Diabetes Care.

[27]  S. Verma Are the Cardiorenal Benefits of SGLT2 Inhibitors Due to Inhibition of the Sympathetic Nervous System?∗ , 2020, JACC. Basic to translational science.

[28]  H. Heerspink,et al.  Randomized, double‐blind, placebo‐controlled, multicentre pilot study on the effects of empagliflozin on clinical outcomes in patients with acute decompensated heart failure (EMPA‐RESPONSE‐AHF) , 2020, European journal of heart failure.

[29]  Deepak L. Bhatt,et al.  Effect of Empagliflozin on Left Ventricular Mass in Patients with Type 2 Diabetes and Coronary Artery Disease: The EMPA-HEART CardioLink-6 Randomized Clinical Trial. , 2019, Circulation.

[30]  D. DeMets,et al.  Effects of Dapagliflozin on Symptoms, Function, and Quality of Life in Patients With Heart Failure and Reduced Ejection Fraction , 2019, Circulation.

[31]  Lawrence A Leiter,et al.  Effect of Empagliflozin on Erythropoietin Levels, Iron Stores and Red Blood Cell Morphology in Patients with Type 2 Diabetes and Coronary Artery Disease. , 2019, Circulation.

[32]  Deepak L. Bhatt,et al.  The DAPA-HF Trial: A Momentous Victory in the War against Heart Failure. , 2019, Cell metabolism.

[33]  Deepak L. Bhatt,et al.  More CREDENCE for SGLT2 Inhibition. , 2019, Circulation.

[34]  G. Filippatos,et al.  Evaluation of the effects of sodium–glucose co‐transporter 2 inhibition with empagliflozin on morbidity and mortality in patients with chronic heart failure and a preserved ejection fraction: rationale for and design of the EMPEROR‐Preserved Trial , 2019, European journal of heart failure.

[35]  Christopher L. Roy,et al.  2019 ACC Expert Consensus Decision Pathway on Risk Assessment, Management, and Clinical Trajectory of Patients Hospitalized With Heart Failure: A Report of the American College of Cardiology Solution Set Oversight Committee. , 2019, Journal of the American College of Cardiology.

[36]  J. Butler,et al.  Timely Management of New-Onset Heart Failure. , 2019, Circulation.

[37]  S. Verma,et al.  Empagliflozin and Heart Failure. , 2019, Circulation.

[38]  G. Felker,et al.  Renal Effects of Intensive Volume Removal in Heart Failure Patients With Preexisting Worsening Renal Function. , 2019, Circulation. Heart failure.

[39]  J. McMurray,et al.  The Serendipitous Story of SGLT2 Inhibitors in Heart Failure. , 2019, Circulation.

[40]  S. Verma,et al.  A Big Win for Diabetic Kidney Disease: CREDENCE. , 2019, Cell metabolism.

[41]  Mahesh J. Patel,et al.  Clinical Course of Patients With Worsening Heart Failure With Reduced Ejection Fraction. , 2019, Journal of the American College of Cardiology.

[42]  P. Jüni,et al.  Pump, pipes, and filter: do SGLT2 inhibitors cover it all? , 2019, The Lancet.

[43]  M. Vaduganathan,et al.  Initiation, Continuation, Switching, and Withdrawal of Heart Failure Medical Therapies During Hospitalization. , 2019, JACC. Heart failure.

[44]  Deepak L. Bhatt,et al.  Can We DECLARE a Victory against Cardio-Renal Disease in Diabetes? , 2018, Cell metabolism.

[45]  S. Verma,et al.  Prevention of Heart Failure With SGLT-2 Inhibition: Insights From CVD-REAL. , 2018, Journal of the American College of Cardiology.

[46]  Roland A Matsouaka,et al.  Heart Failure With Preserved, Borderline, and Reduced Ejection Fraction: 5-Year Outcomes. , 2017, Journal of the American College of Cardiology.

[47]  A. Rudiger,et al.  Acute heart failure: from pathophysiology to optimal treatment , 2017 .

[48]  Gerasimos S Filippatos,et al.  2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. , 2017, Journal of the American College of Cardiology.

[49]  Gerasimos S Filippatos,et al.  2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. , 2017, Journal of cardiac failure.

[50]  S. Verma,et al.  Empagliflozin's Fuel Hypothesis: Not so Soon. , 2016, Cell metabolism.

[51]  Adrian F Hernandez,et al.  Trends in 30-Day Readmission Rates for Patients Hospitalized With Heart Failure: Findings From the Get With The Guidelines-Heart Failure Registry. , 2016, Circulation. Heart failure.

[52]  B. Charbonnel,et al.  Sotagliflozin as a potential treatment for type 2 diabetes mellitus , 2015, Expert opinion on investigational drugs.

[53]  Deepak L. Bhatt,et al.  Impact of Diabetes Mellitus on Hospitalization for Heart Failure, Cardiovascular Events, and Death: Outcomes at 4 Years From the Reduction of Atherothrombosis for Continued Health (REACH) Registry , 2015, Circulation.

[54]  M. Vaduganathan,et al.  The vulnerable phase after hospitalization for heart failure , 2015, Nature Reviews Cardiology.