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RESEARCH PRODUCT
Vorapaxar in the secondary prevention of atherothrombotic events
Jose NicolauAndrzej RynkiewiczKeith FoxVahid MansouriFausto Miranda JuniorJose Antônio Marin-netoCarlos TauilYves SamsonGiovanni EspositoDavid MorrowWojciech SobiczewskiJames SprattJacek KubicaMiguel UrinaStefano CarugoMajken Karoline JensenFrans Van De WerfStavros KonstantinidesOscar Ayo-martinLucia MazzolaiIsabella TrittoEric Hernandez-trianaPhilip BathDiana GorogGraeme J. HankeyJuhani AiraksinenMarco VatranoJose Faria NetoPeter SinnaeveRoman HerzigSerge TimsitUrszula FiszerAttila CsányiMarcia ChavesRobert MikulikMarek RoikMónica JaramilloMichel GalinierHelle Klingenberg IversenBassem A. SamadPhilippe Gabriel StegElizabeth CoetseeGuillermo IsastiDomenico ScrutinioSilvia Reverté VillarroyaMalcolm Robert MacleodMichael LimAmos KatzMeyer ElbazDerek ChewHanne ChristensenMarkus TheurlSimona MarcheselliPatricia SimalMichal BarIsabelle QuéréGeert VanhoorenPiotr PonikowskiXavier Garcia-mollElena CorradaRobert WelshHelge WuttigPhilip AylwardCarl Magnus WahlgrenMarco Stramba-badialeFernando ManzurLaurent SuissaThierry MoulinGiancarlo MarenziGian Battista DanziBogumił RamotowskiCaitrin McdonoughAfanasiev StanislavRaul Carlos ReyEmilia Solinassubject
MalePyridines[SDV]Life Sciences [q-bio]Myocardial InfarctionMedizinKaplan-Meier Estimate030204 cardiovascular system & hematologyBrain IschemiaLactones0302 clinical medicineMESH: Peripheral Arterial DiseaseSecondary PreventionMESH: Double-Blind Method030212 general & internal medicineMyocardial infarctionStrokeVorapaxarMESH: AgedAspirinMESH: Middle AgedMESH: RiskCardiovascular diseases [NCEBP 14]MESH: Secondary PreventionHazard ratioMESH: Brain IschemiaGeneral MedicineMiddle AgedClopidogrel3. Good healthStrokeMESH: Receptor PAR-1MESH: Myocardial Infarctionvorapaxar secondary prevention atherothrombotic eventsCardiovascular DiseasesMESH: Platelet Aggregation InhibitorsAnesthesiaRetreatmentPlatelet aggregation inhibitorFemaleIntracranial HemorrhagesMESH: HemorrhageMESH: Intracranial HemorrhagesMESH: Lactonescirculatory and respiratory physiologymedicine.drugRiskISQUEMIA CEREBRALHemorrhagePlaceboMESH: StrokePeripheral Arterial Disease03 medical and health sciencesDouble-Blind Method[INFO.INFO-IM]Computer Science [cs]/Medical ImagingmedicineHumansReceptor PAR-1MESH: RetreatmentMESH: Kaplan-Meier EstimateAgedMESH: Humansbusiness.industryMESH: PyridinesMESH: Cardiovascular Diseasesmedicine.diseaseSettore MED/11 - Malattie Dell'Apparato CardiovascolareMESH: MalebusinessMESH: FemalePlatelet Aggregation Inhibitorsdescription
BACKGROUND: Thrombin potently activates platelets through the protease-activated receptor PAR-1. Vorapaxar is a novel antiplatelet agent that selectively inhibits the cellular actions of thrombin through antagonism of PAR-1. METHODS: We randomly assigned 26,449 patients who had a history of myocardial infarction, ischemic stroke, or peripheral arterial disease to receive vorapaxar (2.5 mg daily) or matching placebo and followed them for a median of 30 months. The primary efficacy end point was the composite of death from cardiovascular causes, myocardial infarction, or stroke. After 2 years, the data and safety monitoring board recommended discontinuation of the study treatment in patients with a history of stroke owing to the risk of intracranial hemorrhage. RESULTS:At 3 years, the primary end point had occurred in 1028 patients (9.3%) in the vorapaxar group and in 1176 patients (10.5%) in the placebo group (hazard ratio for the vorapaxar group, 0.87; 95% confidence interval [CI], 0.80 to 0.94; P<0.001). Cardiovascular death, myocardial infarction, stroke, or recurrent ischemia leading to revascularization occurred in 1259 patients (11.2%) in the vorapaxar group and 1417 patients (12.4%) in the placebo group (hazard ratio, 0.88; 95% CI, 0.82 to 0.95; P = 0.001). Moderate or severe bleeding occurred in 4.2% of patients who received vorapaxar and 2.5% of those who received placebo (hazard ratio, 1.66; 95% CI, 1.43 to 1.93; P<0.001). There was an increase in the rate of intracranial hemorrhage in the vorapaxar group (1.0%, vs. 0.5% in the placebo group; P<0.001). CONCLUSIONS:Inhibition of PAR-1 with vorapaxar reduced the risk of cardiovascular death or ischemic events in patients with stable atherosclerosis who were receiving standard therapy. However, it increased the risk of moderate or severe bleeding, including intracranial hemorrhage. (Funded by Merck; TRA 2P-TIMI 50 ClinicalTrials.gov number, NCT00526474.) Copyright © 2012 Massachusetts Medical Society.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2012-04-12 |