Da quanto visto analizzando la letteratura scientifica attualmente disponibile,
la fibrinolisi extraospedaliera come strategia riperfusiva è sicura ed efficace,
permette considerevoli risparmi di tempo sulla fibrinolisi eseguita in ambito ospedaliero, e si rivela imprescindibile in quelle situazioni di “delay” rispetto alla procedura di angioplastica primaria.
Lo sviluppo di farmaci sempre più “user friendly”, sia per le modalità di som- ministrazione, sia per la farmacocinetica del prodotto, che per la selettività del
farmaco per il coagulo, permettono un uso della procedura fibrinolitica sicuro.
Tale uso è possibile sia nelle mani di medici opportunamente addestrati e pa- droni dell’arte, sia se adottato da personale paramedico qualificato; questa im- portante possibilità apre le porte a una maggiore e più capillare diffusione del-
la terapia trombolitica.
Nonostante i positivi risultati dei trial e delle metanalisi, la PPCI, eseguita da
team esperti in centri di alto livello, resta la scelta ottimale per la riperfusione nell’infarto STEMI; l’associazione delle due tecniche, nella modalità della PCI “facilitata”, “fast” e “rescue” si rivela un ottimo compromesso per quelle si- tuazioni in cui tempistiche di trasferimento particolarmente lunghe o impedi-
menti di ordine tecnico – logistico non permettono un rapido accesso presso il
laboratorio coronarografico.
Lo studio dell’associazione delle procedure riperfusive con farmaci antiaggre-
ganti piastrinici o antitrombotici ha portato notevoli risultati, soprattutto per quanto riguarda la PCI “facilitata” e la combinazione con la fibrinolisi extrao-
87
spedaliera, andando così ad aumentare le armi a disposizione del professioni- sta medico d’urgenza nell’approccio al paziente.
Le linee guida, in accordo con tali risultati scientifici, prevedono l’uso della fibrinolisi, anche extraospedaliera, all’interno degli “STEMI network” che le realtà territoriali dovrebbero adottare per l’approccio al paziente con IMA. La situazione Toscana, che per sua natura è varia sia come geografia sia come
densità di popolazione, mostra una buona aderenza alle linee guida internazio-
nali, ma una scarsa cultura della fibrinolisi: solo una ASL nel territorio tosca-
no ha avviato un progetto di sviluppo della procedura fibrinolitica extraospe-
daliera 90, mentre nelle altre si assiste ad un uso della trombolisi molto rarefat-
to. Questo può essere imputabile a una scarsa confidenza del personale medico
con tale proceduta, che possiede un effettivo rischio di complicanza emorragi-
ca, minimizzabile con la padronanza delle conoscenze circa la fisiopatologia
dello STEMI e un corretto uso dei più moderni farmaci a disposizione. Altro
fattore imputabile dello scarso uso di fibrinolitici può essere il costo di tali
farmaci, che per quanto estremamente efficaci, è molto alto, e di conseguenza
un altro motivo può essere ipotizzato nella volontà delle politiche economiche
aziendali di non destinare fondi così ingenti a programmi extraospedalieri, ge-
stiti in massima parte da ONLUS e privati, ma di usare tali fondi per potenzia-
re la risposta del sistema ospedaliero allo STEMI.
Punto dolente dei protocolli toscani per lo STEMI è la mancanza, in molti di
questi, della specifica di un controllo dei dati clinici: solo due ASL 89, 90 speci-
88
loro protocolli, mentre altre 86 identificano nell’audit clinico il sistema di con-
trollo del protocollo messo in atto.
La raccolta dei dati dei vari protocolli riguardanti mortalità, tempistiche, e struttura dei vari “STEMI network” territoriali dovrebbe quindi essere eseguita in modo da permettere un confronto tra le diverse realtà e tra approcci diversi
applicati nello stesso territorio, in un’ottica di miglioramento che dovrebbe es-
sere cardine della pratica medica.
