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
Lipid-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 9Cardiovascular 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 death
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 levelsBiomarkers in the Prevention and Treatment of Atherosclerosis: Need, Validation, and Future
Revkin JH, Shear CL, Pouleur HG, Ryder SW, Orloff DG. Biomarkers in the Prevention and Treatment of Atherosclerosis: Need, Validation, and Future. Pharmacological Reviews 2007, 59: 40-53. PMID: 17329547, DOI: 10.1124/pr.59.1.1.Peer-Reviewed Original ResearchConceptsAtherosclerotic progressionClinical trialsCardiovascular diseaseCardiovascular outcomesSurrogate markerCarotid intima-media thicknessIdeal surrogate markerFuture cardiovascular eventsIntima-media thicknessCause of morbidityNew cardiovascular drugsQuantitative coronary angiographyTreatment of atherosclerosisNovel therapeutic strategiesB-mode ultrasoundAtheroma volumeCardiovascular eventsCardiovascular riskCoronary angiographyEffective therapySurrogate endpointsCardiovascular drugsTherapeutic strategiesIntravascular ultrasoundSuch trials