Filipe A Moura, MD, PhD
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2025
Olezarsen for Managing Severe Hypertriglyceridemia and Pancreatitis Risk
Marston N, Bergmark B, Alexander V, Prohaska T, Kang Y, Moura F, Zimerman A, Waldman E, Weinland J, Murphy S, Goodrich E, Zhang S, Xia S, Li D, Goldberg A, Goudev A, Badimon L, Kiss R, Vrablik M, Gaudet D, Moulin P, Stroes E, Banach M, Cohen H, Blom D, Charng M, Nordestgaard B, Nicholls S, Tsimikas S, Giugliano R, Sabatine M. Olezarsen for Managing Severe Hypertriglyceridemia and Pancreatitis Risk. The New England Journal Of Medicine 2025 PMID: 41211918, DOI: 10.1056/nejmoa2512761.Peer-Reviewed Original ResearchIncidence of acute pancreatitisSevere hypertriglyceridemiaTriglyceride levelsAcute pancreatitisApolipoprotein C-IIIPlacebo-adjusted least-squares mean changeRemnant cholesterolNon-high-density lipoprotein (non-HDL) cholesterolLeast-squares mean changeRisk of acute pancreatitisAcute pancreatitis eventPlacebo-adjusted changePlacebo-controlled trialHepatic fat fractionLiver enzyme levelsDose-dependent increaseNon-HDL cholesterolLevels of triglyceridesC-IIIPlacebo monthDouble-blindPancreatitis eventsPlacebo groupDose groupPancreatitis riskAntibody-mediated LOX-1 inhibition in patients with residual inflammation after myocardial infarction: a randomized phase 2 trial
O’Donoghue M, Morrow D, Vavere A, Kardassis D, Moura F, Fagundes A, Ardissino D, Blaha V, Farkouh M, Kato E, Kimura T, Kiss R, Ophuis T, Selvanayagam J, Lopez-Sendon J, Wojakowski W, Zaman A, Lima J, Lu M, Foldyna B, Kuder J, Park J, Murphy S, Turton M, Collén A, Gabrielsen A, George R, Sabatine M. Antibody-mediated LOX-1 inhibition in patients with residual inflammation after myocardial infarction: a randomized phase 2 trial. Nature Medicine 2025, 31: 3553-3559. PMID: 40999229, DOI: 10.1038/s41591-025-03951-w.Peer-Reviewed Original ResearchConceptsLectin-like oxidized low-density lipoprotein (LDL) receptor-1Residual inflammationSoluble LOX-1Plaque volumeMyocardial infarctionRate of serious adverse eventsNoncalcified coronary plaque volumeInterleukin-6Randomized phase 2 trialLow-attenuation plaque volumePlacebo-adjusted reductionsOxidized low-density lipoprotein cholesterolLow-density lipoprotein cholesterolCoronary plaque volumePhase 2 trialDose-finding studySerious adverse eventsComputed tomography angiographyLOX-1 inhibitionDiseased coronary segmentsDose armDouble-blindPlacebo groupExploratory endpointsPrimary endpointTargeting APOC3 with Olezarsen in Moderate Hypertriglyceridemia
Bergmark B, Marston N, Prohaska T, Alexander V, Zimerman A, Moura F, Kang Y, Weinland J, Murphy S, Goodrich E, Zhang S, Li D, Banach M, Stroes E, Lu M, Tsimikas S, Giugliano R, Sabatine M. Targeting APOC3 with Olezarsen in Moderate Hypertriglyceridemia. The New England Journal Of Medicine 2025, 393: 1279-1291. PMID: 40888739, DOI: 10.1056/nejmoa2507227.Peer-Reviewed Original ResearchModerate hypertriglyceridemiaElevated cardiovascular riskTriglyceride levelsPlacebo-adjusted least-squares mean changeLeast-squares mean percent changesCardiovascular riskIncidence of serious adverse eventsLeast-squares mean changePlacebo-controlled trialBaseline to 6 monthsMedian triglyceride levelsSerious adverse eventsMessenger RNAApolipoprotein C-IIIDouble-blindPlacebo groupSevere hypertriglyceridemiaMedian ageDose groupAdverse eventsHypertriglyceridemiaTriglyceride clearancePrimary outcomeMean changePlaceboDetection of Hypertrophic Cardiomyopathy on Electrocardiogram Using Artificial Intelligence
