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 stroke
2018
Metabolic 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 patientsWhat 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 preventionEffects 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 InterventionSmoking cessation and outcome after ischemic stroke or TIA
Epstein KA, Viscoli CM, Spence JD, Young LH, Inzucchi SE, Gorman M, Gerstenhaber B, Guarino PD, Dixit A, Furie KL, Kernan WN, Bladin C, Davis S, Wijeratne T, Levi C, Parsons M, Brodtmann A, Ng S, Archer J, Delcourt C, Winder T, Berger L, Boulanger J, Chan R, Spence J, Durocher A, Mackey A, Verreault S, Minuk J, Penn A, Shuaib A, Cote R, Selchen D, Bayer N, Sweet M, Malik S, Stotts G, Griewing B, Soda H, Weinhardt R, Berrouschot J, Stoll A, Witte O, Günther A, Bodechtel U, Schminke U, Hobohm C, Hetzel A, Lambeck J, Wartenberg K, Huttner H, Dittrich R, Nabavi D, Gröschel K, Thomalla G, Rosenkranz M, Jander S, Meisel A, Ludolph A, Althaus K, Huber R, Lorenz M, Tanne D, Merzlyak O, Bornstein N, Telman G, Lampl Y, Streifler J, Weller B, Ifergane G, Wirgin Y, Carolei A, Toni D, Stanzione P, Micieli G, Agnelli G, Caso V, Gandolfo C, Comi G, Consoli D, Rasura M, Di Lazzaro V, Dixit A, Jupp B, Shaw L, Salih I, Esisi B, Power M, Strain W, Elyas S, Manawadu D, Kalra L, O'Brien E, Warburton E, Chatterjee K, Hargroves D, Blight A, Moynihan B, Markus H, Macleod M, Broughton D, Rodgers H, Hlaing T, Muir S, Sajid M, Bath P, Price C, Sekaran L, Vahidassr D, Muir K, McIlmoyle J, Datta P, Davey R, Langhorne P, Stott D, Datta P, England T, Muhidden K, O'Connell J, Majmudar N, Schindler J, Clark W, Sethi P, Rordorf G, Kleindorfer D, Silliman S, Gorman M, Kelly M, Singleton L, Meyer B, Jackson C, Walker J, Ehtisham A, Goodpasture H, Wang D, Fayad P, Cordina S, Naritoku D, Chiu D, Lukovits T, Goddeau R, Clark‐Arbogast R, Leigh R, Wityk R, Pettigrew L, Tayal A, Jarouse J, Friday G, Sen S, Kim A, Johnston S, Elkins J, Barrett A, Leira E, Kelly A, Burgin S, Rempe D, Jacoby M, Hughes D, Majersik J, Skalabrin E, Lee J, Hsu C, Sundararajan S, Slivka A, Minagar A, Alicic R, Geraghty M, Kase C, Lansberg M, Albers G, Dietrich D, Hanna J, Gentile N, Santiago F, Katzan I, Ching M, Sawyer, Warwick T, Yilmaz E, Pedelty L, Schneck M, Coull B, Solenski N, Johnston K, Lee V, Prabhakaran S, Johnson M, Silverman I, Salgado M, Birkhahn R, Strawsburg R, Altafullah I, Cohen D, Zweifler R, Lee Kwen P, Hammer M, Vora N, Tietjen G, Albakri E, Dandapani B, Jickling G, Verro P, Roller M, Hughes R, Simpson J, Vidic T, Lash S, Sigsbee B, Rosenbaum D, Fonzetti P, Fleck J, Goldszmidt A, Alexandrov A, Halsey J, Hart R, Sattin J, Kumar S, Book D, Torbey M, Poock J, King M, Graham G, Sung G, Mirsen T, Dromerick A, Runheim A, Jackson C, Feen E, Reichwein R, Waters M, Amory C, Bernardini G, Bell R, Diamond B, Rosenbaum D, Palestrant D, Segal A, Burger K, Schwartz R, Mitsias P, Kramer J, Kramer J, Robbins D, Silver B, Easton J, Feldmann E, Rymer M, Dorssom J, Ali L, Ovbiagele B, Kirshner H. Smoking cessation and outcome after ischemic stroke or TIA. Neurology 2017, 89: 1723-1729. PMID: 28887378, PMCID: PMC5644463, DOI: 10.1212/wnl.0000000000004524.Peer-Reviewed Original ResearchConceptsMyocardial infarctionIschemic strokeIndex eventProspective observational cohort studyInsulin Resistance InterventionHistory of hypertensionObservational cohort studyDiastolic blood pressureHistory of strokeCoronary artery diseaseTime of randomizationTobacco use historySignificant health benefitsRecurrent strokeNondiabetic menCohort studyCurrent smokersTrial cohortArtery diseaseBlood pressurePrimary outcomeIRIS trialStroke trialsCigarette smokingSmoking cessationPioglitazone and cardiovascular risk reduction
Perdigoto AL, Young LH, Inzucchi SE. Pioglitazone and cardiovascular risk reduction. Cardiovascular Endocrinology & Metabolism 2017, 6: 55-61. PMID: 31646121, PMCID: PMC6768516, DOI: 10.1097/xce.0000000000000110.Peer-Reviewed Original ResearchInsulin Resistance InterventionCV outcomesInsulin resistanceResistance InterventionImpact of thiazolidinedionesCardiovascular risk reductionGlucose-lowering drugsCardiovascular disease riskInsulin-resistant patientsType 2 diabetesCV complicationsMacrovascular eventsCV riskSecondary preventionResistant patientsStroke patientsStroke trialsPathophysiological abnormalitiesAntihyperglycemic agentsInsulin sensitivityDiabetes managementClinical practiceStroke resultsPatientsDisease risk
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 trials
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
2009
Boosting enrollment in neurology trials with Local Identification and Outreach Networks (LIONs)
Kernan WN, Viscoli CM, DeMarco D, Mendes B, Shrauger K, Schindler JL, McVeety JC, Sicklick A, Moalli D, Greco P, Bravata DM, Eisen S, Resor L, Sena K, Story D, Brass LM, Furie KL, Gutmann L, Hinnau E, Gorman M, Lovejoy AM, Inzucchi SE, Young LH, Horwitz RI. Boosting enrollment in neurology trials with Local Identification and Outreach Networks (LIONs). Neurology 2009, 72: 1345-1351. PMID: 19365056, PMCID: PMC2677492, DOI: 10.1212/wnl.0b013e3181a0fda3.Peer-Reviewed Original ResearchConceptsOutreach NetworkCentral coordinating centerInsulin Resistance InterventionSecondary stroke preventionNames of patientsResults of surveillanceStroke preventionMore patientsStroke siteConnecticut hospitalsTrial participantsHome visitsPatientsResistance InterventionPersonal physicianElectronic admissionRandomization ratesCoordinating CenterMore rapid completionMonthsHigher enrollment ratesHospitalRecruitment strategiesTrialsParticipants