2024
Effects of dapagliflozin in heart failure according to duration of type 2 diabetes: a patient-level meta-analysis of DAPA-HF and DELIVER
Butt J, De Boer R, Hernandez A, Inzucchi S, Kosiborod M, Koeber L, Lam C, Martinez F, Ponikowski P, Sabatine M, Shah S, Vaduganathan M, Jhund P, Solomon S, Mcmurray J. Effects of dapagliflozin in heart failure according to duration of type 2 diabetes: a patient-level meta-analysis of DAPA-HF and DELIVER. European Heart Journal 2024, 45: ehae666.1097. DOI: 10.1093/eurheartj/ehae666.1097.Peer-Reviewed Original ResearchEffects of dapagliflozinT2D durationHeart failureEjection fractionPrimary outcomeDAPA-HFCardiovascular deathNew York Heart Association functional classPro-B-type natriuretic peptide levelsN-terminal pro-B-type natriuretic peptide levelsComposite of worsening HFLeft ventricular ejection fractionPatient-level pooled analysisRisk of worsening HFAssociated with worse outcomesDuration of type 2 diabetesSafety of dapagliflozinPatient-level meta-analysisBenefits of dapagliflozinNatriuretic peptide levelsVentricular ejection fractionReduced ejection fractionHistory of T2DDuration of HFDuration of T2DEffect of dapagliflozin in patients with diabetes and heart failure with mildly reduced or preserved ejection fraction according to background glucose‐lowering therapy: A pre‐specified analysis of the DELIVER trial
Lassen M, Ostrominski J, Inzucchi S, Claggett B, Kulac I, Jhund P, de Boer R, Hernandez A, Kosiborod M, Lam C, Martinez F, Shah S, Desai A, Petersson M, Langkilde A, Docherty K, McMurray J, Solomon S, Vaduganathan M. Effect of dapagliflozin in patients with diabetes and heart failure with mildly reduced or preserved ejection fraction according to background glucose‐lowering therapy: A pre‐specified analysis of the DELIVER trial. European Journal Of Heart Failure 2024, 26: 1539-1548. PMID: 38745498, DOI: 10.1002/ejhf.3269.Peer-Reviewed Original ResearchConceptsBackground glucose-lowering therapyLeft ventricular ejection fractionGlucose-lowering therapySodium-glucose cotransporter 2 inhibitorsHeart failureClinical outcomesComposite of worsening HFPrimary outcomeInsulin useBenefits of dapagliflozinVentricular ejection fractionEffects of dapagliflozinType 2 diabetesEjection fractionRandomized patientsMetformin useConcomitant metforminCardiovascular deathFollow-upContemporary guidelinesDapagliflozinTreatment effectsDELIVER trialTreatment benefitT2DPrognostic Models for Mortality and Morbidity in Heart Failure With Preserved Ejection Fraction
McDowell K, Kondo T, Talebi A, Teh K, Bachus E, de Boer R, Campbell R, Claggett B, Desai A, Docherty K, Hernandez A, Inzucchi S, Kosiborod M, Lam C, Martinez F, Simpson J, Vaduganathan M, Jhund P, Solomon S, McMurray J. Prognostic Models for Mortality and Morbidity in Heart Failure With Preserved Ejection Fraction. JAMA Cardiology 2024, 9: 457-465. PMID: 38536153, PMCID: PMC10974691, DOI: 10.1001/jamacardio.2024.0284.Peer-Reviewed Original ResearchConceptsNT-proBNP levelsHF hospitalizationHeart failureCardiovascular deathNT-proBNPPARAGON-HFClinical outcomesN-terminal pro-brain natriuretic peptideAngiotensin receptor-neprilysin inhibitionComposite of HF hospitalizationSodium-glucose cotransporter 2 inhibitorsHigh-sensitivity cardiac troponin TMeta-Analysis Global GroupPro-brain natriuretic peptidePARAGON-HF trialBiomarker-driven approachesRisk of cardiovascular deathHigh-risk patientsInformed care decisionsCardiac troponin TPredictive of all-causePredictive of morbidityTransient ischemic attack/strokeChronic obstructive pulmonary diseaseObstructive pulmonary diseaseDapagliflozin and Timing of Prior Heart Failure Hospitalization A Patient-Level Meta-Analysis of DAPA-HF and DELIVER
