Luigi Oltrona Visconti Divisione di Cardiologia IRCCS Fondazione Policlinico S. Matteo Pavia

Click here to load reader

  • date post

    12-Jan-2016
  • Category

    Documents

  • view

    59
  • download

    0

Embed Size (px)

description

HEARTLINE 2014 IRCCS S. Martino Genoa Cardiology Meeting. SCA-NSTEMI Trattamento antipiastrinico ed eccesso di sanguinamento : dove portano i risultati dell’ ACCOAST ?. Luigi Oltrona Visconti Divisione di Cardiologia IRCCS Fondazione Policlinico S. Matteo Pavia. 2011. - PowerPoint PPT Presentation

Transcript of Luigi Oltrona Visconti Divisione di Cardiologia IRCCS Fondazione Policlinico S. Matteo Pavia

  • Luigi Oltrona ViscontiDivisione di CardiologiaIRCCS Fondazione Policlinico S. MatteoPavia HEARTLINE 2014IRCCS S. MartinoGenoa Cardiology MeetingSCA-NSTEMITrattamento antipiastrinico ed eccesso di sanguinamento : dove portano i risultati dell ACCOAST ?

  • 2011

  • PCI-CURE Principali risultati

  • PCI-CURE - Disegno dello studio (2) * La terapia in aperto comprendeva un antagonista del recettore dell'ADP in associazione a ASA La terapia tradizionale comprendeva sempre ASA, e poteva anche includere eparina, LMWH, inibitori della GP IIa/IIIb post randomizzazione, beta-bloccanti, ACE inibitori, ipolipidemizzanti e/o altre terapie o interventi (ad es. PTCA, CABG), a discrezione del medico LMWH, eparina a basso peso molecolare; GP, glicoproteina; PTCA, angioplastica coronarica transluminale percutanea; CABG, bypass coronarico The CURE Investigators. N Eng J Med August 2001PCIMesi 12Clopidogrel 75 mg/die + terapia tradizionale (n=1313) Placebo 1 cpr/die +terapia tradizionale (n=1345)PCI = Intervento coronarico percutaneo Giorno 30 Tienopiridina +ASA in aperto*per 2-4 settimane Mesi 12Giorno 30

  • *On top of standard therapy (including ASA)PCI-CURE: 31% Riduzione del Rischio Relativo a Lungo Termine11. Mehtra SR et al. Lancet 2001; 358: 52733. Endpoint: Infarto Miocardico o Morte Cardiovascolare

  • The CREDO TrialClopidogrel for the Reduction of EventsDuring Observation

  • Disegno dello studio Braccio ClopidogrelBraccio PlaceboPCI28 GiorniLD Placebo# Pre-trattaentoLD Clopidogrel#Clopidogrel#Clopidogrel#LD=dose di carco, PT= Pre-trattamento, R= Randomizzatzione# in aggiunta alla terapia standard comprendente ASA (325 mg)in aggiunta alla terapia standard comprendente ASA (81-325 mg)RClopidogrel*Placebo*12 MesiSteinhubl S, et al. JAMA, November 20, 2002 Vol 288, No 19: 2411 2420

  • Precoce effetto del pretrattamento con Clopidogrel: risultati Per Protocollo

    18.5 % RRRp = 0.23*Dal PCI sino al 28 giorno, In aggiunta alla terapia standard comprendente ASA (325mg dalla randomizzazione al 28 giorno) PT= Pre-trattamento UTVR: Target Vessel Revascularization UrgenteGIORNI DALLA RANDOMIZZAZIONE07142128PT con Clopidogrel*Senza PT con Clopidogrel*6.8%8.3%(Morte, IM e TVR urgente)Risultati a 28 giorniSteinhubl S, et al. JAMA, November 20, 2002 Vol 288, No 19: 2411 2420COMPARSA DELL ENDPOINT COMPOSITO (%)

  • Momento della dose di carico risultato a 28 giorniHazard ratio (95% CI) < 6 hrs 7.9 7.0893 6 to 24 hr 5.8 9.4 851 RRR -13.4p=NSRRR 38.6 p=0.05RRR 18.5p=0.23Risultati globali dello studio CREDOn PT-Clopidogrel*Senza-PT Clopidogrel*Eventi (%)Senza-PT ClopidogrelmigliorePT-Clopidogrelmigliore* In aggiunta alla terapia standard comprendente ASA, PT= Pre-trattamento Steinhubl S, et al. JAMA, November 20, 2002 Vol 288, No 19: 2411 2420

