2024
Decline in Estimated Glomerular Filtration Rate After Dapagliflozin in Heart Failure With Mildly Reduced or Preserved Ejection Fraction
Mc Causland F, Claggett B, Vaduganathan M, Desai A, Jhund P, Vardeny O, Fang J, de Boer R, Docherty K, Hernandez A, Inzucchi S, Kosiborod M, Lam C, Martinez F, Saraiva J, McGrath M, Shah S, Verma S, Langkilde A, Petersson M, McMurray J, Solomon S. Decline in Estimated Glomerular Filtration Rate After Dapagliflozin in Heart Failure With Mildly Reduced or Preserved Ejection Fraction. JAMA Cardiology 2024, 9: 144-152. PMID: 37952176, PMCID: PMC10641768, DOI: 10.1001/jamacardio.2023.4664.Peer-Reviewed Original ResearchSodium-glucose cotransporter 2 inhibitorsEGFR declineGlomerular filtration rateEjection fractionHeart failurePrespecified analysisFiltration rateMonths 1Estimated glomerular filtration rateDapagliflozin-treated patientsKidney composite outcomePrimary cardiovascular outcomeHeart Failure TrialChronic kidney diseaseCotransporter 2 inhibitorsInternational multicenter studyLives of patientsBaseline eGFRKidney eventsKidney outcomesCardiovascular outcomesComposite outcomePrognostic factorsFailure TrialMulticenter studyCardiac And Kidney Benefits Of Dapagliflozin Are Associated With ApoM Levels In Patients With Heart Failure With Reduced Ejection Fraction
Chang J, Javaheri A, Sauer A, Windsor S, Fu Z, Jones P, Margulies K, Lanfear D, Nassif M, Husain M, Inzucchi S, McGuire D, Pitt B, Scirica B, Kosiborod M. Cardiac And Kidney Benefits Of Dapagliflozin Are Associated With ApoM Levels In Patients With Heart Failure With Reduced Ejection Fraction. Journal Of Cardiac Failure 2024, 30: 236. DOI: 10.1016/j.cardfail.2023.10.284.Peer-Reviewed Original ResearchSodium-glucose cotransporter 2 inhibitorsUrine albumin-creatinine ratioLog-transformed NT-proBNPLog-transformed NT-proBNP levelsDapagliflozin-treated patientsNT-proBNP levelsReduced ejection fractionNT-proBNPHeart failureApoM levelsEjection fractionType 2 diabetes mellitusPlacebo-treated patientsAlbumin-creatinine ratioCotransporter 2 inhibitorsEffect of dapagliflozinMultivariable linear regressionSphingosine-1-PhosphateKidney benefitsSGLT2i dapagliflozinDapagliflozin groupHF trialsPlacebo groupDapagliflozin treatmentOverall cohort
2023
Effect of dapagliflozin on outpatient worsening heart failure in patients with mildly reduced or preserved ejection fraction: the DELIVER trial
Chatur S, Vaduganathan M, Claggett B, Desai A, Docherty K, Jhund P, De Boer R, Hernandez A, Inzucchi S, Kosiborod M, Lam C, Martinez F, Shah S, Mcmurray J, Solomon S. Effect of dapagliflozin on outpatient worsening heart failure in patients with mildly reduced or preserved ejection fraction: the DELIVER trial. European Heart Journal 2023, 44: ehad655.751. DOI: 10.1093/eurheartj/ehad655.751.Peer-Reviewed Original ResearchUrgent HF visitsHeart failureHF eventsHF hospitalizationHF visitsEjection fractionFirst presentationSubsequent mortalityComposite endpointSubsequent deathEffect of dapagliflozinTreatment effectsBackground HospitalizationCV causesCV deathDose uptitrationPrimary endpointPrognostic importanceClinical trialsFirst manifestationLandmark analysisAmbulatory careHospitalizationClinical relevancePatientsEffects 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 phenotypePatientsDapagliflozin and Apparent Treatment-Resistant Hypertension in Heart Failure With Mildly Reduced or Preserved Ejection Fraction: The DELIVER Trial