Butt J, Jhund P, Docherty K, Claggett B, Vaduganathan M, Bachus E, Hernandez A, Lam C, Inzucchi S, Martinez F, de Boer R, Kosiborod M, Desai A, Køber L, Ponikowski P, Sabatine M, Solomon S, McMurray J. Dapagliflozin and Timing of Prior Heart Failure Hospitalization A Patient-Level Meta-Analysis of DAPA-HF and DELIVER. JACC Heart Failure 2024, 12: 1586-1599. PMID: 38573262, DOI: 10.1016/j.jchf.2024.01.018.Peer-Reviewed Original ResearchConceptsHF hospitalizationDAPA-HFHeart failureComposite of worsening HFPrimary outcomePatient-level pooled analysisRisk of adverse clinical outcomesBenefits of dapagliflozinMedian follow-upMonths of randomizationEffects of dapagliflozinAdverse clinical outcomesPrior HF hospitalizationHospital categoryPrimary endpointPrevent 1 eventClinical outcomesAbsolute benefitEffective therapyFollow-upCardiovascular deathDapagliflozinAssociated with timeHigh riskPatientsDapagliflozin and Days of Full Health Lost in the DAPA-HF Trial
Kondo T, Mogensen U, Talebi A, Gasparyan S, Campbell R, Docherty K, de Boer R, Inzucchi S, Køber L, Kosiborod M, Martinez F, Sabatine M, Bengtsson O, Sjöstrand M, Vaduganathan M, Solomon S, Jhund P, McMurray J. Dapagliflozin and Days of Full Health Lost in the DAPA-HF Trial. Journal Of The American College Of Cardiology 2024, 83: 1973-1986. PMID: 38537918, DOI: 10.1016/j.jacc.2024.03.385.Peer-Reviewed Original ResearchConceptsDAPA-HFLeft ventricular ejection fractionNYHA functional class IIEfficacy of dapagliflozinFunctional class IIIV heart failureVentricular ejection fractionEffects of dapagliflozinHeart failure hospitalizationDAPA-HF trialWell-beingFollow-up daysBetween-treatment differencesDapagliflozin groupPlacebo groupTime-to-first-event analysisEjection fractionFailure hospitalizationPatient well-beingHeart failureCardiovascular deathDapagliflozinRecurrent hospitalizationsClass IIPlaceboDapagliflozin in patients with heart failure and previous myocardial infarction: A participant‐level pooled analysis of DAPA‐HF and DELIVER
Peikert A, Vaduganathan M, Claggett B, Kulac I, Foà A, Desai A, Jhund P, Carberry J, Lam C, Kosiborod M, Inzucchi S, Martinez F, de Boer R, Hernandez A, Shah S, Køber L, Ponikowski P, Sabatine M, Petersson M, Langkilde A, McMurray J, Solomon S. Dapagliflozin in patients with heart failure and previous myocardial infarction: A participant‐level pooled analysis of DAPA‐HF and DELIVER. European Journal Of Heart Failure 2024, 26: 912-924. PMID: 38487939, DOI: 10.1002/ejhf.3184.Peer-Reviewed Original ResearchConceptsLeft ventricular ejection fractionHeart failureHistory of MIMyocardial infarctionPrimary outcomeDAPA-HFWorsening HFSpectrum of left ventricular ejection fractionLeft ventricular ejection fraction spectrumCardiovascular deathSodium-glucose cotransporter 2 inhibitorsRisk of disease progressionComposite of cardiovascular deathRisk of adverse cardiovascular outcomesIncreased risk of adverse cardiovascular outcomesRisk of cardiovascular deathVentricular ejection fractionHistory of myocardial infarctionSerious adverse eventsAdverse cardiovascular outcomesSymptomatic HFEjection fractionAdverse eventsCovariate-adjusted modelsPooled analysisDapagliflozin and Mode of Death in Heart Failure With Improved Ejection Fraction