Nello specifico, la diffusione capillare della fibrinolisi extraospedaliera sul ter-
ritorio Toscano può essere incoraggiata dallo sviluppo di studi mirati sia sulla
procedura stessa, sia in generale sulle strategie riperfusive, cardine imprescin-
89
BIBLIOGRAFIA:
1. DeWood MA, Spores J, Notske R, Mouser LT, Burroughs R, Golden MS, et al. Prevalence of total coronary occlusion during the early hours of transmural myocardial infarction. The New England journal of medicine. 1980; 303(16): 897-902.
2. Rentrop P, De Vivie ER, Karsch KR, Kreuzer H. Acute coronary occlusion with impending infarction as an angiographic complication relieved by a guide-wire recanalization. Clinical cardiology. 1978; 1(2): 101-6.
3. Danchin N, Juilliere Y, Cherrier F. [Intracoronary thrombolysis and coronary angioplasty in the acute stage of infarction]. La Revue de medecine interne / fondee par la Societe nationale francaise de medecine interne. 1988; 9(1): 49-53.
4. Granger CB, White HD, Bates ER, Ohman EM, Califf RM. A pooled analysis of coronary arterial patency and left ventricular function after intravenous thrombolysis for acute myocardial infarction. The American journal of cardiology. 1994; 74(12): 1220-8.
5. Van de Werf F. Thrombolysis for acute myocardial infarction. Haemostasis. 1994; 24(2): 65-8.
6. de Bono DP. What is the role of invasive intervention after coronary thrombolysis? European heart journal. 1991; 12 Suppl G: 43-6.
7. An international randomized trial comparing four thrombolytic strategies for acute myocardial infarction. The GUSTO investigators. The New England journal of medicine. 1993; 329(10): 673-82.
8. The effects of tissue plasminogen activator, streptokinase, or both on coronary-artery patency, ventricular function, and survival after acute myocardial infarction. The GUSTO Angiographic Investigators. The New England journal of medicine. 1993; 329(22): 1615-22.
9. Chesebro JH, Knatterud G, Roberts R, Borer J, Cohen LS, Dalen J, et al. Thrombolysis in Myocardial Infarction (TIMI) Trial, Phase I: A comparison between intravenous tissue plasminogen activator and intravenous streptokinase. Clinical findings through hospital discharge. Circulation. 1987; 76(1): 142-54.
10. Collen D, Lijnen HR. Tissue-type plasminogen activator: a historical perspective and personal account. Journal of thrombosis and haemostasis : JTH. 2004; 2(4): 541-6.
90
11. Llevadot J, Giugliano RP, Antman EM. Bolus fibrinolytic therapy in acute myocardial infarction. JAMA : the journal of the American Medical Association. 2001; 286(4): 442-9.
12. Intravenous NPA for the treatment of infarcting myocardium early; InTIME-II, a double-blind comparison of single-bolus lanoteplase vs accelerated alteplase for the treatment of patients with acute myocardial infarction. European heart journal. 2000; 21(24): 2005-13.
13. Smalling RW, Bode C, Kalbfleisch J, Sen S, Limbourg P, Forycki F, et al. More rapid, complete, and stable coronary thrombolysis with bolus administration of reteplase compared with alteplase infusion in acute myocardial infarction. RAPID Investigators. Circulation. 1995; 91(11): 2725- 32.
14. Bode C, Smalling RW, Berg G, Burnett C, Lorch G, Kalbfleisch JM, et al. Randomized comparison of coronary thrombolysis achieved with double- bolus reteplase (recombinant plasminogen activator) and front-loaded, accelerated alteplase (recombinant tissue plasminogen activator) in patients with acute myocardial infarction. The RAPID II Investigators. Circulation. 1996; 94(5): 891-8.
15. Smalling RW, Giesler G. The level I cardiovascular center: is it time? The American heart hospital journal. 2003; 1(2): 170-4.
