Empagliflozin improved CV outcomes in patients with HFrEF Empagliflozin significantly improved clinical outcomes vs placebo in patients with HFrEF with or without T2D in the EMPEROR-Reduced study1 Primary endpoint Secondary endpoints 30% RRR 25% RRR Reduced risk of first and recurrent HHF 5.2% ARR, NNT=19 Reduced risk of CV death or HHF Empagliflozin Cumulative incidence (%) 35 30 Placebo Significantly slowed decline in eGFR slope Empagliflozin vs placebo −2.28 −0.55 25 20 HR: 0.75 15 (95% CI: 0.65, 0.86) p<0.001 10 5 0 0 90 180 270 360 450 540 630 720 810 Days since randomization No. at risk Placebo 1867 1715 1612 1345 1108 854 611 410 224 109 Empa 1863 1763 1677 1424 1172 909 645 423 231 101 HR: 0.70 (95% CI: 0.58, 0.85) p<0.001 mL/min/1.73 m2/year p<0.001 View more safety data Overall safety data Similar rates of AEs and serious AEs in the empagliflozin and placebo treatment arms 76.2% Any AEs 41.4% Any serious AEs 78.5% 48.1% No clinically meaningful increases in hypovolaemia, 1,2 symptomatic hypotension, hyperkalaemia or UTIs Click-to-view inclusion criteria and study design Access full EMPEROR-Reduced paper here https://pubmed.ncbi.nlm.nih.gov/33197559/ In addition, empagliflozin reduced the risk of inpatient and outpatient worsening HF events* vs placebo3 Exploratory outcomes Empagliflozin reduced the severity of HF hospitalizations and the utilization of interventions, vs placebo Time to first Inpatient Outpatient 25% RRR 35% RRR 34% RRR 33% RRR HHF requiring IV vasopressor or positive inotropic drugs or mechanical or surgical intervention HHF that required intensive care emergency or urgent care visit for worsening HF requiring IV therapy study visit requiring intensification of diuretics HR: 0.65 (95% CI: 0.50, 0.85) p=0.002 HR: 0.66 (95% CI: 0.53, 0.83) p=0.0004 HR: 0.67 (95% CI: 0.58, 0.78) p<0.0001 HR: 0.75 (95% CI: 0.57, 0.98) p=0.03 12 DAYS Empagliflozin reduced the risk of a worsening HF event* with statistical significance reached at 12 days after randomization Improvements were seen across both inpatient and outpatient outcomes Access full clinical stability paper here https://pubmed.ncbi.nlm.nih.gov/33081531/ Patients treated with empagliflozin vs placebo showed benefits in terms of quality of life and NYHA functional class3,4 20–40% less likely to experience 20–40% more likely to experience Patients treated with empagliflozin vs placebo worsening NYHA class3 improvement in NYHA class3 Shifts in NYHA class were apparent at every scheduled assessment throughout the first year of follow-up Empagliflozin provided a significant early and sustained improvement in patients' quality of life based on KCCQ scores4 Conclusion Empagliflozin reduced the risk and total number of inpatient and outpatient worsening HF events as well as improved quality of life and NYHA functional class, vs placebo. Benefits were seen early and were sustained during follow-up. All hazard ratios (95% CI) are for empagliflozin vs placebo. *Worsening HF event defined as death, hospitalization for HF or an emergent or urgent HF visit requiring intravenous treatment. AE, adverse event; ARR, absolute risk reduction; CI, confidence interval; CV, cardiovascular; EF, ejection fraction; eGFR, estimated glomerular filtration rate; Empa, empagliflozin; GTI, genital tract infection; HF, heart failure; HFrEF, heart failure with reduced ejection fraction; HHF, hospitalization for heart failure; HR, hazard ratio; IV, intravenous; KCCQ, Kansas City Cardiomyopathy Questionnaire; LVEF, left ventricular ejection fraction; NNT, number needed to treat; NT-proBNP, N-terminal prohormone of brain natriuretic peptide; NYHA, New York Heart Association; OD, once daily; RRR, relative risk reduction; SOC, standard of care; T2D, Type 2 diabetes; UTI, urinary tract infection. This document provides a summary of key efficacy outcomes and related subanalyses from the EMPEROR-Reduced trial and is not intended to be a comprehensive reproduction. For full information, please refer to the original publications. 