  • Study DesignDouble-blindACS (STEMI or UA/NSTEMI) & Planned PCIASAPRASUGREL60 mg LD/ 10 mg MDCLOPIDOGREL300 mg LD/ 75 mg MD1o endpoint: CV death, MI, Stroke2o endpoints:CV death, MI, Stroke, Rehosp-Rec IschCV death, MI, UTVR Stent Thrombosis (ARC definite/prob.) Safety endpoints: TIMI major bleeds, Life-threatening bleeds Key Substudies:Pharmacokinetic, GenomicMedian duration of therapy - 12 monthsN= 13,600Nuovi antiaggreganti orali : prasugrel evidenze cliniche di efficacia

  • 0510150306090180270360450HR 0.81 (0.73-0.90) P=0.0004Prasugrel ClopidogrelHR 0.80 P=0.0003HR 0.77 P=0.0001Days Primary Endpoint (%)12.1 (781)9.9 (643)Primary Endpoint CV Death,MI,StrokeNNT= 46ITT= 13,608LTFU = 14 (0.1%)Nuovi antiaggreganti orali : prasugrel evidenze cliniche di efficacia

  • A Comparison of Prasugrel at the Time of Percutaneous Coronary Intervention Or as Pre-treatment At the Time of Diagnosis in Patients with Non-ST-Elevation Myocardial Infarction (NSTEMI)

  • ACCOAST Trial designPrasugrel 30 mgPrasugrel 60 mg Prasugrel 30 mg Prasugrel 10 mg or 5 mg (based on weight and age) for 30 daysPCI1 Endpoint: CV Death, MI, Stroke, Urg Revascularization, GP IIb/IIIa bailout at 7 days

    Placebo

    CoronaryAngiographyn~4100 (event driven)CoronaryAngiographyPCICABG orMedicalManagement(no prasugrel) CABG orMedicalManagement(no more prasugrel)Montalescot G et al. Am Heart J 2011;161:650-656Randomize 1:1Double-blindNSTEMI + Troponin 1.5 times ULN local lab valueClopidogrel naive or on long term clopidogrel 75 mg

  • NEJM 2013;369:999-1010

  • To answer the question:IN NSTEMI patients, does having good inhibition of P2Y12 mediated platelet activation and aggregation prior to the start of PCI reduce the incidence of ischemic events compared to administration of a fast acting inhibitor (prasugrel) on the table?Potential benefits of pretreatment:Prevention of ischemic events in NSTEMI patients while waiting for the PCI, during and after PCI. Potential risks of pretreatment:Bleeding risks need to be considered when starting platelet inhibition in NSTEMI patients before the coronary anatomy is known (eg, the patient will not be a candidate for PCI- medical management or CABG). Clinical questions and rationale of the study

  • Enrollment: >4,000 patients in 19 Countries

    Latvia: 5Montalescot et al. NEJM 2013; epub Sept 1

  • Toni Badia, Ospedale Misericordia e Dolce, Prato; Sergio Berti, Fondazione Toscana G. Monasterio -Ospedale del Cuore G. Pasquinucci, Massa; Leonardo Bolognese, Cardiovascular and Neurological Department Azienda Ospedaliera Arezzo; Francesco Maria Bovenzi, Ospedale Campo di Marte, Lucca; Paola Camisasca,Nuovo Ospedale San Gerardo, Monza, Milano; Claudio Cavallini, Ospedale Santa Maria della Misericordia,Perugia; Raffaele De Caterina, Ospedale SS. Annunziata, Chieti; Stefano De Servi, Ospedale di Legnano, Legnano,Milano; Giuseppe Fantini, Policlinico Universitario Modena, Modena; Claudio Fresco, Azienda Ospedaliero Universitaria Santa Maria della Misericordia, Udine; Antonio Manari, Azienda Ospedaliera-IRCCS S. Maria Nuova, Reggio Emilia; Sebastiano Marra, Azienda Ospedaliera S.Giovanni Battista, Torino; Ciro Mauro, AziendaOspedaliera Antonio Cardarelli, Napoli; Luca Olivotti, Ospedale Santa Corona, Pietra Ligure; Anna Sonia Petronio, Stabilimento Ospedaliero di Cisanello, Pisa; Francesco Prati, S. Giovanni Hospital, Rome; Bernhard Reimers, Ospedale Civile di Mirano, Venezia; Massimo Santini, Ospedale S. Filippo Neri, Roma; Silva Severi, Ospedale Misericordia, Grosseto; Luigi Oltrona Visconti, Division of Cardiology, Fondazione IRCCS Policlinico San Matteo, Pavia; Corrado Tamburino, Ospedale Ferrarotto, Catania; Roberto Zanini, Ospedale Civile Carlo Poma, Mantova.