Vardeny O, Desai A, Jhund P, Fang J, Claggett B, de Boer R, Hernandez A, Inzucchi S, Kosiborod M, Lam C, Martinez F, Shah S, Mc Causland F, Petrie M, Vaduganathan M, McMurray J, Solomon S. Dapagliflozin and Mode of Death in Heart Failure With Improved Ejection Fraction. JAMA Cardiology 2024, 9: 283-289. PMID: 38265835, PMCID: PMC10809142, DOI: 10.1001/jamacardio.2023.5318.Peer-Reviewed Original ResearchConceptsLeft ventricular ejection fractionMode of deathEjection fractionCause-specific deathHeart failureCardiovascular deathNew York Heart Association class IIGuideline-directed medical therapyStudy case report formsSudden deathVentricular ejection fractionRate of sudden deathAssociated with lower ratesCox regression modelsImproved ejection fractionRandomized clinical trialsReduce cardiovascular mortalityCase report formsEnd-point committeeClinical end point committeePost hoc analysisDapagliflozin EvaluationIV symptomsHFimpEFMedical therapy
2023
Effects of dapagliflozin in heart failure with preserved ejection fraction and chronic obstructive pulmonary disease: an analysis of the DELIVER trial
Butt J, Lu H, Kondo T, Bachus E, De Boer R, Hernandez A, Inzucchi S, Jhund P, Kosiborod M, Lam C, Martinez F, Shah S, Vaduganathan M, Solomon S, Mcmurray J. Effects of dapagliflozin in heart failure with preserved ejection fraction and chronic obstructive pulmonary disease: an analysis of the DELIVER trial. European Heart Journal 2023, 44: ehad655.949. DOI: 10.1093/eurheartj/ehad655.949.Peer-Reviewed Original ResearchChronic obstructive pulmonary diseaseHeart failureCOPD statusEjection fractionN-terminal pro-B-type natriuretic peptide levelsHistory of COPDNew York Heart Association functional class IIPro-B-type natriuretic peptide levelsBaseline chronic obstructive pulmonary diseaseIntroduction Chronic obstructive pulmonary diseaseLower systolic blood pressureWorse NYHA functional classEfficacy of dapagliflozinHigher NT-proBNPPrior HF hospitalizationFunctional class IINatriuretic peptide levelsNYHA functional classEffect of dapagliflozinObstructive pulmonary diseaseSystolic blood pressureVentricular ejection fractionStructural heart diseaseHF hospitalizationCardiovascular deathEfficacy of dapagliflozin according to geographic regions in patients with heart failure: a patient-level pooled analysis of DAPA-HF and DELIVER
Kondo T, Vaduganathan V, Hernandez A, Lam C, Inzucchi S, Martinez F, De Boer R, Kosiborod M, Desai A, Kober L, Ponikowski P, Sabatine M, Shah S, Solomon S, Mcmurray J. Efficacy of dapagliflozin according to geographic regions in patients with heart failure: a patient-level pooled analysis of DAPA-HF and DELIVER. European Heart Journal 2023, 44: ehad655.979. DOI: 10.1093/eurheartj/ehad655.979.Peer-Reviewed Original ResearchLeft ventricular ejection fractionSafety of dapagliflozinHeart failureDAPA-HFPrimary outcomeEjection fractionMean baseline LVEFBaseline left ventricular ejection fractionPatient-level pooled analysisBackground clinical characteristicsBenefit of dapagliflozinEfficacy of dapagliflozinElevated natriuretic peptidesNatriuretic peptide levelsEffect of dapagliflozinMineralocorticoid receptor antagonistsVentricular ejection fractionCardiovascular deathClinical characteristicsDiscontinuation ratesStandard careHazard ratioPatient characteristicsNatriuretic peptidePooled analysisEfficacy of Dapagliflozin According to Heart Rate: A Patient-Level Pooled Analysis of DAPA-HF and DELIVER
Kondo T, Butt J, Curtain J, Jhund P, Docherty K, Claggett B, Vaduganathan M, Bachus E, Hernandez A, Lam C, Inzucchi S, Martinez F, de Boer R, Kosiborod M, Desai A, Køber L, Ponikowski P, Sabatine M, Solomon S, McMurray J. Efficacy of Dapagliflozin According to Heart Rate: A Patient-Level Pooled Analysis of DAPA-HF and DELIVER. Circulation Heart Failure 2023, 16: e010898. PMID: 37886880, DOI: 10.1161/circheartfailure.123.010898.Peer-Reviewed Original ResearchConceptsLeft ventricular ejection fractionReduced ejection fractionVentricular ejection fractionPatient-level pooled analysisBenefit of dapagliflozinEjection fractionHeart failureAtrial fibrillationBaseline heart rateSinus rhythmHeart ratePrimary outcomeDAPA-HFCardiovascular deathPooled analysisHR rangeEfficacy of dapagliflozinEffect of dapagliflozinHeart failure phenotypeHigher heart rateCardiovascular eventsHazard ratioHigh riskFailure phenotypePatientsContemporary Use and Implications of Beta-Blockers in Patients With HFmrEF or HFpEF The DELIVER Trial