1. Packer M et al. N Engl J Med. 2020;383:1413; 2. Anker SD et al. Circulation 2021;143:337; 3. Packer M et al. Circulation 2021;143:326; 4. Butler J et al. Eur Heart J. 2021;42:1203. SC-CRP-08448 June 2021 Empagliflozin improved CV outcomes inPrimary patients with HFrEF endpoint Empagliflozin significantly improved clinical outcomes vs placebo in patients with HFrEF with or without T2D in the EMPEROR-Reduced study1 25% RRR 5.2% ARR, NNT=19 Secondary endpoints Reduced risk of CV death or HHF Significantly 30% RRR 25% RRR Cumulative incidence (%) Cumulative incidence (%) Primary endpoint 30Empagliflozin 35 30 slowed decline Reduced risk of first and Placebo recurrent HHF 5.2% ARR, NNT=19 35 Reduced risk of CVEmpagliflozin death or HHF in eGFR slope Empagliflozin vs placebo Placebo 20 HR: 0.75 20 15 10 (95% CI: 0.65, 0.86) p<0.001 15 5 HR: 0.75 (95% CI: 0.65, 0.86) p<0.001 0 0 No. at risk 90 10 180 270 360 450 540 630 720 810 Days since randomization Placebo 1867 1715 1612 1345 1108 854 611 410 224 109 Empa 1863 1763 1677 1424 1172 909 645 423 231 101 5 −2.28 −0.55 25 25 HR: 0.70 (95% CI: 0.58, 0.85) p<0.001 0 0 90 180 270 360 450 mL/min/1.73 m2/year p<0.001 540 630 720 Days since randomization No. at risk 1715 Overall safety data 1612 1345 1108 854 611 810 View more safety data Placebo 1867 410 224 Empa Similar 1863of AEs 1763 1677 AEs 1424 909 and 645placebo 423 treatment 231 arms 101 rates and serious in the1172 empagliflozin 76.2% 109 41.4% Any empagliflozin; serious AEs Any AEs ARR, absolute risk reduction; CI, confidence interval; CV, cardiovascular; Empa, HHF, hospitalization for heart failure; 78.5%risk reduction. Packer M et al. N Engl J Med. 2020;383:1413.48.1% HR, hazard ratio; NNT, number needed to treat; RRR, relative No clinically meaningful increases in hypovolaemia, 1,2 symptomatic hypotension, hyperkalaemia or UTIs Click-to-view inclusion criteria and study design Access full EMPEROR-Reduced paper here https://pubmed.ncbi.nlm.nih.gov/33197559/ Close Inclusion criteria No clinically meaningful increases in hypovolaemia, In addition, empagliflozin symptomatic hypotension, hyperkalaemiareduced or UTIs1,2 the risk of inpatient and outpatient worsening 10.6% 3 HF events* vs placebo Volume depletion 5.7% Symptomatic hypotension 5.5% reduced the severity of HF hospitalizations Empagliflozin and the utilization of interventions, vs placebo Empagliflozin (n=1863) 5.9% Hyperkalaemia events Placebo (n=1863) 6.8% Time to first Inpatient 4.9% Urinary tract infection (UTI) Genital tract infection (GTI) 9.9% Exploratory outcomes Outpatient Complicated 1.0% UTIs 0.8% 4.5% 1.7% 0.6% 25% RRR 0.3% Complicated GTIs 35% RRR 34% RRR 0.3% 33% RRR HHF requiring IV HHF that required or urgent study visit requiring No severe hypoglycaemia* inemergency patients without diabetes vasopressor or positive intensive care care visit for worsening 2intensification and no cases of ketoacidosis/diabetic ketoacidosis HR: 0.65 (95% CI: 0.50, 0.85) inotropic drugs or HF requiring IV therapy of diuretics p=0.002 HR: 0.66 (95% CI: 0.53, 0.83) HR: 0.67 (95% CI: 0.58, 0.78) mechanical or p=0.0004 p<0.0001 surgical intervention HR: 0.75 (95% CI: 0.57, 0.98) episode requiring assistance. *Defined as a hypoglycaemic p=0.03 1. Packer M et al. N Engl J Med. 2020;383:1413; 2. Anker SD et al. Circulation 2021;143:337. 