Specyficznym zagadaniem dotyczącym czasu trwania terapii przeciwpłytkowej jest postępowanie w przypadku konieczności jego zaprzestania przed zabiegiem chirurgicznym w obrębie układu krążenia. Jak wspomniano wcześniej, zgodnie z zarejestrowaną charakterystyką produktów leczniczych odstawienie klopidogrelu powinno nastąpić 5, tikagreloru 5-7, a prasugrelu 7 dni przed operacją. Takie postępowanie jest ponadto zgodne z aktualnymi wytycznymi towarzystw kardiologicznych (5 dni dla klopidogrelu, 3-5 dni dla tikagreloru i 7 dni dla prasugrelu) [2,5]. Przedwczesne przerwanie terapii przeciwpłytkowej nie powinno być natomiast zalecane w przypadku planowych zabiegów chirurgii pozasercowej, szczególnie obarczonych stosunkowo małym ryzykiem powikłań krwotocznych.

Podsumowanie

Obecnie w Polsce nadal dominującym modelem leczenia przeciwpłytkowego jest kwas acetylosalicylowy, klopidogrel i niefrakcjonowana heparyna u chorych leczonych z powodu OZW oraz 12-miesięczna podwójna terapia przeciwpłytkowa tymi lekami [43]. Penetracja nowych leków przeciwpłytkowych jest zadziwiająco niska, co może być trudno akceptowalne w świetle dostępnych danych naukowych i aktualnych wytycznych europejskich. Nowe leki przeciwpłytkowe – prasugrel i tikagrelor – wydają się równoważne. Decyzja o wyborze konkretnego preparatu powinna być podjęta głównie na podstawie jego dostępności i oceny przeciwwskazań do ich użycia. Powinny być one stosowane w coraz szerszej populacji pacjentów z OZW, po wykluczeniu podwyższonego ryzyka krwawień, zwłaszcza przebytego incydentu mózgowego. Należy zalecać terapię ASA i prasugrelem lub tikagrelorem przez 12 miesięcy od OZW. Czas jej trwania może być skrócony w przypadku zwiększonego ryzyka krwawień, ale nie powinien być krótszy niż czas terapii warunkowany rodzajem implantowanego stentu. Obecnie prowadzone są badania dotyczące nowych schematów leczenia przeciwpłytkowego (podwójna terapia przeciwpłytkowa vs pojedyncza z zastosowaniem wyłącznie leku nowej generacji) lub alternatywnych połączeń leków (inhibitor P2Y12 i inhibitor receptora trombinowego). Miejmy nadzieję, że ich wyniki wpłyną na dalszą poprawę profilu skuteczności i bezpieczeństwa stosowanego leczenia przeciwpłytkowego oraz doprowadzą do dalszej redukcji śmiertelności w chorobach układu krążenia.

Piśmiennictwo

1. Wijns W, Kolh P, Danchin N, et al. Guidelines on myocardial revascularization: The Task Force on Myocardial Revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J 2010; 31: 2501-2555.

2. Hamm CW, Bassand JP, Agewall S, et al. ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: The Task Force for the management of acute coronary syndromes (ACS) in patients presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J 2011; 32: 2999-3054.

3. Steg PG, James SK, Atar D, et al. ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: The Task Force on the management of ST-segment elevation acute myocardial infarction of the European Society of Cardiology (ESC). Eur Heart J 2012; [ogłoszone on-line przed
publikacją].

4. Kushner FG, Hand M, Smith SC Jr, 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. Circulation 2009; 120: 2271-2306.

5. Jneid H, Anderson JL, Wright RS, et al. 2012 ACCF/AHA Focused Update of the Guideline for the Management of Patients With Unstable Angina/Non-ST-Elevation Myocardial Infarction (Updating the 2007 Guideline and Replacing the 2011 Focused Update): A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation 2012; 126: 875-910.

6. Dziewierz A, Dudek D, Heba G, et al. Inter-individual variability in response to clopidogrel in patients with coronary artery disease. Kardiol Pol 2005; 62: 108-117.

