2022
Central vs site outcome adjudication in the IRIS trial
Forman R, Viscoli CM, Bath PM, Furie KL, Guarino P, Inzucchi SE, Young L, Kernan WN. Central vs site outcome adjudication in the IRIS trial. Journal Of Stroke And Cerebrovascular Diseases 2022, 31: 106667. PMID: 35901589, DOI: 10.1016/j.jstrokecerebrovasdis.2022.106667.Peer-Reviewed Original ResearchConceptsCentral adjudicationHazard ratioStroke definitionsRecent transient ischemic attackInsulin Resistance InterventionMain secondary outcomesShorter symptom durationTransient ischemic attackPrevention of strokeNormal brain imagingClinical trial researchIschemic attackIschemic strokeSecondary outcomesSymptom durationPrimary outcomeStroke trialsIRIS trialMyocardial infarctionOutcome definitionsStroke typeOutcome eventsAdjudicated eventsOutcome adjudicationResistance InterventionEfficacy of lower doses of pioglitazone after stroke or transient ischaemic attack in patients with insulin resistance
Spence JD, Viscoli C, Kernan WN, Young LH, Furie K, DeFronzo R, Abdul‐Ghani M, Dandona P, Inzucchi SE. Efficacy of lower doses of pioglitazone after stroke or transient ischaemic attack in patients with insulin resistance. Diabetes Obesity And Metabolism 2022, 24: 1150-1158. PMID: 35253334, DOI: 10.1111/dom.14687.Peer-Reviewed Original ResearchConceptsNew-onset diabetesAdjusted hazard ratioHazard ratioLow dosesAdverse effectsInsulin Resistance InterventionTransient ischemic attackSecondary prevention strategiesAnti-atherosclerotic propertiesInsulin-sensitizing drugsLess adverse effectsIschemic attackStudy drugHeart failureStroke trialsAdverse outcomesInsulin resistancePioglitazonePrevention strategiesHigh dosesResistance InterventionFull doseWeight gainDiabetesPatients
2019
Pioglitazone Therapy in Patients With Stroke and Prediabetes
Spence JD, Viscoli CM, Inzucchi SE, Dearborn-Tomazos J, Ford GA, Gorman M, Furie KL, Lovejoy AM, Young LH, Kernan WN. Pioglitazone Therapy in Patients With Stroke and Prediabetes. JAMA Neurology 2019, 76: 526-535. PMID: 30734043, PMCID: PMC6515584, DOI: 10.1001/jamaneurol.2019.0079.Peer-Reviewed Original ResearchMeSH KeywordsAcute Coronary SyndromeAgedDiabetes Mellitus, Type 2Disease ProgressionFemaleGlycated HemoglobinHeart FailureHospitalizationHumansHypoglycemic AgentsInsulin ResistanceMaleMedication AdherenceMiddle AgedMyocardial InfarctionPioglitazonePrediabetic StateProportional Hazards ModelsRecurrenceSecondary PreventionStrokeConceptsAcute coronary syndromeStroke/myocardial infarctionTransient ischemic attackMyocardial infarctionCoronary syndromeHeart failureIRIS trialInsulin resistanceGood adherenceIschemic attackRecurrent strokeHazard ratioClinical trialsStroke/transient ischemic attackRandomized multicenter clinical trialAmerican Diabetes Association criteriaInsulin Resistance InterventionHemoglobin A1c levelsEffect of pioglitazoneInsulin-sensitizing agentsMulticenter clinical trialPlasma glucose levelsSerious bone fracturesPlacebo cohortPrior strokeAchievement of Guideline-Recommended Weight Loss Among Patients With Ischemic Stroke and Obesity