Peikert A, Bart B, Vaduganathan M, Claggett B, Kulac I, Kosiborod M, Desai A, Jhund P, Lam C, Inzucchi S, Martinez F, de Boer R, Hernandez A, Shah S, Petersson M, Langkilde A, McMurray J, Solomon S, Vardeny O. Contemporary Use and Implications of Beta-Blockers in Patients With HFmrEF or HFpEF The DELIVER Trial. JACC Heart Failure 2023, 12: 631-644. PMID: 37767674, DOI: 10.1016/j.jchf.2023.09.007.Peer-Reviewed Original ResearchBeta-blocker useLeft ventricular ejection fractionHeart failureEjection fractionPrimary outcomeCardiovascular deathAmerican Heart Association/American CollegeSymptomatic heart failureKey secondary endpointVentricular ejection fractionLatest European SocietyCovariate-adjusted modelsSecondary endpointsPrespecified analysisAdverse eventsAmerica guidelinesComorbidity managementChronotropic responseClinical outcomesClinical eventsSafety outcomesAmerican CollegeHigh riskHFpEFLower riskHeart failure, chronic obstructive pulmonary disease and efficacy and safety of dapagliflozin in heart failure with mildly reduced or preserved ejection fraction: Insights from DELIVER
Butt J, Lu H, Kondo T, Bachus E, de Boer R, Inzucchi S, Jhund P, Kosiborod M, Lam C, Martinez F, Vaduganathan M, Solomon S, McMurray J. Heart failure, chronic obstructive pulmonary disease and efficacy and safety of dapagliflozin in heart failure with mildly reduced or preserved ejection fraction: Insights from DELIVER. European Journal Of Heart Failure 2023, 25: 2078-2090. PMID: 37634087, DOI: 10.1002/ejhf.3000.Peer-Reviewed Original ResearchConceptsChronic obstructive pulmonary diseaseModerate chronic obstructive pulmonary diseaseCOPD statusSafety of dapagliflozinObstructive pulmonary diseaseHeart failurePulmonary diseasePrimary outcomeEjection fractionWorse outcomesKansas City Cardiomyopathy Questionnaire scoreBenefit of dapagliflozinPre-specified analysisSevere pulmonary diseaseCardiovascular deathCause hospitalizationPrimary endpointTreatment discontinuationAdverse eventsClinical eventsQuestionnaire scoresPlaceboDapagliflozinPatientsKnown historyOutpatient Worsening Among Patients With Mildly Reduced and Preserved Ejection Fraction Heart Failure in the DELIVER Trial
Chatur S, Vaduganathan M, Claggett B, Cunningham J, Docherty K, Desai A, Jhund P, de Boer R, Hernandez A, Inzucchi S, Kosiborod M, Lam C, Martinez F, Shah S, Petersson M, Langkilde A, McMurray J, Solomon S. Outpatient Worsening Among Patients With Mildly Reduced and Preserved Ejection Fraction Heart Failure in the DELIVER Trial. Circulation 2023, 148: 1735-1745. PMID: 37632455, PMCID: PMC10664793, DOI: 10.1161/circulationaha.123.066506.Peer-Reviewed Original ResearchConceptsUrgent HF visitsComposite end pointHeart failureHF hospitalizationHF visitsHF eventsFirst presentationCardiovascular deathEnd pointEjection fractionSubsequent mortalitySubsequent deathEjection fraction heart failurePrimary end pointCardiovascular causesClinical decompensationPrespecified analysisAmbulatory carePatientsClinical relevanceSentinel eventsHospitalizationDapagliflozinDeathVisitsDapagliflozin in Patients With Heart Failure and Deterioration in Renal Function