Hillis J, Bizzo B, Mercaldo S, Ghatak A, MacDonald A, Halle M, Schultz A, L’Italien E, Tam V, Bart N, Moura F, Awad A, Bargiela D, Dagen S, Toland D, Blood A, Gross D, Jering K, Lopes M, Marston N, Nauffal V, Dreyer K, Scirica B, Ho C. Detection of Hypertrophic Cardiomyopathy on Electrocardiogram Using Artificial Intelligence. Circulation Heart Failure 2025, 18: e012667. PMID: 40365710, DOI: 10.1161/circheartfailure.124.012667.Peer-Reviewed Original ResearchHypertrophic cardiomyopathyDetection of hypertrophic cardiomyopathyAssociated with significant morbidityPredictive valueNegative predictive valueArea under the curvePositive predictive valueSudden cardiac deathSignificant morbidityChart reviewCardiac deathScreening electrocardiogramDiagnostic codesCardiac imagingClinical expertisePopulation prevalenceBinary outcomesCardiomyopathyElectrocardiogramDiagnosisImprove detectionPrevalenceElectrocardiogram featuresDISCOVERY AND VALIDATION OF PLASMA RENIN AND TNF-RELATED APOPTOSIS-INDUCING LIGAND (TRAIL) AS CIRCULATING BIOMARKERS OF HEART FAILURE RISK IN PATIENTS WITH TYPE 2 DIABETES MELLITUS
Berg D, Moura F, Bellavia A, Goodrich E, Scirica B, Wiviott S, Feinberg M, Morrow D, Sabatine M. DISCOVERY AND VALIDATION OF PLASMA RENIN AND TNF-RELATED APOPTOSIS-INDUCING LIGAND (TRAIL) AS CIRCULATING BIOMARKERS OF HEART FAILURE RISK IN PATIENTS WITH TYPE 2 DIABETES MELLITUS. Journal Of The American College Of Cardiology 2025, 85: 1528. DOI: 10.1016/s0735-1097(25)02012-1.Peer-Reviewed Original ResearchOlezarsen in patients with hypertriglyceridemia at high cardiovascular risk: Rationale and design of the Essence–TIMI 73b trial
Bergmark B, Marston N, Prohaska T, Alexander V, Zimerman A, Moura F, Kang Y, Murphy S, Zhang S, Lu M, Karwatowska-Prokopczuk E, Tsimikas S, Giugliano R, Sabatine M. Olezarsen in patients with hypertriglyceridemia at high cardiovascular risk: Rationale and design of the Essence–TIMI 73b trial. American Heart Journal 2025, 286: 116-124. PMID: 40081744, PMCID: PMC12065083, DOI: 10.1016/j.ahj.2025.02.022.Peer-Reviewed Original ResearchMeSH KeywordsAgedApolipoprotein C-IIICardiovascular DiseasesClinical Trials, Phase III as TopicComputed Tomography AngiographyCoronary AngiographyDouble-Blind MethodFemaleHeart Disease Risk FactorsHumansHypertriglyceridemiaMaleMiddle AgedOligonucleotidesOligonucleotides, AntisenseRandomized Controlled Trials as TopicTriglyceridesConceptsCoronary Computed Tomography AngiographyCardiovascular riskTriglyceride levelsModerate hypertriglyceridemiaBaseline coronary computed tomography angiographyPlacebo-controlled phase 3 trialClearance of triglyceride-rich lipoproteinsApoC-IIIBaseline triglyceride levelsBaseline to 6 monthsLipid-Lowering TherapyAntisense oligonucleotidesNoncalcified coronary plaquesPhase 3 trialComputed tomography angiographyLowering triglyceride levelsIncreased cardiovascular riskElevated cardiovascular riskReduce cardiovascular riskAtherosclerotic cardiovascular diseaseTriglyceride-rich lipoproteinsPotential therapeutic strategyPooled placeboApolipoprotein C-IIIDouble-blindDesign and rationale of the CORE-TIMI 72a and CORE2-TIMI 72b trials of olezarsen in patients with severe hypertriglyceridemia
Marston N, Bergmark B, Alexander V, Karwatowska-Prokopczuk E, Kang Y, Moura F, Prohaska T, Zimerman A, Zhang S, Murphy S, Tsimikas S, Giugliano R, Sabatine M. Design and rationale of the CORE-TIMI 72a and CORE2-TIMI 72b trials of olezarsen in patients with severe hypertriglyceridemia. American Heart Journal 2025, 286: 125-135. PMID: 40064331, PMCID: PMC12065585, DOI: 10.1016/j.ahj.2025.03.003.Peer-Reviewed Original ResearchConceptsSevere hypertriglyceridemiaAcute pancreatitis eventInvestigated antisense oligonucleotidesBaseline to 6 monthsPhase 3 trialTriglyceride-rich remnantsBaseline triglyceridesMatching placeboApolipoprotein C-IIIPancreatitis eventsMedian ageInhibit lipoprotein lipasePooled analysisClinical consequencesMRI substudyHypertriglyceridemiaSerum triglyceridesTG clearanceLife-threateningPatientsStudy populationApoC-IIIHepatic uptakeAntisense oligonucleotidesDedicated trialsIdentification of plasma proteomic markers underlying polygenic risk of type 2 diabetes and related comorbidities