Ostrominski J, Vaduganathan M, Selvaraj S, Claggett B, Miao Z, Desai A, Jhund P, Kosiborod M, Lam C, Inzucchi S, Martinez F, de Boer R, Hernandez A, Shah S, Petersson M, Langkilde A, McMurray J, Solomon S. Dapagliflozin and Apparent Treatment-Resistant Hypertension in Heart Failure With Mildly Reduced or Preserved Ejection Fraction: The DELIVER Trial. Circulation 2023, 148: 1945-1957. PMID: 37830208, DOI: 10.1161/circulationaha.123.065254.Peer-Reviewed Original ResearchConceptsApparent treatment-resistant hypertensionBaseline blood pressureTreatment-resistant hypertensionVentricular ejection fractionEjection fractionNonresistant hypertensionPrimary outcomeHeart failureBP categoriesHigher left ventricular ejection fractionSystolic baseline blood pressureLeft ventricular ejection fractionRelative treatment benefitSerious adverse eventsKey secondary outcomesRisk of hypotensionWorse kidney functionHigh-risk populationProportion of participantsBaseline BP categoriesGreater absolute reductionCardiometabolic comorbiditiesHypertension groupVascular eventsAdverse eventsImpact of COVID‐19 in patients with heart failure with mildly reduced or preserved ejection fraction enrolled in the DELIVER trial
Bhatt A, Kosiborod M, Claggett B, Miao Z, Vaduganathan M, Lam C, Hernandez A, Martinez F, Inzucchi S, Shah S, de Boer R, Jhund P, Desai A, Fang J, Han Y, Comin‐Colet J, Drożdż J, Vardeny O, Merkely B, Lindholm D, Peterson M, Langkilde A, McMurray J, Solomon S. Impact of COVID‐19 in patients with heart failure with mildly reduced or preserved ejection fraction enrolled in the DELIVER trial. European Journal Of Heart Failure 2023, 25: 2177-2188. PMID: 37771274, DOI: 10.1002/ejhf.3043.Peer-Reviewed Original ResearchCOVID-19 diagnosisRisk of deathHeart failureEjection fractionPandemic onsetTrial participantsCOVID-19Death rateMajor hypoglycaemic eventsChronic heart failureTime of diagnosisCOVID-19 survivorsDiabetic ketoacidosisHypoglycaemic eventsClinical outcomesHF eventsCOVID-19 casesTreatment benefitClinical riskCardiovascular trialsDeath/DapagliflozinEvent ratesPatientsDiagnosisContemporary 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 eventsHospitalizationDapagliflozinDeathVisitsEfficacy 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 reportsDapagliflozin and Physical and Social Activity Limitations in Heart Failure With Reduced Ejection Fraction
Butt J, Docherty K, Kosiborod M, Inzucchi S, Køber L, Langkilde A, Martinez F, Bengtsson O, Ponikowski P, Sabatine M, Sjöstrand M, Solomon S, Jhund P, McMurray J. Dapagliflozin and Physical and Social Activity Limitations in Heart Failure With Reduced Ejection Fraction. JACC Heart Failure 2023, 11: 1411-1423. PMID: 37318419, DOI: 10.1016/j.jchf.2023.04.016.Peer-Reviewed Original ResearchConceptsKansas City Cardiomyopathy QuestionnaireActivity limitation scoresEffect of dapagliflozinLimitation scoresSocial activity limitationsHeart failureActivity limitationsDAPA-HF trialReduced ejection fractionProportion of patientsActivity limitation domainLimitation domainEjection fractionPhysical functionChronic diseasesDapagliflozinPatientsHealth statusPlaceboMixed-effects modelsMonthsBaselineComplete dataScoresSocial limitationsDapagliflozin and Kidney Outcomes in Patients With Heart Failure With Mildly Reduced or Preserved Ejection Fraction
Mc Causland F, Claggett B, Vaduganathan M, Desai A, Jhund P, de Boer R, Docherty K, Fang J, Hernandez A, Inzucchi S, Kosiborod M, Lam C, Martinez F, Saraiva J, McGrath M, Shah S, Verma S, Langkilde A, Petersson M, McMurray J, Solomon S. Dapagliflozin and Kidney Outcomes in Patients With Heart Failure With Mildly Reduced or Preserved Ejection Fraction. JAMA Cardiology 2023, 8: 56-65. PMID: 36326604, PMCID: PMC9634592, DOI: 10.1001/jamacardio.2022.4210.Peer-Reviewed Original ResearchConceptsBaseline kidney functionKidney composite outcomeEffect of dapagliflozinEjection fractionHeart failureKidney outcomesComposite outcomePrimary outcomeKidney functionKidney diseaseSodium-glucose cotransporter 2 inhibitorsBaseline eGFR categoryBaseline kidney diseaseBenefit of dapagliflozinComposite kidney outcomeHeart Failure TrialReduced ejection fractionCotransporter 2 inhibitorsHeart failure eventsGlomerular filtration rateOverall incidence rateOverall event rateLives of patientsTreatment effectsEGFR categories