Dearborn JL, Viscoli CM, Young LH, Gorman MJ, Furie KL, Kernan WN. Achievement of Guideline-Recommended Weight Loss Among Patients With Ischemic Stroke and Obesity. Stroke 2019, 50: 713-717. PMID: 30786849, PMCID: PMC6391736, DOI: 10.1161/strokeaha.118.024008.Peer-Reviewed Original ResearchConceptsTransient ischemic attackBody mass indexProportion of patientsIschemic strokeMass indexVascular eventsBaseline weightWeight lossAchievement of guidelineDays of randomizationRecent ischemic strokeAcute ischemic strokeFuture vascular eventsIschemic attackPlacebo groupObese patientsDiabetes mellitusMedian ageTrial entryIRIS trialMedian timeFunctional outcomeInsulin resistanceClinical trialsPatients
2018
Scoring System to Optimize Pioglitazone Therapy After Stroke Based on Fracture Risk
Viscoli CM, Kent DM, Conwit R, Dearborn JL, Furie KL, Gorman M, Guarino PD, Inzucchi SE, Stuart A, Young LH, Kernan WN, Investigators F. Scoring System to Optimize Pioglitazone Therapy After Stroke Based on Fracture Risk. Stroke 2018, 50: 95-100. PMID: 30580725, PMCID: PMC6557695, DOI: 10.1161/strokeaha.118.022745.Peer-Reviewed Original ResearchTransient ischemic attackAbsolute risk differenceFracture riskIschemic attackPioglitazone therapyFracture risk modelsIschemic strokeMyocardial infarctionRisk strataRisk differenceRandomized placebo-controlled trialFavorable benefit-risk profilePlacebo-controlled trialLow-risk patientsEffect of pioglitazoneBody mass indexHigh-risk groupBenefit-risk profileHigh-risk stratumLow-risk groupSimple point scoreBone fracture riskCardiovascular riskPatient characteristicsDiabetes mellitusMetabolic syndrome identifies normal weight insulin-resistant stroke patients at risk for recurrent vascular disease
Dearborn JL, Viscoli CM, Inzucchi SE, Young LH, Kernan WN. Metabolic syndrome identifies normal weight insulin-resistant stroke patients at risk for recurrent vascular disease. International Journal Of Stroke 2018, 14: 639-645. PMID: 30507360, DOI: 10.1177/1747493018816425.Peer-Reviewed Original ResearchConceptsNormal weight patientsMetabolic syndromeMyocardial infarctionWeight patientsCause mortalityInsulin resistanceHigh riskInsulin Resistance InterventionRecent ischemic strokeRecurrent vascular diseaseNon-diabetic patientsTransient ischemic attackAdverse cardiovascular outcomesMajor comorbid conditionsIschemic attackCardiovascular outcomesObesity paradoxIschemic strokeNormal BMIObese patientsStroke populationBetter prognosisComorbid conditionsNormal weightStroke patientsHeart Failure After Ischemic Stroke or Transient Ischemic Attack in Insulin-Resistant Patients Without Diabetes Mellitus Treated With Pioglitazone
Young LH, Viscoli CM, Schwartz GG, Inzucchi SE, Curtis JP, Gorman MJ, Furie KL, Conwit R, Spatz E, Lovejoy A, Abbott JD, Jacoby DL, Kolansky DM, Ling FS, Pfau SE, Kernan WN. Heart Failure After Ischemic Stroke or Transient Ischemic Attack in Insulin-Resistant Patients Without Diabetes Mellitus Treated With Pioglitazone. Circulation 2018, 138: 1210-1220. PMID: 29934374, PMCID: PMC6202153, DOI: 10.1161/circulationaha.118.034763.Peer-Reviewed Original ResearchConceptsRisk of HFTransient ischemic attackEffect of pioglitazoneHF riskHeart failureInsulin-resistant patientsMyocardial infarctionIschemic attackCardiovascular benefitsIschemic strokeDiabetes mellitusInsulin resistanceHigher C-reactive proteinComposite of strokeHF risk scoreHigher HF riskDrug dose reductionHospitalized heart failureIncident myocardial infarctionLower mean doseC-reactive proteinBaseline patient featuresHF hospitalizationCardiovascular eventsPlacebo groupWhat Mediated Pioglitazone's Cardiovascular (CV) Benefit in the IRIS Trial?