7. Farid NA, Payne CD, Small DS, et al. Cytochrome P450 3A inhibition by ketoconazole affects prasugrel and clopidogrel pharmacokinetics and pharmacodynamics differently. Clin Pharmacol Ther 2007; 81: 735-741.

8. Jakubowski JA, Matsushima N, Asai F, et al. A multiple dose study of prasugrel (CS-747), a novel thienopyridine P2Y12 inhibitor, compared with clopidogrel in healthy humans. Br J Clin Pharmacol 2007; 63: 421-430.

9. Wiviott SD, Trenk D, Frelinger AL, et al. Prasugrel compared with high loading- and maintenance-dose clopidogrel in patients with planned percutaneous coronary intervention: the Prasugrel in Comparison to Clopidogrel for Inhibition of Platelet Activation and Aggregation-Thrombolysis in Myocardial Infarction 44 trial. Circulation 2007; 116: 2923-2932.

10. Jernberg T, Payne CD, Winters KJ, et al. Prasugrel achieves greater inhibition of platelet aggregation and a lower rate of non-responders compared with clopidogrel in aspirin-treated patients with stable coronary artery disease. Eur Heart J 2006; 27: 1166-1173.

11. Heestermans AA, van Werkum JW, Taubert D, et al. Impaired bioavailability of clopidogrel in patients with a ST-segment elevation myocardial infarction. Thromb Res 2008; 122: 776-781.

12. Wiviott SD, Antman EM, Winters KJ, et al. Randomized comparison of prasugrel (CS-747, LY640315), a novel thienopyridine P2Y12 antagonist, with clopidogrel in percutaneous coronary intervention: results of the Joint Utilization of Medications to Block Platelets Optimally (JUMBO)-TIMI 26 trial. Circulation 2005; 111: 3366-3373.

13. Wiviott SD, Braunwald E, McCabe CH, et al. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2007; 357: 2001-2015.

14. Antman EM, Wiviott SD, Murphy SA, et al. Early and late benefits of prasugrel in patients with acute coronary syndromes undergoing percutaneous coronary intervention: a TRITON-TIMI 38 (TRial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet InhibitioN with Prasugrel-Thrombolysis In Myocardial Infarction) analysis. J Am Coll Cardiol 2008; 51: 2028-2033.

15. Wiviott SD, Braunwald E, McCabe CH, et al. Intensive oral antiplatelet therapy for reduction of ischaemic events including stent thrombosis in patients with acute coronary syndromes treated with percutaneous coronary intervention and stenting in the TRITON-TIMI 38 trial: a subanalysis of a randomised trial. Lancet 2008; 371: 1353-1363.

16. Montalescot G, Wiviott SD, Braunwald E, et al. Prasugrel compared with clopidogrel in patients undergoing percutaneous coronary intervention for ST-elevation myocardial infarction (TRITON-TIMI 38): double-blind, randomised controlled trial. Lancet 2009; 373: 723-731.

17. Wiviott SD, Braunwald E, Angiolillo DJ, et al. Greater clinical benefit of more intensive oral antiplatelet therapy with prasugrel in patients with diabetes mellitus in the trial to assess improvement in therapeutic outcomes by optimizing platelet inhibition with prasugrel-Thrombolysis in Myocardial Infarction 38. Circulation 2008; 118: 626-1636.

18. Montalescot G, Sideris G, Cohen R, et al. Prasugrel compared with high-dose clopidogrel in acute coronary syndrome. The randomised, double-blind ACAPULCO study. Thromb Haemost 2010; 103: 213-223.

19. Husted S, Emanuelsson H, Heptinstall S, et al. Pharmacodynamics, pharmacokinetics, and safety of the oral reversible P2Y12 antagonist AZD6140 with aspirin in patients with atherosclerosis: a double-blind comparison to clopidogrel with aspirin. Eur Heart J 2006; 27: 1038-1047.