16. Randomised, double-blind comparison of reteplase double-bolus administration with streptokinase in acute myocardial infarction (INJECT): trial to investigate equivalence. International Joint Efficacy Comparison of Thrombolytics. Lancet. 1995; 346(8971): 329-36.
17. A comparison of reteplase with alteplase for acute myocardial infarction. The Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO III) Investigators. The New England journal of medicine. 1997; 337(16): 1118-23.
18. Van De Werf F, Adgey J, Ardissino D, Armstrong PW, Aylward P, Barbash G, et al. Single-bolus tenecteplase compared with front-loaded alteplase in acute myocardial infarction: the ASSENT-2 double-blind randomised trial. Lancet. 1999; 354(9180): 716-22.
19. Efficacy and safety of tenecteplase in combination with enoxaparin, abciximab, or unfractionated heparin: the ASSENT-3 randomised trial in acute myocardial infarction. Lancet. 2001; 358(9282): 605-13.
20. Sinnaeve PR, Alexander JH, Bogaerts K, Belmans A, Wallentin L, Armstrong P, et al. Efficacy of tenecteplase in combination with enoxaparin,
91
abciximab, or unfractionated heparin: one-year follow-up results of the Assessment of the Safety of a New Thrombolytic-3 (ASSENT-3) randomized trial in acute myocardial infarction. American heart journal. 2004; 147(6): 993-8.
21. Topol EJ. Reperfusion therapy for acute myocardial infarction with fibrinolytic therapy or combination reduced fibrinolytic therapy and platelet glycoprotein IIb/IIIa inhibition: the GUSTO V randomised trial. Lancet. 2001; 357(9272): 1905-14.
22. Cannon CP, Gibson CM, McCabe CH, Adgey AA, Schweiger MJ, Sequeira RF, et al. TNK-tissue plasminogen activator compared with front- loaded alteplase in acute myocardial infarction: results of the TIMI 10B trial. Thrombolysis in Myocardial Infarction (TIMI) 10B Investigators. Circulation. 1998; 98(25): 2805-14.
23. Widimsky P, Groch L, Zelizko M, Aschermann M, Bednar F, Suryapranata H. Multicentre randomized trial comparing transport to primary angioplasty vs immediate thrombolysis vs combined strategy for patients with acute myocardial infarction presenting to a community hospital without a catheterization laboratory. The PRAGUE study. European heart journal. 2000; 21(10): 823-31.
24. Widimsky P, Budesinsky T, Vorac D, Groch L, Zelizko M, Aschermann M, et al. Long distance transport for primary angioplasty vs immediate thrombolysis in acute myocardial infarction. Final results of the randomized national multicentre trial--PRAGUE-2. European heart journal. 2003; 24(1): 94-104.
25. Andersen HR, Nielsen TT, Vesterlund T, Grande P, Abildgaard U, Thayssen P, et al. Danish multicenter randomized study on fibrinolytic therapy versus acute coronary angioplasty in acute myocardial infarction: rationale and design of the DANish trial in Acute Myocardial Infarction-2 (DANAMI-2). American heart journal. 2003; 146(2): 234-41.
26. Cannon CP, Gibson CM, Lambrew CT, Shoultz DA, Levy D, French WJ, et al. Relationship of symptom-onset-to-balloon time and door-to-balloon time with mortality in patients undergoing angioplasty for acute myocardial infarction. JAMA : the journal of the American Medical Association. 2000; 283(22): 2941-7.
27. Berger PB, Ellis SG, Holmes DR, Jr., Granger CB, Criger DA, Betriu A, et al. Relationship between delay in performing direct coronary angioplasty and early clinical outcome in patients with acute myocardial infarction: results from the global use of strategies to open occluded arteries in Acute Coronary Syndromes (GUSTO-IIb) trial. Circulation. 1999; 100(1): 14-20.