Chatur S, Vaduganathan M, Claggett B, Mc Causland F, Desai A, Jhund P, de Boer R, Hernandez A, Inzucchi S, Kosiborod M, Lam C, Martinez F, Shah S, Sabatine M, Kober L, Ponikowski P, Merkely B, Petersson M, Langkilde A, McMurray J, Solomon S. Dapagliflozin in Patients With Heart Failure and Deterioration in Renal Function. Journal Of The American College Of Cardiology 2023, 82: 1854-1863. PMID: 37634707, DOI: 10.1016/j.jacc.2023.08.026.Peer-Reviewed Original ResearchConceptsDeterioration of eGFRHeart failureSafety outcomesKidney functionTreatment groupsTime-updated Cox proportional hazards modelsSodium-glucose cotransporter 2 inhibitorsComorbid chronic kidney diseaseCox proportional hazards modelPrimary composite outcomeChronic kidney diseaseCotransporter 2 inhibitorsEffect of dapagliflozinGlomerular filtration rateProportional hazards modelLives of patientsDAPA-HFDrug discontinuationCardiovascular deathCardiovascular outcomesStudy drugChronic heartComposite outcomeDapagliflozin treatmentPrimary outcomeEfficacy of Dapagliflozin According to Geographic Location of Patients With Heart Failure
Kondo T, Wang X, Yang M, Jhund P, Claggett B, Vaduganathan M, Hernandez A, Lam C, Inzucchi S, Martinez F, de Boer R, Kosiborod M, Desai A, Køber L, Ponikowski P, Sabatine M, Langkilde A, Petersson M, Zaozerska N, Bachus E, Solomon S, McMurray J. Efficacy of Dapagliflozin According to Geographic Location of Patients With Heart Failure. Journal Of The American College Of Cardiology 2023, 82: 1014-1026. PMID: 37610398, DOI: 10.1016/j.jacc.2023.05.056.Peer-Reviewed Original ResearchConceptsSafety of dapagliflozinHeart failurePrimary outcomeEjection fractionPatient-level pooled analysisBenefit of dapagliflozinEfficacy of dapagliflozinReduced ejection fractionEffect of dapagliflozinDAPA-HFCardiovascular deathClinical characteristicsDiscontinuation ratesPatient characteristicsPooled analysisDapagliflozinPatientsBackground treatmentEvent ratesInhibitor efficacyEfficacyGeographic regionsOutcomesTreatmentPrevious reports
2022
IGFBP-7 and Outcomes in Heart Failure With Reduced Ejection Fraction Findings From DAPA-HF
Adamson C, Welsh P, Docherty K, de Boer R, Diez M, Drożdż J, Dukát A, Inzucchi S, Køber L, Kosiborod M, Ljungman C, Martinez F, Ponikowski P, Sabatine M, Morrow D, Lindholm D, Hammarstedt A, Boulton D, Greasley P, Langkilde A, Solomon S, Sattar N, McMurray J, Jhund P. IGFBP-7 and Outcomes in Heart Failure With Reduced Ejection Fraction Findings From DAPA-HF. JACC Heart Failure 2022, 11: 291-304. PMID: 36592046, DOI: 10.1016/j.jchf.2022.09.004.Peer-Reviewed Original ResearchConceptsInsulin-like growth factor-binding protein 7IGFBP-7 levelsHeart failureN-terminal pro-B-type natriuretic peptidePro-B-type natriuretic peptideHigh-sensitivity troponin TCox proportional hazards modelBenefit of dapagliflozinDAPA-HF trialEjection fraction (EF) findingsIGFBP-7 concentrationsWorse clinical profileReduced ejection fractionAdverse clinical outcomesPotential prognostic biomarkerProportional hazards modelAdvanced HFrEFDAPA-HFCardiovascular deathHF outcomesNT-proBNPPrimary endpointClinical profileEjection fractionHighest tertileDapagliflozin in patients with heart failure with mildly reduced and preserved ejection fraction treated with a mineralocorticoid receptor antagonist or sacubitril/valsartan
Yang M, Butt J, Kondo T, Jering K, Docherty K, Jhund P, de Boer R, Claggett B, Desai A, Hernandez A, Inzucchi S, Kosiborod M, Lam C, Langkilde A, Martinez F, Petersson M, Shah S, Vaduganathan M, Wilderäng U, Solomon S, McMurray J. Dapagliflozin in patients with heart failure with mildly reduced and preserved ejection fraction treated with a mineralocorticoid receptor antagonist or sacubitril/valsartan. European Journal Of Heart Failure 2022, 24: 2307-2319. PMID: 36342375, PMCID: PMC11497302, DOI: 10.1002/ejhf.2722.Peer-Reviewed Original ResearchConceptsAngiotensin