INZUCCHI S, VISCOLI C, YOUNG L, GORMAN M, CONWIT R, SCHWARTZ G, KERNAN W. What Mediated Pioglitazone's Cardiovascular (CV) Benefit in the IRIS Trial? Diabetes 2018, 67 DOI: 10.2337/db18-17-lb.Peer-Reviewed Original ResearchTransient ischemic attackDensity lipoprotein cholesterolInsulin resistanceCV benefitsLog HRCardiovascular benefitsLipoprotein cholesterolBlood pressureStroke/transient ischemic attackHigh-sensitivity C-reactive proteinHigh-density lipoprotein cholesterolLow-density lipoprotein cholesterolMeasures of IRInsulin Resistance InterventionHomeostatic model assessmentDiastolic blood pressureEffect of pioglitazoneSystolic blood pressureC-reactive proteinFavorable effectBoehringer Ingelheim PharmaceuticalsPIO effectIschemic attackNondiabetic patientsHOMA-IR
2017
Targeting Pioglitazone Hydrochloride Therapy After Stroke or Transient Ischemic Attack According to Pretreatment Risk for Stroke or Myocardial Infarction
Kernan WN, Viscoli CM, Dearborn JL, Kent DM, Conwit R, Fayad P, Furie KL, Gorman M, Guarino PD, Inzucchi SE, Stuart A, Young LH. Targeting Pioglitazone Hydrochloride Therapy After Stroke or Transient Ischemic Attack According to Pretreatment Risk for Stroke or Myocardial Infarction. JAMA Neurology 2017, 74: 1319-1327. PMID: 28975241, PMCID: PMC5710663, DOI: 10.1001/jamaneurol.2017.2136.Peer-Reviewed Original ResearchConceptsTransient ischemic attackIschemic attackMyocardial infarctionIschemic strokeHigh riskPioglitazone groupInsulin resistanceLower riskCox proportional hazards regression modelProportional hazards regression modelsMedian riskEfficacy of pioglitazoneInsulin Resistance InterventionQualifying ischemic strokePlacebo-controlled trialHazards regression modelsLow baseline riskType 2 diabetesGreater absolute benefitDay of entryFuture strokeHydrochloride therapyPlacebo groupHazard ratioSecondary preventionPioglitazone Prevents Stroke in Patients With a Recent Transient Ischemic Attack or Ischemic Stroke
Yaghi S, Furie KL, Viscoli CM, Kamel H, Gorman M, Dearborn J, Young LH, Inzucchi SE, Lovejoy AM, Kasner SE, Conwit R, Kernan WN. Pioglitazone Prevents Stroke in Patients With a Recent Transient Ischemic Attack or Ischemic Stroke. Circulation 2017, 137: 455-463. PMID: 29084736, DOI: 10.1161/circulationaha.117.030458.Peer-Reviewed Original ResearchConceptsTransient ischemic attackIschemic strokeIschemic attackNondiabetic patientsStroke outcomeStroke eventsInsulin resistanceRecent transient ischemic attackCox proportional hazards modelQualifying ischemic strokeEffect of pioglitazoneFirst stroke eventProportional hazards modelPrevents strokeHemorrhagic eventsComposite outcomeSecondary preventionRecent strokeIRIS trialMyocardial infarctionTreatment groupsHazards modelPioglitazoneConsensus criteriaSurvival analysisResponse by Young et al to Letters Regarding Article, “Cardiac Outcomes After Ischemic Stroke or Transient Ischemic Attack
Young LH, Viscoli CM, Inzucchi SE, Kernan WN. Response by Young et al to Letters Regarding Article, “Cardiac Outcomes After Ischemic Stroke or Transient Ischemic Attack. Circulation 2017, 136: 1567-1568. PMID: 29038213, PMCID: PMC5683402, DOI: 10.1161/circulationaha.117.030513.Peer-Reviewed Case Reports and Technical NotesEffects of pioglitazone on cognitive function in patients with a recent ischaemic stroke or TIA: a report from the IRIS trial