92
28. Juliard JM, Feldman LJ, Golmard JL, Himbert D, Benamer H, Haghighat T, et al. Relation of mortality of primary angioplasty during acute myocardial infarction to door-to-Thrombolysis In Myocardial Infarction (TIMI) time. The American journal of cardiology. 2003; 91(12): 1401-5.
29. De Luca G, Suryapranata H, Ottervanger JP, Antman EM. Time delay to treatment and mortality in primary angioplasty for acute myocardial infarction: every minute of delay counts. Circulation. 2004; 109(10): 1223-5.
30. Williams DO. Treatment delayed is treatment denied. Circulation. 2004; 109(15): 1806-8.
31. Keeley EC, Boura JA, Grines CL. Primary angioplasty versus intravenous thrombolytic therapy for acute myocardial infarction: a quantitative review of 23 randomised trials. Lancet. 2003; 361(9351): 13-20.
32. Cannon CP, Antman EM, Walls R, Braunwald E. Time as an Adjunctive Agent to Thrombolytic Therapy. Journal of thrombosis and thrombolysis. 1994; 1(1): 27-34.
33. Collen D. Thrombolytic therapy. Thrombosis and haemostasis. 1997; 78(1): 742-6.
34. Boersma E, Maas ACP, Deckers JW, Simoons ML. Early thrombolytic treatment in acute myocardial infarction: reappraisal of the golden hour. The Lancet. 1996; 348(9030): 771-5.
35. Huber K, Maurer G. Thrombolytic therapy in acute myocardial infarction. Seminars in thrombosis and hemostasis. 1996; 22(1): 15-26.
36. van 't Hof AW, Rasoul S, van de Wetering H, Ernst N, Suryapranata H, Hoorntje JC, et al. Feasibility and benefit of prehospital diagnosis, triage, and therapy by paramedics only in patients who are candidates for primary angioplasty for acute myocardial infarction. American heart journal. 2006; 151(6): 1255 e1-5.
37. Postma S, Dambrink JH, de Boer MJ, Gosselink AT, Eggink GJ, van de Wetering H, et al. Prehospital triage in the ambulance reduces infarct size and improves clinical outcome. American heart journal. 2011; 161(2): 276-82.
38. Zeymer U, Arntz HR, Dirks B, Ellinger K, Genzwurker H, Nibbe L, et al. Reperfusion rate and inhospital mortality of patients with ST segment elevation myocardial infarction diagnosed already in the prehospital phase: results of the German Prehospital Myocardial Infarction Registry (PREMIR). Resuscitation. 2009; 80(4): 402-6.
93
39. MacCallum AG, Stafford PJ, Jones C, Vincent R, Perez-Avila C, Chamberlain DA. Reduction in hospital time to thrombolytic therapy by audit of policy guidelines. European heart journal. 1990; 11 Suppl F: 48-52.
40. Gibson CM, Pride YB, Frederick PD, Pollack CV, Jr., Canto JG, Tiefenbrunn AJ, et al. Trends in reperfusion strategies, door-to-needle and door-to-balloon times, and in-hospital mortality among patients with ST- segment elevation myocardial infarction enrolled in the National Registry of Myocardial Infarction from 1990 to 2006. American heart journal. 2008; 156(6): 1035-44.
41. Ting HH, Bradley EH, Wang Y, Nallamothu BK, Gersh BJ, Roger VL, et al. Delay in presentation and reperfusion therapy in ST-elevation myocardial infarction. The American journal of medicine. 2008; 121(4): 316- 23.
42. Kushner FG, Hand M, Smith SC, Jr., King SB, 3rd, Anderson JL, Antman EM, et al. 2009 focused updates: ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction (updating the 2004 guideline and 2007 focused update) and ACC/AHA/SCAI guidelines on percutaneous coronary intervention (updating the 2005 guideline and 2007 focused update): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Catheterization and cardiovascular interventions : official journal of the Society for Cardiac Angiography & Interventions. 2009; 74(7): E25-68.
