2018
Cardiovascular event reduction with PCSK9 inhibition among 1578 patients with familial hypercholesterolemia: Results from the SPIRE randomized trials of bococizumab
Ridker PM, Rose LM, Kastelein JJP, Santos RD, Wei C, Revkin J, Yunis C, Tardif JC, Shear CL, Investigators S. Cardiovascular event reduction with PCSK9 inhibition among 1578 patients with familial hypercholesterolemia: Results from the SPIRE randomized trials of bococizumab. Journal Of Clinical Lipidology 2018, 12: 958-965. PMID: 29685591, DOI: 10.1016/j.jacl.2018.03.088.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntibodies, Anti-IdiotypicAntibodies, Monoclonal, HumanizedAnticholesteremic AgentsCardiovascular DiseasesCholesterol, LDLFemaleHumansHydroxymethylglutaryl-CoA Reductase InhibitorsHyperlipoproteinemia Type IIMaleMiddle AgedPlacebo EffectProportional Hazards ModelsProprotein Convertase 9Risk FactorsConceptsProprotein convertase subtilisin kexin type 9Major adverse cardiovascular eventsAdverse cardiovascular eventsPCSK9 inhibitionNon-FH patientsFH patientsCardiovascular eventsFamilial hypercholesterolemiaMean (SD) baseline LDL-C levelElevated low-density lipoprotein cholesterolFuture cardiovascular event ratesBaseline LDL-C levelsLow-density lipoprotein cholesterolSubtilisin kexin type 9Cardiovascular event reductionHard cardiovascular eventsHard cardiovascular outcomesPlacebo-controlled dataPrimary prevention patientsCardiovascular event ratesLDL-C reductionProportion of patientsClinical trial programLDL-C levelsIncidence rate ratios
2017
Cardiovascular Efficacy and Safety of Bococizumab in High-Risk Patients
Ridker PM, Revkin J, Amarenco P, Brunell R, Curto M, Civeira F, Flather M, Glynn RJ, Gregoire J, Jukema JW, Karpov Y, Kastelein JJP, Koenig W, Lorenzatti A, Manga P, Masiukiewicz U, Miller M, Mosterd A, Murin J, Nicolau JC, Nissen S, Ponikowski P, Santos RD, Schwartz PF, Soran H, White H, Wright RS, Vrablik M, Yunis C, Shear CL, Tardif JC. Cardiovascular Efficacy and Safety of Bococizumab in High-Risk Patients. New England Journal Of Medicine 2017, 376: 1527-1539. PMID: 28304242, DOI: 10.1056/nejmoa1701488.Peer-Reviewed Original ResearchMeSH KeywordsAntibodiesAntibodies, Monoclonal, HumanizedAnticholesteremic AgentsCardiovascular DiseasesCholesterol, LDLDouble-Blind MethodFemaleFollow-Up StudiesHumansHypercholesterolemiaInjections, SubcutaneousLipidsMaleMiddle AgedPCSK9 InhibitorsProprotein Convertase 9Risk FactorsTreatment FailureConceptsMajor cardiovascular eventsPrimary end pointHigh-risk patientsLDL cholesterol levelsCardiovascular eventsPlacebo groupCholesterol levelsMajor adverse cardiovascular eventsLow-density lipoprotein cholesterolEnd pointSubtilisin kexin type 9Safety of bococizumabAdverse cardiovascular eventsHigh cardiovascular riskNonfatal myocardial infarctionLow-risk patientsInjection site reactionsHumanized monoclonal antibodyDifferent entry criteriaLonger duration trialsShort-duration trialsCardiovascular efficacyNonfatal strokeUrgent revascularizationCardiovascular deathLipid-Reduction Variability and Antidrug-Antibody Formation with Bococizumab
Ridker PM, Tardif JC, Amarenco P, Duggan W, Glynn RJ, Jukema JW, Kastelein JJP, Kim AM, Koenig W, Nissen S, Revkin J, Rose LM, Santos RD, Schwartz PF, Shear CL, Yunis C. Lipid-Reduction Variability and Antidrug-Antibody Formation with Bococizumab. New England Journal Of Medicine 2017, 376: 1517-1526. PMID: 28304227, DOI: 10.1056/nejmoa1614062.Peer-Reviewed Original ResearchConceptsLDL cholesterol levelsProprotein convertase subtilisin kexin type 9Antidrug antibodiesCholesterol levelsLipoprotein cholesterolLow-density lipoprotein cholesterolSubtilisin kexin type 9Antidrug antibody formationLipid-lowering trialsCommon adverse eventsMajor cardiovascular eventsDensity lipoprotein cholesterolInjection site reactionsTime of enrollmentHumanized monoclonal antibodyCardiovascular eventsStatin therapyAdverse eventsTotal cholesterolMultinational trialTreatment periodBococizumabApolipoprotein BPatientsType 9