Furie KL, Viscoli CM, Gorman M, Ford GA, Young LH, Inzucchi SE, Guarino PD, Lovejoy AM, Conwit R, Tanne D, Kernan WN. Effects of pioglitazone on cognitive function in patients with a recent ischaemic stroke or TIA: a report from the IRIS trial. Journal Of Neurology Neurosurgery & Psychiatry 2017, 89: 21. PMID: 28939682, DOI: 10.1136/jnnp-2017-316361.Peer-Reviewed Original ResearchConceptsTransient ischemic attackRecent ischemic strokeIschemic strokeCognitive functionHomeostasis model assessment insulin resistance scoreModified Mini-Mental State Examination scoresAssessment-insulin resistance scoreMini-Mental State Examination scoreInsulin Resistance InterventionPoststroke cognitive functionVascular risk factorsEffect of pioglitazoneInsulin-resistant patientsState Examination scoreIschemic attackPioglitazone groupPlacebo groupIRIS trialStroke trialsCerebrovascular diseaseInsulin resistanceRisk factorsCognitive dysfunctionPatientsResistance InterventionCardiac Outcomes After Ischemic Stroke or Transient Ischemic Attack
Young LH, Viscoli CM, Curtis JP, Inzucchi SE, Schwartz GG, Lovejoy AM, Furie KL, Gorman MJ, Conwit R, Abbott JD, Jacoby DL, Kolansky DM, Pfau SE, Ling FS, Kernan WN. Cardiac Outcomes After Ischemic Stroke or Transient Ischemic Attack. Circulation 2017, 135: 1882-1893. PMID: 28246237, PMCID: PMC5511545, DOI: 10.1161/circulationaha.116.024863.Peer-Reviewed Original ResearchConceptsAcute coronary syndromeType 1 myocardial infarctionTransient ischemic attackMyocardial infarctionCoronary syndromeInsulin resistanceIschemic attackIschemic strokeDiabetes mellitusSerum troponinAcute coronary syndrome episodeMean age 63 yearsAcute coronary syndrome eventIndependent clinical events committeeType 2 myocardial infarctionIRIS participantsImpact of pioglitazoneRecent cerebrovascular eventsRecent ischemic strokeClinical events committeeAge 63 yearsEffect of pioglitazoneSmall myocardial infarctionCoronary artery diseaseST-segment elevation
2016
Pioglitazone and Risk for Bone Fracture: Safety Data From a Randomized Clinical Trial
Viscoli CM, Inzucchi SE, Young LH, Insogna KL, Conwit R, Furie KL, Gorman M, Kelly MA, Lovejoy AM, Kernan WN, Investigators F. Pioglitazone and Risk for Bone Fracture: Safety Data From a Randomized Clinical Trial. The Journal Of Clinical Endocrinology & Metabolism 2016, 102: 914-922. PMID: 27935736, PMCID: PMC5460686, DOI: 10.1210/jc.2016-3237.Peer-Reviewed Original ResearchConceptsTransient ischemic attackIschemic strokeFracture riskBone fracturesRisk/benefit ratioAbsolute fracture riskInsulin Resistance InterventionPlacebo-treated patientsIschemic attackNondiabetic patientsPlacebo groupCardiovascular riskBone healthStroke trialsNondiabetic participantsPrevent fallsClinical trialsRelative riskSafety dataFracture classificationQuarterly interviewsPioglitazonePatientsResistance InterventionRisk incrementPioglitazone Prevents Diabetes in Patients With Insulin Resistance and Cerebrovascular Disease.
