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Introduzione all’importanza della doppia antiaggregazione e del raggiungimento dei target

Introduzione all’importanza della doppia antiaggregazione e del raggiungimento dei target Cesare Greco. Le modificazioni dell’epidemiologia e le difficoltà dalla prevenzione secondaria. Mortality composition at 5 years follow up . 100%. 97%. 86%. 68%. In-H. Post-H.

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Introduzione all’importanza della doppia antiaggregazione e del raggiungimento dei target

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  1. Introduzione all’importanza della doppia antiaggregazione e del raggiungimento dei target Cesare Greco

  2. Le modificazioni dell’epidemiologia e le difficoltà dalla prevenzione secondaria

  3. Mortalitycomposition at 5 yearsfollow up 100% 97% 86% 68% In-H Post-H STEMI NSTEMI UA Fox Eur Heart J 2010

  4. Fox Eur Heart J 2010

  5. Registro IN-ACS Outcome Mortalità intraospedaliera e ad 1 anno: SCA-NSTE e STEMI 15% STEMI 9.8% SCA NSTE 8.6% 10% X 4 X 2 5% 4.4% 2 % In-H Dimissione 1 anno Rizzello Acute Card Care 2012

  6. Registro IN-ACS Outcome Reinfarto dalla dimissione ad 1 anno: SCA-NSTE e STEMI 10% STEMI 5.4 % SCA NSTE 4.3% 5% Rizzello Acute Card Care 2012

  7. Registro IN-ACS Outcome Sottoutilizzo dei trattamenti raccomandati alla dimissione negli STEMI ad alto rischio (non riperfusi) STEMI Non riperfusiSTEMI PCI STEMI Trombolisi Antiaggreganti 93% 99% 96% Doppia 58% 94% 63% antiaggregazione Betabloccanti 71% 83% 75% Statine 68% 78% 77% P<0.0001 per tutti Pedone Acute Card Care 2009

  8. Total mortality at 6 months follow up STEMI x 2 NSTEMI x4 Discharge-30 days 30 days-6 months

  9. BLITZ4 Performance of CCU Adherence to pharmacological therapy Discharge 6 months 11.706 AMI patients from 163 Coronary Units

  10. BLITZ4 Performance of Centers Process of care In-Hospital indicators LV function assessment LDL measurement Risk stratification Post-discharge indicators Anti smoke counseling Cardiac rehabilitation referral

  11. 30 day and 31–365 daymortalityafter first timehospitalisation formyocardialinfarctionbetween 1984 and 2008 in a Danishnationwidecohortstudy Schmidt et al. BMJ 2012

  12. Kostis Circ Cardiovasc Qual Outcomes 2010

  13. Therapeutic Control of Blood Pressure* P=0.57 S2 vs. S1 : P=0.98 S3 vs. S2 : P=0.36 S3 vs. S1 : P=0.37 * SBP/DBP < 140/90 mmHg for non-diabetics or < 130/80 mmHg for diabetics The EUROASPIRE Surveys

  14. Prevalence of Diabetes* P=0.004 * Self-reported history of diagnosed diabetes S2 vs. S1 : P=0.21 S3 vs. S2 : P=0.02 S3 vs. S1 : P=0.001 The EUROASPIRE Surveys

  15. Prevalence of Smoking* P=0.64 * Self-reported smoking or CO in breath > 10 ppm S2 vs. S1 : P=0.83 S3 vs. S2 : P=0.37 S3 vs. S1 : P=0.48 The EUROASPIRE Surveys

  16. DAT administered prior to acute coronary syndrome (ACS) event, at hospital discharge, and at 6- and 12-months Zeymer Eur J Prev Cardiol 2012

  17. Aderenza, tollerabilità ed efficacia

  18. Interruzione dei trattamenti raccomandati durante il follow-up in pazienti con Pregresso IMA Dati del registro SIMG - HealthSearch - JCVM 2009 100% 80% 60% 40% 20% 0% 1 anno 2 anni 3 anni 4 anni 5 anni ASA Beta-B Statine ACE/ARB