43. Eagle KA, Nallamothu BK, Mehta RH, Granger CB, Steg PG, Van de Werf F, et al. Trends in acute reperfusion therapy for ST-segment elevation myocardial infarction from 1999 to 2006: we are getting better but we have got a long way to go. European heart journal. 2008; 29(5): 609-17.
44. Nallamothu BK, Bates ER, Herrin J, Wang Y, Bradley EH, Krumholz HM. Times to treatment in transfer patients undergoing primary percutaneous coronary intervention in the United States: National Registry of Myocardial Infarction (NRMI)-3/4 analysis. Circulation. 2005; 111(6): 761-7.
45. Pinto DS, Kirtane AJ, Nallamothu BK, Murphy SA, Cohen DJ, Laham RJ, et al. Hospital delays in reperfusion for ST-elevation myocardial infarction: implications when selecting a reperfusion strategy. Circulation. 2006; 114(19): 2019-25.
46. Canto JG, Rogers WJ, Bowlby LJ, French WJ, Pearce DJ, Weaver WD. The prehospital electrocardiogram in acute myocardial infarction: is its full potential being realized? National Registry of Myocardial Infarction 2 Investigators. Journal of the American College of Cardiology. 1997; 29(3): 498-505.
94
47. Karagounis L, Ipsen SK, Jessop MR, Gilmore KM, Valenti DA, Clawson JJ, et al. Impact of field-transmitted electrocardiography on time to in-hospital thrombolytic therapy in acute myocardial infarction. The American journal of cardiology. 1990; 66(10): 786-91.
48. Kudenchuk PJ, Ho MT, Weaver WD, Litwin PE, Martin JS, Eisenberg MS, et al. Accuracy of computer-interpreted electrocardiography in selecting patients for thrombolytic therapy. MITI Project Investigators. Journal of the American College of Cardiology. 1991; 17(7): 1486-91.
49. O'Rourke MF, Cook A, Carroll G, Gallagher D, Hall J. Accuracy of a portable interpretive ECG machine in diagnosis of acute evolving myocardial infarction. Australian and New Zealand journal of medicine. 1992; 22(1): 9- 13.
50. Weaver WD, Eisenberg MS, Martin JS, Litwin PE, Shaeffer SM, Ho MT, et al. Myocardial Infarction Triage and Intervention Project--phase I: patient characteristics and feasibility of prehospital initiation of thrombolytic therapy. Journal of the American College of Cardiology. 1990; 15(5): 925-31.
51. Welsh RC, Ornato J, Armstrong PW. Prehospital management of acute ST-elevation myocardial infarction: a time for reappraisal in North America. American heart journal. 2003; 145(1): 1-8.
52. Mathew TP, Menown IB, McCarty D, Gracey H, Hill L, Adgey AA. Impact of pre-hospital care in patients with acute myocardial infarction compared with those first managed in-hospital. European heart journal. 2003; 24(2): 161-71.
53. Adgey AA, Zaidi SA. Mobile coronary care teams. British medical journal. 1969; 4(5680): 427-8.
54. Morrow DA, Antman EM, Sayah A, Schuhwerk KC, Giugliano RP, deLemos JA, et al. Evaluation of the time saved by prehospital initiation of reteplase for ST-elevation myocardial infarction: results of The Early Retavase-Thrombolysis in Myocardial Infarction (ER-TIMI) 19 trial. Journal of the American College of Cardiology. 2002; 40(1): 71-7.
55. Wallentin L, Goldstein P, Armstrong PW, Granger CB, Adgey AA, Arntz HR, et al. Efficacy and safety of tenecteplase in combination with the low-molecular-weight heparin enoxaparin or unfractionated heparin in the prehospital setting: the Assessment of the Safety and Efficacy of a New Thrombolytic Regimen (ASSENT)-3 PLUS randomized trial in acute myocardial infarction. Circulation. 2003; 108(2): 135-42.