2016
Evaluating bococizumab, a monoclonal antibody to PCSK9, on lipid levels and clinical events in broad patient groups with and without prior cardiovascular events: Rationale and design of the Studies of PCSK9 Inhibition and the Reduction of vascular Events (SPIRE) Lipid Lowering and SPIRE Cardiovascular Outcomes Trials
Ridker PM, Amarenco P, Brunell R, Glynn RJ, Jukema JW, Kastelein JJ, Koenig W, Nissen S, Revkin J, Santos RD, Schwartz PF, Yunis C, Tardif JC, Investigators S. Evaluating bococizumab, a monoclonal antibody to PCSK9, on lipid levels and clinical events in broad patient groups with and without prior cardiovascular events: Rationale and design of the Studies of PCSK9 Inhibition and the Reduction of vascular Events (SPIRE) Lipid Lowering and SPIRE Cardiovascular Outcomes Trials. American Heart Journal 2016, 178: 135-144. PMID: 27502861, DOI: 10.1016/j.ahj.2016.05.010.Peer-Reviewed Original ResearchConceptsCardiovascular outcome trialsOutcome trialsCardiovascular eventsPatient groupAtherogenic lipidsCholesterol levelsHigh-risk primary preventionSubtilisin kexin type 9Hepatic low-density lipoprotein receptorMonoclonal antibodiesAtherogenic cholesterol levelsIncident vascular eventsResidual cholesterol riskSafety of bococizumabVascular event ratesHigh-risk patientsPrior cardiovascular eventsClinical cardiovascular eventsEvident cardiovascular diseaseLDL cholesterol levelsHigh-risk populationHumanized monoclonal antibodyLow-density lipoprotein receptorHigh residual riskBroad patient groups
2007
Effects of Torcetrapib in Patients at High Risk for Coronary Events
Barter PJ, Caulfield M, Eriksson M, Grundy SM, Kastelein JJ, Komajda M, Lopez-Sendon J, Mosca L, Tardif JC, Waters DD, Shear CL, Revkin JH, Buhr KA, Fisher MR, Tall AR, Brewer B. Effects of Torcetrapib in Patients at High Risk for Coronary Events. New England Journal Of Medicine 2007, 357: 2109-2122. PMID: 17984165, DOI: 10.1056/nejmoa0706628.Peer-Reviewed Original ResearchConceptsMajor cardiovascular eventsRisk of deathCardiovascular eventsCholesteryl ester transfer proteinLipoprotein cholesterolFirst major cardiovascular eventHigh-density lipoprotein cholesterolLow-density lipoprotein cholesterolEffects of torcetrapibHigh cardiovascular riskNonfatal myocardial infarctionDouble-blind studySystolic blood pressureCoronary heart diseaseRisk of mortalityPlasma lipoprotein levelsEster transfer proteinCoronary eventsCardiac eventsCardiovascular riskUnstable anginaBlood pressurePrimary outcomeSerum potassiumLipoprotein levelsTorcetrapib and carotid intima-media thickness in mixed dyslipidaemia (RADIANCE 2 study): a randomised, double-blind trial
Bots ML, Visseren FL, Evans GW, Riley WA, Revkin JH, Tegeler CH, Shear CL, Duggan WT, Vicari RM, Grobbee DE, Kastelein JJ, Investigators F. Torcetrapib and carotid intima-media thickness in mixed dyslipidaemia (RADIANCE 2 study): a randomised, double-blind trial. The Lancet 2007, 370: 153-160. PMID: 17630038, DOI: 10.1016/s0140-6736(07)61088-5.Peer-Reviewed Original ResearchConceptsIntima-media thicknessMaximum intima-media thicknessCarotid intima-media thicknessDouble-blind trialSystolic blood pressureCombined-treatment groupMixed dyslipidaemiaCholesteryl ester transfer proteinHDL cholesterolLipoprotein cholesterolBlood pressureLDL cholesterolCarotid segmentsHigh low-density lipoprotein cholesterolLow high-density lipoprotein cholesterolMaximum carotid intima-media thicknessHigh-density lipoprotein cholesterolLow-density lipoprotein cholesterolCarotid atherosclerosis progressionDose of treatmentYearly rateEster transfer proteinDose titrationPrimary endpointAtherosclerosis progressionEffect of Torcetrapib on the Progression of Coronary Atherosclerosis