Loesch D, Garg M, Matelska D, Vitsios D, Jiang X, Ritchie S, Sun B, Runz H, Whelan C, Holman R, Mentz R, Moura F, Wiviott S, Sabatine M, Udler M, Gause-Nilsson I, Petrovski S, Oscarsson J, Nag A, Paul D, Inouye M. Identification of plasma proteomic markers underlying polygenic risk of type 2 diabetes and related comorbidities. Nature Communications 2025, 16: 2124. PMID: 40032831, PMCID: PMC11876343, DOI: 10.1038/s41467-025-56695-z.Peer-Reviewed Original ResearchMeSH KeywordsBiomarkersCardiovascular DiseasesComorbidityDiabetes Mellitus, Type 2Extracellular Matrix ProteinsFemaleGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansInsulin-Like Growth Factor Binding Protein 2MaleMiddle AgedMultifactorial InheritanceProteomicsRisk FactorsUnited KingdomConceptsPolygenic scoresNon-coding variantsEtiology of type 2 diabetesMolecular dataVariant effectsPathway enrichmentPlasma proteomic markersPotential therapeutic targetType 2 diabetesProteinDisease biologyPolygenic riskUK BiobankProteomic markersTherapeutic targetPathwayCirculating proteinsGenomeRisk of type 2 diabetesCardiometabolic scoreBiologyInteractive portalVariantsEnrichmentDiabetes comorbiditiesSkeletal muscle adiposity, coronary microvascular dysfunction, and adverse cardiovascular outcomes
do A H Souza A, Troschel A, Marquardt J, Hadžić I, Foldyna B, Moura F, Hainer J, Divakaran S, Blankstein R, Dorbala S, Di Carli M, Aerts H, Lu M, Fintelmann F, Taqueti V. Skeletal muscle adiposity, coronary microvascular dysfunction, and adverse cardiovascular outcomes. European Heart Journal 2025, 46: 1112-1123. PMID: 39827905, DOI: 10.1093/eurheartj/ehae827.Peer-Reviewed Original ResearchCoronary microvascular dysfunctionBody mass indexCoronary flow reserveIntermuscular adipose tissueSubcutaneous adipose tissueHeart failureFat infiltrationMarker of coronary microvascular dysfunctionPRESERVED LEFT VENTRICULAR EJECTION FRACTIONCardiovascular outcomesAssociated with coronary microvascular dysfunctionHigher IMATIncreased IMATPresence of coronary microvascular dysfunctionSkeletal muscleFlow reserveIncreased risk of MACEMyocardial infarctionStress positron emission tomographyAssociated with increased MACERisk of heart failureLow coronary flow reserveThoracic vertebra levelVentricular ejection fractionIntermuscular adipose tissue areaA Bayesian Interpretation of CABANA and Other Randomized Controlled Trials for Catheter Ablation in Patients With Atrial Fibrillation
Nogueira A, Felix N, Kalil F, Tramujas L, Godoi A, Miyawaki I, Bellavia A, Moura F, Cardoso R, d'Avila A, Fernandes G. A Bayesian Interpretation of CABANA and Other Randomized Controlled Trials for Catheter Ablation in Patients With Atrial Fibrillation. Journal Of Cardiovascular Electrophysiology 2025, 36: 617-624. PMID: 39834105, DOI: 10.1111/jce.16552.Peer-Reviewed Original ResearchConceptsBayesian analysisTreatment effect distributionAdverse cardiovascular outcomesAll-Cause MortalityCardiovascular outcomesRandomized Controlled TrialsFrequentist estimatorsCatheter ablationMedical therapyAtrial fibrillationBayesian interpretationImpact of catheter ablationControlled TrialsAnalysis of randomized controlled trialsProbability distributionAtrial fibrillation patientsReduce adverse cardiovascular outcomesImpact of ablationEffective distributionRandom-effects modelBayes' theoremTrial-level dataProbabilistic understandingSurvival outcomesFibrillation patients
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Everyone Robert R Attaran, FACC, FSCAI, RPVI, MBBSMeeting ID: 956 3859 5269
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