  19. L’Interruzione precoce delle terapie farmacologiche basate sull’evidenza dopo una SCA è molto frequente I dati del Registro PREMIER Predittori indipendenti di interruzione della terapia • Età avanzata (≥70 anni) • Basso livello socio-economico • Sesso femminile • Mancata effettuazione di PTCA durante il ricovero • Presenza di patologie maggiori concomitanti 1521 pazienti dimessi dopo IMA Ho PM,et al Arch. Int. Med. 2006

  20. Ho et al. ArchInternMed. 2006;166:1842-1847

  21. Eur Heart J 2008

  22. Spertus Circulation 2006

  23. 14,007 patientsadmittedforMI in the first hal f of 2006 Tuppin Arch Cardiovasc Dis 2010

  24. Osservatorio ARNO CardiovascolareLa prevenzione secondaria dopo un evento di Sindrome Coronarica Acuta http://osservatorioarno.cineca.org

  25. Osservatorio ARNO CardiovascolareLa prevenzione secondaria dopo un evento di Sindrome Coronarica Acuta http://osservatorioarno.cineca.org

  26. Osservatorio ARNO CardiovascolareLa prevenzione secondaria dopo un evento di Sindrome Coronarica Acuta http://osservatorioarno.cineca.org

  27. Osservatorio ARNO CardiovascolareLa prevenzione secondaria dopo un evento di Sindrome Coronarica Acuta http://osservatorioarno.cineca.org

  28. Osservatorio ARNO CardiovascolareLa prevenzione secondaria dopo un evento di Sindrome Coronarica Acuta http://osservatorioarno.cineca.org

  29. Osservatorio ARNO CardiovascolareLa prevenzione secondaria dopo un evento di Sindrome Coronarica Acuta http://osservatorioarno.cineca.org

  30. Aderenza, tollerabilità ed efficacia

  31. Patrono N Engl J Med 2011 Patrono et al. for ESC Task Force Eur Heart J 2004

  32. The risk for serious GI bleeding with low-dose ASA is continuous (VALIANT trial) Dotted lines: 95% CIs of the estimated rate Moukarbel Eur Heart J 2009 ASA = acetylsalicylic acid; CI = confidence interval; GI = gastrointestinal

  33. Aspirin leads to suppression of mucosal prostaglandin synthesis and subsequent formation of mucosal erosions Whereas the inhibition of thromboxane-A2-mediated platelet function is dose independent (at least for daily doses N30 mg), the impairment of PGE2-mediated cytoprotection in the GI mucosa is dose dependent Patrono et al. for ESC Task Force Eur Heart J 2004

  34. ASA therapy increases the odds of upperGI bleeding Low-dose ASA ASA = acetylsalicylic acid; GI = gastrointestinal; NSAIDs = non-steroidal anti-inflammatory drugs.*non-ASA NSAID; **any dose, for less than 1 month Weil et al. BMJ 1995

  35. Alternative ASA formulations do not reduce the relative risk of upper GI bleeding ASA dose ≤ 325 mg/day Kelly et al. Lancet 1996

  36. (75 or 81) Primary efficacy end point (CV death, myocardial infarction, or stroke) Steinhubl for CHARISMA Ann Int Med 2009

  37. Effects of Aspirin Dose When Used Alone or in Combination With Clopidogrel in Patients With Acute Coronary Syndromes: the CURE Study Aspirin dose and the incidence of major bleeding *Adjusted for gender, weight, hypertension, components of the TIMI risk score, rates of angiography, PCI and CABG, and the use of NSAIDs, heparin, GP2B3A inhibitors, oral anticoagulants, open-label ticlopidine, or clopidogrel at any time during the study period Peters Circulation 2003

  38. Risk of upper GI bleed among low-dose ASA users is reduced by proton pump inhibitor (PPI) use 2049 cases of upper GI bleed; 20 000 controls (The Health Improvement Network UK primary care database) Current use of PPI for >30 days reduced the risk of upper GI bleed in low-dose ASA users and other at-risk groups Lin Gastroenterology 2011