receptor neprilysin inhibitorMineralocorticoid receptor antagonistsSafety of dapagliflozinHeart failureEjection fractionPrimary outcomeReceptor antagonistRecent guidelinesSodium-glucose cotransporter 2 inhibitorsLower systolic blood pressureBenefit of dapagliflozinPrior HF hospitalizationSacubitril/valsartanCotransporter 2 inhibitorsEffect of dapagliflozinSystolic blood pressureARNI therapyHF hospitalizationCardiovascular deathAdverse eventsHazard ratioBlood pressureSGLT2 inhibitorsPatientsDapagliflozinRelationship between endothelin-1, heart failure with reduced ejection fraction and dapagliflozin: findings from DAPA-HF
Yeoh S, Docherty K, Jhund P, Hammarstedt A, Inzucchi S, Kober L, Kosiborod M, Martinez F, Ponikowski P, Solomon S, Sattar N, Welsh P, Sabatine M, Morrow D, McMurray J. Relationship between endothelin-1, heart failure with reduced ejection fraction and dapagliflozin: findings from DAPA-HF. European Heart Journal 2022, 43: ehac544.833. DOI: 10.1093/eurheartj/ehac544.833.Peer-Reviewed Original ResearchBaseline ET-1 concentrationET-1 concentrationsBaseline ET-1Benefit of dapagliflozinSerum ET-1Kidney functionEndothelin-1Tertile 3NT-proBNPPrimary outcomeCirculating Endothelin-1DAPA-HF trialEfficacy of dapagliflozinET-1 measurementsHeart Failure TrialReduced ejection fractionWorse functional statusET-1 levelsHeart failure outcomesHeart failure severityHigh-sensitivity troponinDAPA-HFCardiovascular deathEGFR slopeLower eGFRInfluence of NT-proBNP on Efficacy of Dapagliflozin in Heart Failure With Mildly Reduced or Preserved Ejection Fraction
Myhre P, Vaduganathan M, Claggett B, Miao Z, Jhund P, de Boer R, Hernandez A, Inzucchi S, Kosiborod M, Lam C, Martinez F, Shah S, Desai A, Lindholm D, Petersson M, Langkilde A, McMurray J, Solomon S. Influence of NT-proBNP on Efficacy of Dapagliflozin in Heart Failure With Mildly Reduced or Preserved Ejection Fraction. JACC Heart Failure 2022, 10: 902-913. PMID: 36114137, DOI: 10.1016/j.jchf.2022.08.007.Peer-Reviewed Original ResearchConceptsNT-proBNP concentrationsBaseline NT-proBNP concentrationHigher NT-proBNP concentrationsNT-proBNP levelsNT-proBNPHeart failureEjection fractionN-terminal pro-B-type natriuretic peptidePro-B-type natriuretic peptideBaseline NT-proBNP levelsHigher NT-proBNP levelsBaseline NT-proBNPEfficacy of dapagliflozinElevated NT-proBNPMedian baseline concentrationNT-proBNP quartilesSafety of dapagliflozinPlacebo-controlled trialPrimary composite outcomeAbsolute risk reductionPrevious clinical trialsGreater absolute benefitCardiovascular deathComposite outcomePrimary outcomeEffects of Dapagliflozin in Asian Patients With Heart Failure and Reduced Ejection Fraction in DAPA-HF
Docherty K, Anand I, Chiang C, Chopra V, Desai A, Kitakaze M, Verma S, Vinh P, Inzucchi S, Køber L, Kosiborod M, Martinez F, Bengtsson O, Ponikowski P, Sabatine M, Sjöstrand M, Solomon S, Langkilde A, Jhund P, McMurray J. Effects of Dapagliflozin in Asian Patients With Heart Failure and Reduced Ejection Fraction in DAPA-HF. JACC Asia 2022, 2: 139-153. PMID: 36339117, PMCID: PMC9627879, DOI: 10.1016/j.jacasi.2022.02.004.Peer-Reviewed Original ResearchDAPA-HF trialReduced ejection fractionEjection fractionCardiovascular deathAsian patientsHF eventsElevated N-terminal pro-B-type natriuretic peptideNew York Heart Association functional class IIN-terminal pro-B-type natriuretic peptidePro-B-type natriuretic peptideLeft ventricular ejection fractionSafety of dapagliflozinFunctional class IIEffect of dapagliflozinVentricular ejection fractionDAPA-HFDrug discontinuationHFrEF patientsPrimary endpointAdverse eventsHeart failurePrespecified outcomesPrimary outcomeNatriuretic peptideSame extent