95
56. Danchin N, Blanchard D, Steg PG, Sauval P, Hanania G, Goldstein P, et al. Impact of prehospital thrombolysis for acute myocardial infarction on 1- year outcome: results from the French Nationwide USIC 2000 Registry. Circulation. 2004; 110(14): 1909-15.
57. Bonnefoy E, Lapostolle F, Leizorovicz A, Steg G, McFadden EP, Dubien PY, et al. Primary angioplasty versus prehospital fibrinolysis in acute myocardial infarction: a randomised study. Lancet. 2002; 360(9336): 825-9.
58. Steg PG, Bonnefoy E, Chabaud S, Lapostolle F, Dubien PY, Cristofini P, et al. Impact of time to treatment on mortality after prehospital fibrinolysis or primary angioplasty: data from the CAPTIM randomized clinical trial. Circulation. 2003; 108(23): 2851-6.
59. Bonnefoy E, Steg PG, Boutitie F, Dubien PY, Lapostolle F, Roncalli J, et al. Comparison of primary angioplasty and pre-hospital fibrinolysis in acute myocardial infarction (CAPTIM) trial: a 5-year follow-up. European heart journal. 2009; 30(13): 1598-606.
60. Morrison LJ, Verbeek PR, McDonald AC, Sawadsky BV, Cook DJ. Mortality and prehospital thrombolysis for acute myocardial infarction: A meta-analysis. JAMA : the journal of the American Medical Association. 2000; 283(20): 2686-92.
61. Vaisanen O, Makijarvi M, Lund V, Silfvast T. Arrhrythmias and haemodynamic effects associated with early versus late prehospital thrombolysis for acute myocardial infarction. Resuscitation. 2004; 62(2): 175- 80.
62. Arntz HR, Wenzel V, Dissmann R, Marschalk A, Breckwoldt J, Muller D. Out-of-hospital thrombolysis during cardiopulmonary resuscitation in patients with high likelihood of ST-elevation myocardial infarction. Resuscitation. 2008; 76(2): 180-4.
63. Keeling P, Hughes D, Price L, Shaw S, Barton A. Safety and feasibility of prehospital thrombolysis carried out by paramedics. BMJ (Clinical research ed). 2003; 327(7405): 27-8.
64. Pedley DK, Bissett K, Connolly EM, Goodman CG, Golding I, Pringle TH, et al. Prospective observational cohort study of time saved by prehospital thrombolysis for ST elevation myocardial infarction delivered by paramedics. BMJ (Clinical research ed). 2003; 327(7405): 22-6.
65. Welsh RC, Travers A, Senaratne M, Williams R, Armstrong PW. Feasibility and applicability of paramedic-based prehospital fibrinolysis in a large North American center. American heart journal. 2006; 152(6): 1007-14.
96
66. Jaffe R, Halon DA, Karkabi B, Goldstein J, Rubinshtein R, Flugelman MY, et al. Thrombolysis followed by early revascularization: an effective reperfusion strategy in real world patients with ST-elevation myocardial infarction. Cardiology. 2007; 107(4): 329-36.
67. Stone GW, Grines CL, Cox DA, Garcia E, Tcheng JE, Griffin JJ, et al. Comparison of angioplasty with stenting, with or without abciximab, in acute myocardial infarction. The New England journal of medicine. 2002; 346(13): 957-66.
68. Ross AM, Coyne KS, Reiner JS, Greenhouse SW, Fink C, Frey A, et al. A randomized trial comparing primary angioplasty with a strategy of short- acting thrombolysis and immediate planned rescue angioplasty in acute myocardial infarction: the PACT trial. PACT investigators. Plasminogen- activator Angioplasty Compatibility Trial. Journal of the American College of Cardiology. 1999; 34(7): 1954-62.
69. Scheller B, Hennen B, Hammer B, Walle J, Hofer C, Hilpert V, et al. Beneficial effects of immediate stenting after thrombolysis in acute myocardial infarction. Journal of the American College of Cardiology. 2003; 42(4): 634-41.