  • Main Inclusion/Exclusion CriteriaInclusionNSTEMI symptoms within 48 hours prior to study entry Elevated troponin (1.5 times ULN) per local lab(s)Patient to be scheduled for coronary angiography and PCI within 2 hours to 24 hours of randomization and no later than 48 hours after randomization

    ExclusionSTEMI patientsMedical history contraindicating therapy with prasugrel History of stroke or transient ischemic attack (TIA)LD of any P2Y12 antagonist 7days of study entry

    Montalescot G et al. Am Heart J 2011;161:650-656.e1

  • Patient DispositionPre-treatmentN=2037 Lost to Follow-up 1 (0.05)ITT and All TreatedN= 4033Total RandomizedN=4038 Day 30 Visit N=1958 (96.12%)Day 7N=2009 (98.63%)No Pre-treatmentN=1996Lost to Follow-up 2 (0.10)Day 30 VisitN=1924 (96.39%) Day 7N=1964 (98.40%)Montalescot et al. NEJM 2013; epub Sept 1

  • Baseline CharacteristicsMontalescot et al. NEJM 2013; epub Sept 1

    CharacteristicsPre-treatment(N =2037)No Pre-treatment(N =1996)Age (mean, yrs)63.863.6Female sex (%)27.128.0Weight (mean, kg)81.781.5BMI 30 (%)29.028.2CV risk factors (%) Diabetes mellitus20.320.4 Dyslipidemia44.945.1 Hypertension62.861.4 Current smoker34.132.5Region of enrolment (%) Eastern Europe/Israel42.441.5 Western Europe/Canada57.658.5

  • Baseline CharacteristicsMontalescot et al. NEJM 2013; epub Sept 1

    CharacteristicsPre-treatment(N =2037)No Pre-treatment(N =1996)GRACE score (%)

  • Baseline Characteristics*Monotherapy is reported; N=1323 for pre-treatment and N=1275 for no pre-treatment **75-mg dose allowed per the protocolMontalescot et al. NEJM 2013; epub Sept 1

    Concomitant medications through 7 days (%)Pre-treatment(N =2037)No Pre-treatment(N =1996)Aspirin, (%)98.298.0Antithrombin Use, (%)*UFH65.465.5LMWH29.130.6Bivalirudin0.80.6Fondaparinux4.73.3Proton pump inhibitor54.855.8Beta blockers84.484.3Statins89.589.5ARBs13.712.0ACE inhibitors 69.071.8Calcium channel blockers29.927.3On a MD of clopidogrel at randomization**2.22.2

  • Efficacy Results

  • 1 Efficacy End Point @ 7 + 30 days (All Patients) Montalescot et al. NEJM 2013; epub Sept 1

  • Secondary Efficacy Endpoint of CV Death, MI, Stroke (All Patients)Montalescot et al. NEJM 2013; epub Sept 1

  • 1 Efficacy Endpoint (PCI Patients)Montalescot et al. NEJM 2013; epub Sept 1

  • Major Efficacy Endpoints Through 7 Days (All Patients)

    *Hazard ratio and two-sided 95% CI are from a Cox proportional hazards model with treatment as a fixed effect. Two-sided P-value based on the log rank test. Montalescot et al. NEJM 2013; epub Sept 1

    EndpointPre-treatment(n = 2037)No pre-treatment(n = 1996)HR*(95% CI)P-ValueCVD, MI, stroke, UR or GPIIb/IIIa bailout (primary endpoint)203 (10.0)195 (9.8)1.02 (0.84, 1.25)0.81DeathAll cause8 (0.4)10 (0.5)0.78 (0.31, 1.98)0.61CV7 (0.3)10 (0.5) 0.69 (0.26, 1.80)0.44MI119 (5.8)109 (5.5)1.07 (0.83, 1.39)0.60Stroke8 (0.4)10 (0.5)0.78 (0.31, 1.98)0.60UR22 (1.1)26 (1.3)0.83 (0.47, 1.46)0.52GPIIb/IIIa bailout76 (3.7)78 (3.9)0.96 (0.70, 1.31)0.79

  • 1 Efficacy Endpoint Through 7 Days for Pre