Inzucchi SE, Viscoli CM, Young LH, Furie KL, Gorman M, Lovejoy AM, Dagogo-Jack S, Ismail-Beigi F, Korytkowski MT, Pratley RE, Schwartz GG, Kernan WN. Pioglitazone Prevents Diabetes in Patients With Insulin Resistance and Cerebrovascular Disease. Diabetes Care 2016, 39: 1684-92. PMID: 27465265, PMCID: PMC5033078, DOI: 10.2337/dc16-0798.Peer-Reviewed Original ResearchConceptsTransient ischemic attackRecent ischemic strokeInsulin resistanceIschemic strokeHOMA-IRInsulin Resistance InterventionMajor cardiovascular eventsMean HOMA-IRHistory of diabetesSubsequent ischemic eventsHomeostasis model assessmentRisk of diabetesΜIU/mLFPG testingPioglitazone groupCardiovascular eventsIschemic attackPlacebo groupFirst medicationIschemic eventsMean FPGDiabetes onsetDiabetes preventionCerebrovascular diseaseStroke trialsPioglitazone after Ischemic Stroke or Transient Ischemic Attack
Kernan WN, Viscoli CM, Furie KL, Young LH, Inzucchi SE, Gorman M, Guarino PD, Lovejoy AM, Peduzzi PN, Conwit R, Brass LM, Schwartz GG, Adams HP, Berger L, Carolei A, Clark W, Coull B, Ford GA, Kleindorfer D, O'Leary JR, Parsons MW, Ringleb P, Sen S, Spence JD, Tanne D, Wang D, Winder TR. Pioglitazone after Ischemic Stroke or Transient Ischemic Attack. New England Journal Of Medicine 2016, 374: 1321-1331. PMID: 26886418, PMCID: PMC4887756, DOI: 10.1056/nejmoa1506930.Peer-Reviewed Original ResearchConceptsTransient ischemic attackIschemic strokeInsulin resistanceMyocardial infarctionIschemic attackPrimary outcomeRecent ischemic strokeDouble-blind trialFuture cardiovascular eventsHomeostasis model assessmentInsulin resistance indexRisk of strokeEligible patientsNonfatal strokePioglitazone groupCardiovascular eventsCause mortalityPlacebo groupPreventive therapyCerebrovascular diseaseInsulin sensitivityRisk factorsResistance indexHigh riskLower risk
2014
Pioglitazone for secondary prevention after ischemic stroke and transient ischemic attack: Rationale and design of the Insulin Resistance Intervention after Stroke Trial
Viscoli CM, Brass LM, Carolei A, Conwit R, Ford GA, Furie KL, Gorman M, Guarino PD, Inzucchi SE, Lovejoy AM, Parsons MW, Peduzzi PN, Ringleb PA, Schwartz GG, Spence JD, Tanne D, Young LH, Kernan WN, investigators I. Pioglitazone for secondary prevention after ischemic stroke and transient ischemic attack: Rationale and design of the Insulin Resistance Intervention after Stroke Trial. American Heart Journal 2014, 168: 823-829.e6. PMID: 25458644, PMCID: PMC4254508, DOI: 10.1016/j.ahj.2014.07.016.Peer-Reviewed Original ResearchMeSH KeywordsAdultCognition DisordersDose-Response Relationship, DrugDouble-Blind MethodFemaleHumansHypoglycemic AgentsInsulin ResistanceIschemic Attack, TransientMaleMiddle AgedMyocardial InfarctionPatient Outcome AssessmentPioglitazoneRisk AssessmentRisk FactorsSecondary PreventionStrokeSurvival AnalysisThiazolidinedionesConceptsTransient ischemic attackMyocardial infarctionIschemic attackVascular eventsIschemic strokeSecondary preventionIRIS trialInsulin resistanceHomeostasis model assessment-insulin resistanceModel assessment-insulin resistanceEffectiveness of pioglitazoneInsulin Resistance InterventionRecent ischemic strokeRecurrent vascular eventsAssessment-insulin resistanceIschemic vascular eventsAcute coronary syndromeInsulin-resistant patientsInsulin-sensitizing drugsEligible patientsIndex strokeNondiabetic patientsCardiovascular outcomesCause mortalityCoronary syndrome