12 DAYS Close Empagliflozin reduced the risk of a worsening HF event* with statistical significance criteriarandomization reached at 12Inclusion days after Improvements were seen across both • Ageand ≥18 years inpatient outpatient outcomes • Chronic HFrEF, NYHA II–IV • LVEF ≤40% • Receiving standard of care (SOC) Access full clinical stability paper here https://pubmed.ncbi.nlm.nih.gov/33081531/ No hospitalization required Ejection fraction (EF) ≥36% to ≤40% ≤40% ≥31% to ≤35% ≤30% Patients treated with empagliflozin vs placebo showed benefits in terms of quality of life and NYHA functional class3,4 and hospitalization for HF within 12 months 20–40% Without atrial fibrillation more likely With atrial fibrillation improvement less likely to experience worsening Patients treated with empagliflozin vs placebo NT-proBNP to experience 20–40% ≥600 ≥1200 pg/mL pg/mL ≥2500 ≥5000 pg/mL pg/mL NYHA class3 ≥1000 ≥2000 pg/mL pg/mL ≥600 ≥1200 pg/mL pg/mL in NYHA class3 Study design Shifts in NYHA class were apparent at every scheduled assessment throughout the first year of follow-up Empagliflozin 10 mg OD + SOC EMPEROR-Reduced LVEF ≤40% Placebo OD + SOC 3730 patients Median follow-up =16 months (event-driven) Empagliflozin provided a significant early HFrEF, heart failure with reduced ejection fraction; and LVEF, leftsustained ventricular ejection fraction; NT-proBNP, N-terminal prohormone of brain improvement in patients' natriuretic peptide; NYHA, New York Heart Association; OD, once daily; SOC, standard of care. Packer M et al. N Engl J Med. 2020;383:1413. quality of life based on KCCQ scores4 Conclusion Empagliflozin reduced the risk and total number of inpatient and outpatient worsening HF events as well as improved quality of life and NYHA functional class, vs placebo. Benefits were seen early and were sustained during follow-up. All hazard ratios (95% CI) are for empagliflozin vs placebo. *Worsening HF event defined as death, hospitalization for HF or an emergent or urgent HF visit requiring intravenous treatment. AE, adverse event; ARR, absolute risk reduction; CI, confidence interval; CV, cardiovascular; EF, ejection fraction; eGFR, estimated glomerular filtration rate; Empa, empagliflozin; GTI, genital tract infection; HF, heart failure; HFrEF, heart failure with reduced ejection fraction; HHF, hospitalization for heart failure; HR, hazard ratio; IV, intravenous; KCCQ, Kansas City Cardiomyopathy Questionnaire; LVEF, left ventricular ejection fraction; NNT, number needed to treat; NT-proBNP, N-terminal prohormone of brain natriuretic peptide; NYHA, New York Heart Association; OD, once daily; RRR, relative risk reduction; SOC, standard of care; T2D, Type 2 diabetes; UTI, urinary tract infection. This document provides a summary of key efficacy outcomes and related subanalyses from the EMPEROR-Reduced trial and is not intended to be a comprehensive reproduction. For full information, please refer to the original publications. 1. Packer M et al. N Engl J Med. 2020;383:1413; 2. Anker SD et al. Circulation 2021;143:337; 3. Packer M et al. Circulation 2021;143:326; 4. Butler J et al. Eur Heart J. 2021;42:1203. SC-CRP-08448 June 2021