20. Gurbel PA, Bliden KP, Butler K, et al. Response to ticagrelor in clopidogrel nonresponders and responders and effect of switching therapies: the RESPOND study. Circulation 2010; 121: 1188-1199.

21. Wallentin L, Becker RC, Budaj A, et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2009; 361: 1045-1057.

22. Cannon CP, Harrington RA, James S, et al. Comparison of ticagrelor with clopidogrel in patients with a planned invasive strategy for acute coronary syndromes (PLATO): a randomised double-blind study. Lancet 2010; 375: 283-293.

23. James S, Budaj A, Aylward P, et al. Ticagrelor versus clopidogrel in acute coronary syndromes in relation to renal function: results from the Platelet Inhibition and Patient Outcomes (PLATO) trial. Circulation 2010; 122: 1056-1067.

24. James S, Angiolillo DJ, Cornel JH, et al. Ticagrelor vs. clopidogrel in patients with acute coronary syndromes and diabetes: a substudy from the PLATelet inhibition and patient Outcomes (PLATO) trial. Eur Heart J 2010.

25. Held C, Asenblad N, Bassand JP, et al. Ticagrelor Versus Clopidogrel in Patients With Acute Coronary Syndromes Undergoing Coronary Artery Bypass Surgery Results From the PLATO (Platelet Inhibition and Patient Outcomes) Trial. J Am Coll Cardiol 2010.

26. Storey RF, Wilcox RG, Heptinstall S. Comparison of the pharmacodynamic effects of the platelet ADP receptor antagonists clopidogrel and AR-C69931MX in patients with ischaemic heart disease. Platelets 2002; 13: 407-413.

27. Bhatt DL, Lincoff AM, Gibson CM, et al. Intravenous platelet blockade with cangrelor during PCI. N Engl J Med 2009; 361: 2330-2341.

28. Harrington RA, Stone GW, McNulty S, et al. Platelet inhibition with cangrelor in patients undergoing PCI. N Engl J Med 2009; 361: 2318-2329.

29. Steinhubl SR, Oh JJ, Oestreich JH, et al. Transitioning patients from cangrelor to clopidogrel: pharmacodynamic evidence of a competitive effect. Thromb Res 2008; 121: 527-534.

30. White HD, Chew DP, Dauerman HL, et al. Reduced immediate ischemic events with cangrelor in PCI: a pooled analysis of the CHAMPION trials using the universal definition of myocardial infarction. Am Heart J 2012; 163: 182-190.

31. Leonardi S, Mahaffey KW, White HD, et al. Rationale and design of the Cangrelor versus standard therapy to acHieve optimal Management of Platelet InhibitiON PHOENIX trial. Am Heart J 2012; 163: 768-776.

32. Angiolillo DJ, Schneider DJ, Bhatt DL, et al. Pharmacodynamic effects of cangrelor and clopidogrel: the platelet function substudy from the cangrelor versus standard therapy to achieve optimal management of platelet inhibition (CHAMPION) trials. J Thromb Thrombolysis 2012; 34: 44-55.

33. Berger JS, Roe MT, Gibson CM, et al. Safety and feasibility of adjunctive antiplatelet therapy with intravenous elinogrel, a direct-acting and reversible P2Y12 ADP-receptor antagonist, before primary percutaneous intervention in patients with ST-elevation myocardial infarction: the Early Rapid ReversAl of platelet thromboSis with intravenous Elinogrel before PCI to optimize reperfusion in acute Myocardial Infarction (ERASE MI) pilot trial. Am Heart J 2009; 158:998-1004.

34. Welsh RC, Rao SV, Zeymer U, et al. A randomized, double-blind, active-controlled phase 2 trial to evaluate a novel selective and reversible intravenous and oral P2Y12 inhibitor elinogrel versus clopidogrel in patients undergoing nonurgent percutaneous coronary intervention: the INNOVATE-PCI trial. Circ Cardiovasc Interv 2012; 5: 336-346.