70. Fernandez-Aviles F, Alonso JJ, Castro-Beiras A, Vazquez N, Blanco J, Alonso-Briales J, et al. Routine invasive strategy within 24 hours of thrombolysis versus ischaemia-guided conservative approach for acute myocardial infarction with ST-segment elevation (GRACIA-1): a randomised controlled trial. Lancet. 2004; 364(9439): 1045-53.
71. Keeley EC, Boura JA, Grines CL. Comparison of primary and facilitated percutaneous coronary interventions for ST-elevation myocardial infarction: quantitative review of randomised trials. Lancet. 2006; 367(9510): 579-88.
72. Primary versus tenecteplase-facilitated percutaneous coronary intervention in patients with ST-segment elevation acute myocardial infarction (ASSENT-4 PCI): randomised trial. Lancet. 2006; 367(9510): 569-78.
73. Ellis SG, Tendera M, de Belder MA, van Boven AJ, Widimsky P, Janssens L, et al. Facilitated PCI in patients with ST-elevation myocardial infarction. The New England journal of medicine. 2008; 358(21): 2205-17.
74. Denktas AE, Athar H, Henry TD, Larson DM, Simons M, Chan RS, et al. Reduced-dose fibrinolytic acceleration of ST-segment elevation myocardial infarction treatment coupled with urgent percutaneous coronary intervention compared to primary percutaneous coronary intervention alone results of the
97
AMICO (Alliance for Myocardial Infarction Care Optimization) Registry. JACC Cardiovascular interventions. 2008; 1(5): 504-10.
75. Le May MR, Wells GA, Labinaz M, Davies RF, Turek M, Leddy D, et al. Combined angioplasty and pharmacological intervention versus thrombolysis alone in acute myocardial infarction (CAPITAL AMI study). Journal of the American College of Cardiology. 2005; 46(3): 417-24.
76. Di Mario C, Dudek D, Piscione F, Mielecki W, Savonitto S, Murena E, et al. Immediate angioplasty versus standard therapy with rescue angioplasty after thrombolysis in the Combined Abciximab REteplase Stent Study in Acute Myocardial Infarction (CARESS-in-AMI): an open, prospective, randomised, multicentre trial. Lancet. 2008; 371(9612): 559-68.
77. Cantor WJ, Fitchett D, Borgundvaag B, Ducas J, Heffernan M, Cohen EA, et al. Routine early angioplasty after fibrinolysis for acute myocardial infarction. The New England journal of medicine. 2009; 360(26): 2705-18.
78. Armstrong PW. A comparison of pharmacologic therapy with/without timely coronary intervention vs. primary percutaneous intervention early after ST-elevation myocardial infarction: the WEST (Which Early ST-elevation myocardial infarction Therapy) study. European heart journal. 2006; 27(13): 1530-8.
79. Silber S. [Evidence-based management of ST-segment elevation myocardial infarction (STEMI). Latest guidelines of the European Society of Cardiology (ESC) 2010]. Herz. 2010; 35(8): 558-64.
80. L’infarto miocardico acuto in Toscana, 1995-2008: trend temporali e differenze territoriali di incidenza. 2011 18.08.2011 [cited 20.04.2012]; Available from: http://www.ars.toscana.it/infarto
81. ASF, Osservatorio_di_Epidemiologia. Registro regionale toscano dell'infarto miocardico acuto - Primo rapporto. 2005 19.01.2012 [cited
04.04.2012]; Available from:
http://www.ars.toscana.it/web/guest/pub11864?p_p_id=62_INSTANCE_42oB &p_p_lifecycle=0&p_p_state=maximized&p_p_mode=view&_62_INSTANC E_42oB_struts_action=/journal_articles/view&_62_INSTANCE_42oB_group Id=11864&_62_INSTANCE_42oB_articleId=22048