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 inhibitorsPatientsDapagliflozinStroke in patients with heart failure and reduced ejection fraction without atrial fibrillation: external validation of a risk model
Kondo T, Jhund P, Abraham W, Rouleau J, Packer M, Desai A, Kober L, Solomon S, Zile M, Inzucchi S, Kosiborod M, Sabatine M, Ponikowski P, Martinez F, McMurray J. Stroke in patients with heart failure and reduced ejection fraction without atrial fibrillation: external validation of a risk model. European Heart Journal 2022, 43: ehac544.869. DOI: 10.1093/eurheartj/ehac544.869.Peer-Reviewed Original ResearchAtrial fibrillationHeart failureRisk scoreEjection fractionHistory of AFRisk/benefit profileBackground Heart failureCardio-embolic strokeDAPA-HF trialModern pharmacological therapyProphylactic anticoagulant therapyRisk/benefit balanceReduced ejection fractionRisk of strokeIdentification of patientsInsulin-treated diabetesProbability of strokePatient-level dataSimple risk modelStroke prediction modelsHFrEF patientsProphylactic anticoagulationHF patientsNT-proBNPPARADIGM-HFOutcomes related to IGFBP-7 in patients with heart failure and reduced ejection fraction and effects of dapagliflozin: findings from DAPA-HF
Adamson C, Welsh P, Morrow D, Docherty K, Hammarstedt A, Inzucchi S, Kober L, Kosiborod M, Martinez F, Ponikowski P, Sabatine M, Solomon S, Sattar N, Jhund P, McMurray J. Outcomes related to IGFBP-7 in patients with heart failure and reduced ejection fraction and effects of dapagliflozin: findings from DAPA-HF. European Heart Journal 2022, 43: ehac544.913. DOI: 10.1093/eurheartj/ehac544.913.Peer-Reviewed Original ResearchIGFBP-7 levelsAdjusted hazard ratioReduced ejection fractionEffect of dapagliflozinIGFBP-7NT-proBNPPrimary outcomeEjection fractionHeart failureDAPA-HFNYHA classCause mortalityHF eventsHighest thirdCorresponding adjusted hazard ratioMore type 2 diabetesHigh-sensitivity troponin TInsulin-like growth factor binding protein 7Growth factor binding protein 7Adverse HF outcomesBenefit of dapagliflozinDAPA-HF trialEfficacy of dapagliflozinHigher NYHA classNYHA class IIBlood Pressure and Dapagliflozin in Heart Failure With Mildly Reduced or Preserved Ejection Fraction DELIVER
Selvaraj S, Vaduganathan M, Claggett B, Miao Z, Fang J, Vardeny O, Desai A, Shah S, Lam C, Martinez F, Inzucchi S, de Boer R, Petersson M, Langkilde A, McMurray J, Solomon S. Blood Pressure and Dapagliflozin in Heart Failure With Mildly Reduced or Preserved Ejection Fraction DELIVER. JACC Heart Failure 2022, 11: 76-89. PMID: 36599553, DOI: 10.1016/j.jchf.2022.09.002.Peer-Reviewed Original ResearchConceptsSystolic blood pressureBlood pressureHeart failureSBP categoriesEjection fractionPrimary outcomeKansas City Cardiomyopathy Questionnaire total symptom scoreTreatment effectsSodium-glucose cotransporter 2 inhibitorsBaseline systolic blood pressureBlood pressure-lowering effectHigher systolic blood pressureHigher heart failureClass I recommendationCotransporter 2 inhibitorsPressure-lowering effectTotal symptom scoreCardiovascular outcomesAdverse eventsAntihypertensive effectSecondary outcomesStroke riskI recommendationSymptom scoresCardiovascular diseaseInfluence 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 outcome