35. Becker RC, Moliterno DJ, Jennings LK, et al. Safety and tolerability of SCH 530348 in patients undergoing non-urgent percutaneous coronary intervention: a randomised, double-blind, placebo-controlled phase II study. Lancet 2009; 373: 919-928.

36. Goto S, Yamaguchi T, Ikeda Y, et al. Safety and exploratory efficacy of the novel thrombin receptor (PAR-1) antagonist SCH530348 for non-ST-segment elevation acute coronary syndrome. J Atheroscler Thromb 2010; 17: 156-164.

37. Tricoci P, Roe MT, Mulgund J, et al. Clopidogrel to treat patients with non-ST-segment elevation acute coronary syndromes after hospital discharge. Arch Intern Med 2006; 166: 806-811.

38. Morrow DA, Braunwald E, Bonaca MP, et al. Vorapaxar in the secondary prevention of atherothrombotic events. N Engl J Med 2012; 366: 1404-1413.

39. Goto S, Ogawa H, Takeuchi M, et al. Double-blind, placebo-controlled Phase II studies of the protease-activated receptor 1 antagonist E5555 (atopaxar) in Japanese patients with acute coronary syndrome or high-risk coronary artery disease. Eur Heart J 2010.

40. O'Donoghue ML, Bhatt DL, Wiviott SD, et al. Safety and tolerability of atopaxar in the treatment of patients with acute coronary syndromes: the lessons from antagonizing the cellular effects of Thrombin-Acute Coronary Syndromes Trial. Circulation 2011; 123: 1843-1853.

41. Wiviott SD, Flather MD, O'Donoghue ML, et al. Randomized trial of atopaxar in the treatment of patients with coronary artery disease: the lessons from antagonizing the cellular effect of Thrombin-Coronary Artery Disease Trial. Circulation 2011; 123: 1854-1863.

42. Chatterjee S, Sharma A, Mukherjee D. PAR-1 antagonists: current state of evidence. J Thromb Thrombolysis 2012.

43. Dudek D, Filipiak KJ, Stepinska J, et al. New model of the optimal oral antiplatelet treatment in patients with the ST-segment elevation myocardial infarction in Poland. Polish Cardiac Society statement. Kardiol Pol 2011; 69: 986-994.

44. Dudek D, Filipiak KJ, Stepinska J, et al. New model of the optimal oral antiplatelet treatment in patients with the
ST-segment elevation myocardial infarction in Poland – authors' reply. Kardiol Pol 2012; 70: 317-320.

45. Montalescot G, Bolognese L, Dudek D, et al. A comparison of prasugrel at the time of percutaneous coronary intervention or as pretreatment at the time of diagnosis in patients with non-ST-segment elevation myocardial infarction: design and rationale for the ACCOAST study. Am Heart J 2011; 161: 650-656.

46. Biondi-Zoccai G, Lotrionte M, Agostoni P, et al. Adjusted indirect comparison meta-analysis of prasugrel versus ticagrelor for patients with acute coronary syndromes. Int J Cardiol 2010.

47. Bhatt DL, Flather MD, Hacke W, et al. Patients with prior myocardial infarction, stroke, or symptomatic peripheral arterial disease in the CHARISMA trial. J Am Coll Cardiol 2007; 49: 1982-1988.

48. Gwon HC, Hahn JY, Park KW, et al. Six-month versus 12-month dual antiplatelet therapy after implantation of drug-eluting stents: the Efficacy of Xience/Promus Versus Cypher to Reduce Late Loss After Stenting (EXCELLENT) randomized, multicenter study. Circulation 2012; 125: 505-513.

49. Valgimigli M, Campo G, Monti M, et al. Short- versus long-term duration of dual-antiplatelet therapy after coronary stenting: a randomized multicenter trial. Circulation 2012; 125: 2015-2026.

50. Sangiorgi GM, Morice MC, Bramucci E, et al. Evaluating the safety of very short-term (10 days) dual antiplatelet therapy after Genous bio-engineered R stent implantation: the multicentre pilot GENOUS trial. EuroIntervention 2011; 7: 813-819.

Do góry