  39. GI problems reported by patients taking low-dose ASA for CV risk management Moberg C et al. The Patient 2011

  40. ASTERIX randomized study: ulcer incidence 26 weeks 71% reduction inulcer occurrence p=0.0007 Esomeprazole 20 mg Placebo Yeomans Am J Gastroenterol 2008

  41. ASTERIX study: resolution of upper GI symptoms from aspirin* *Analysis concerns patients with resolution of investigator-assessed upper GI symptoms at 26 weeks, among patients with the symptom at baseline Yeomans Am J Gastroenterol 2008

  42. 25 20 15 10 5 0 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0 Low-dose ASA alone Low-dose ASA + esomeprazole Esomeprazole alone Esomeprazole + low-dose ASA Concentration (mmol/L) Concentration (mmol/L) 0 1 2 3 4 5 6 0 2 4 6 8 10 12 Time (hours) Time (hours) Lack of pharmacokinetic interaction between esomeprazole and low-dose ASA Arithmetic mean plasma concentration–time profiles of ASA (325 mg) and esomeprazole (40 mg) following 5 days’ repeated oral administration, alone and in combination Niazi Int J Clin Pharmacol Ther 2009 ASA = acetylsalicylic acid

  43. Aderenza, tollerabilità ed efficacia

  44. Perk Eur Heart J 2012

  45. Incidenza di eventi in funzione dei livelli di C-LDL raggiunti nei trial con statine 30 4S - Placebo 25 Rx - Statintherapy PRA – pravastatin ATV - atorvastatin Prevenzione Secondaria 4S - Rx 20 LIPID - Placebo 15 Incidenza di eventi (%) CARE - Placebo LIPID - Rx CARE - Rx Prevenzione Primaria HPS - Placebo TNT – ATV10 HPS - Rx 10 PROVE-IT - PRA WOSCOPS – Placebo TNT – ATV80 AFCAPS - Placebo 6 5 AFCAPS - Rx WOSCOPS - Rx ASCOT - Placebo JUPITER - Placebo JUPITER - Rx ASCOT - Rx 0 40 (1.0) 60 (1.6) 80 (2.1) 100 (2.6) 120 (3.1) 140 (3.6) 160 (4.1) 180 (4.7) 200 (5.2) LDL-C, livelli raggiunti, mg/dL (mmol/L)

  46. Riduzione percentuale del C-LDL in funzionedella dose delle statine (mg) Studio STELLAR 10 20 40 80 0 Riduzione media della colesterolemia LDL ottenuta con rosuvastatina rispetto alle altre statine -10 +26% -20 +17% Variazione del colesterolo LDL (%) vs. basale Pravastatina(n=485) -30 +8% Simvastatina(n=648) -40 Atorvastatina(634) -50 * Rosuvastatina(n=473) † ‡ -60 *p<0,002 vs Atorvastatina 10 mg; Simvastatina 10, 20, 40 mg; Pravastatina10, 20, 40 mg †p<0,002 vs Atorvastatina 20, 40 mg; Simvastatina 20, 40, 80 mg; Pravastatina 20, 40 mg ‡p<0,002 vs Atorvastatina 40 mg; Simvastatina 40, 80 mg; Pravastatina 40 mg Jones PH et al. Am J Cardiol 2003;92:152-160

  47. LUNAR(Limiting UNder-treatment of lipids in ACS with Rosuvastatin) Atorvastatin80 mg Rosuvastatin40 mg Rosuvastatin20 mg Average change in LDL-C from baseline (%) * Primary Endpoint *p< 0.05 versus atorvastatin 80 mg Similar results were achieved in all subcategories of ACS Pitt B et al. Am J Cardiol 2012

  48. LUNARSecondary Endpoint *** ** Mean change in HDL-C from baseline (%) Atorvastatin80 mg Rosuvastatin40 mg Rosuvastatin20 mg **p< 0.01, *** p<0.001 versus atorvastatin 80 mg Pitt B et al. Am J Cardiol 2012

  49. LUNARSafety & Tolerability *None of the serious adverse effects (AEs), serious cardiovascular AEs or deaths were considered by the investigators to be related to study treatment Pitt B et al. Am J Cardiol 2012

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