Nissen SE, Tardif JC, Nicholls SJ, Revkin JH, Shear CL, Duggan WT, Ruzyllo W, Bachinsky WB, Lasala GP, Tuzcu EM. Effect of Torcetrapib on the Progression of Coronary Atherosclerosis. New England Journal Of Medicine 2007, 356: 1304-1316. PMID: 17387129, DOI: 10.1056/nejmoa070635.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAnticholesteremic AgentsAtorvastatinBlood PressureCardiovascular DiseasesCholesterol Ester Transfer ProteinsCholesterol, HDLCholesterol, LDLCoronary Artery DiseaseDisease ProgressionDouble-Blind MethodDrug Therapy, CombinationFemaleHeptanoic AcidsHumansMaleMiddle AgedProspective StudiesPyrrolesQuinolinesUltrasonography, InterventionalConceptsAtheroma volumeHDL cholesterolLDL cholesterolAtorvastatin monotherapyCoronary atherosclerosisLipoprotein cholesterolBlood pressureIntravascular ultrasonographyHigh-density lipoprotein cholesterolLow-density lipoprotein cholesterolEffects of torcetrapibCholesteryl ester transfer protein inhibitorsPercent atheroma volumeSystolic blood pressureHDL cholesterol levelsLack of efficacyCETP inhibitor torcetrapibMechanism of actionCardiovascular riskSmall favorable effectCholesterol levelsDisease progressionDiseased vessel segmentDrug classesSecondary measuresEffect of Torcetrapib on Carotid Atherosclerosis in Familial Hypercholesterolemia
Kastelein JJ, van Leuven SI, Burgess L, Evans GW, Kuivenhoven JA, Barter PJ, Revkin JH, Grobbee DE, Riley WA, Shear CL, Duggan WT, Bots ML. Effect of Torcetrapib on Carotid Atherosclerosis in Familial Hypercholesterolemia. New England Journal Of Medicine 2007, 356: 1620-1630. PMID: 17387131, DOI: 10.1056/nejmoa071359.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnticholesteremic AgentsAtherosclerosisAtorvastatinCarotid ArteriesCarotid Artery DiseasesCholesterol Ester Transfer ProteinsCholesterol, HDLCholesterol, LDLDisease ProgressionDouble-Blind MethodDrug Therapy, CombinationFemaleHeptanoic AcidsHeterozygoteHumansHyperlipoproteinemia Type IIMaleMiddle AgedProspective StudiesPyrrolesQuinolinesConceptsCarotid intima-media thicknessIntima-media thicknessHDL cholesterol levelsCholesterol levelsFamilial hypercholesterolemiaMean low-density lipoprotein cholesterol levelLow-density lipoprotein cholesterol levelsMean carotid intima-media thicknessMaximum carotid intima-media thicknessAverage systolic blood pressureMean HDL cholesterol levelHigh-density lipoprotein cholesterolCarotid arterial wall thicknessCommon carotid segmentEffects of torcetrapibSecondary efficacy measuresLipoprotein cholesterol levelsSystolic blood pressureAtherosclerotic vascular diseaseCommon carotid arteryB-mode ultrasonographyProgression of diseaseArterial wall thicknessCholesteryl ester transfer proteinEster transfer proteinDesigns of RADIANCE 1 and 2:carotid ultrasound studies comparing the effects of torcetrapib/atorvastatin with atorvastatin alone on atherosclerosis*
Kastelein JJ, van Leuven SI, Evans GW, Riley WA, Revkin JH, Shear CL, Bots ML. Designs of RADIANCE 1 and 2:carotid ultrasound studies comparing the effects of torcetrapib/atorvastatin with atorvastatin alone on atherosclerosis*. Current Medical Research And Opinion 2007, 23: 885-894. PMID: 17407645, DOI: 10.1185/030079907x182121.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedAlgorithmsAnticholesteremic AgentsAtherosclerosisAtorvastatinCarotid ArteriesClinical Trials as TopicDouble-Blind MethodDrug Therapy, CombinationFemaleHeptanoic AcidsHumansHyperlipidemia, Familial CombinedHyperlipoproteinemia Type IIMaleMiddle AgedModels, BiologicalPyrrolesQuinolinesResearch DesignTunica IntimaUltrasonographyConceptsCarotid intima-media thicknessMaximum carotid intima-media thicknessNCEP ATP III guidelinesATP III guidelinesCarotid ultrasound studiesDose of atorvastatinPrimary efficacy measureLDL-C levelsIntima-media thicknessHeterozygous familial hypercholesterolemiaEnd of studyB-mode ultrasonographyFurther outcome measuresRADIANCE studyEligible subjectsControlled TrialsAtherosclerotic progressionEfficacy measuresMixed hyperlipidemiaTreatment periodOutcome measuresUltrasound studyNumber of subjectsFamilial hypercholesterolemiaCarotid segments