Badanie OPTIMIZE – czy można skrócić okres podwójnej terapii przeciwpłytkowej po implantacji stentu ?

Marzec 3, 2014  |  Udostępnij  | 

Obecne wytyczne Europejskiego Towarzystwa Kardiologicznego (ESC) zalecają stosowanie podwójnej terapii przeciwkrzepliwej przez okres 12 miesięcy od przezskórnej interwencji wieńcowej (PCI). Przyjmowanie kwasu acetylosalicylowego (ASA) w połączniu z klopidogrelem ma zapobiegać zakrzepicy, do jakiej może dochodzić ze względu na kontakt krwi z ciałem obcym, jakim jest implantowany stent. Jest to szczególnie ważne w przypadku stentów typu DES, powlekanych lekami antymitotycznymi. Substancje te mają zapobiegać restenozie, ale jednocześnie opóźniają powleczenie metalowych części śródbłonkiem naczyniowym, co wydłuża czas, w którym czynniki krzepnięcia mają bezpośrednią styczność z ciałem obcym. Wspomniane zalecenie ESC zostało uogólnione na wszystkie rodzaje stentów, podczas gdy nie ma badań, które wskazywałyby optymalny czas podwójnej terapii przeciwpłytkowej dla poszczególnych leków antymitotycznych.

Grupa naukowców z Brazylii, w ramach badania nazwanego w skrócie OPTIMIZE [1], zbadała, czy stenty DES uwalniające zotarolimus rzeczywiście wymagają pełnego, 12 miesięcznego okresu jednoczesnego podawania ASA i klopidogrelu. Jako rozwiązanie alternatywne przyjęto skrócenie czasu przyjmowania obu leków do 3 miesięcy i po uzyskaniu zgody stosownych komisji etycznych przystąpiono do realizacji projektu. Badanie OPTIMIZE przeprowadzono w 33 ośrodkach położonych na terenie Brazylii pomiędzy kwietniem 2010 roku a marcem 2012. W tym okresie do eksperymentu włączono 3119 pacjentów ze stabilną chorobą niedokrwienną lub z ostrym zespołem wieńcowym niskiego ryzyka w wywiadzie, po przebytym PCI z wszczepieniem stentu DES uwalniającego zotarolimus. Po skutecznej implantacji chorzy byli wypisywani z losowo przydzielonymi zaleceniami dalszej terapii farmakologicznej. Pacjenci randomizowani do grupy badanej (n=1563) przyjmowali codziennie ASA (dawka 100-200 mg) oraz klopidogrel (75 mg/dobę) przez 3 miesiące. Osoby, które trafiły do grupy kontrolnej (n=1556) analogiczny schemat leczenia stosowały przez 12 miesięcy. Oczywiście przyjmowanie preparatów przeciwpłytkowych było przerywane wcześniej, jeśli wystąpiły przeciwwskazania do ich stosowania. Wizyty kontrolne zaplanowano po 1, 3, 6 i 12 miesiącach od momentu włączenia do badania. Na pierwszorzędowy, złożony punkt końcowy składały się: śmierć z dowolnej przyczyny, zawał serca, udar mózgu oraz poważne krwawienia. Wymienione zdarzenia wystąpiły łącznie u 93 pacjentów  z grupy przyjmującej podwójną terapię przeciwpłytkową przez 3 miesiące oraz u 90 chorych leczonych przez rok. Średnia częstość, z jaką występował pierwszorzędowy punkt końcowy, wynosiła odpowiednio: 128 zdarzeń/rok (8,3%) w grupie badanej i 114 zdarzeń/rok (7,4%) w grupie kontrolnej. Uzyskane dysproporcje nie były istotne statystycznie. Co więcej, nie zaobserwowano różnic także, gdy analizie poddano wyłącznie okres pomiędzy 90 a 360 dniem od rozpoczęcia obserwacji, czyli czas, w którym część pacjentów ciągle przyjmowała ASA i klopidogrel, a część pozostawała bez leków blokujących agregację płytek. Nie odnotowano także zwiększenia częstości przypadków zakrzepicy w implantowanym stencie po odstawieniu preparatów antyagregacyjnych.

Wnioski płynące z omawianego badania mogą być zastosowane jedynie do pacjentów, którym implantowano stent uwalniający zotarolimus, a którzy wyjściowo prezentowali objawy stabilnej choroby niedokrwiennej serca lub przebyli ostry zespołów wieńcowy niskiego ryzyka. Niemniej jednak uzyskane wyniki pokazują, że istnieją grupy chorych, u których stosowanie terapii dwoma lekami przeciwpłytkowymi można bezpiecznie ograniczyć do pierwszych 3 miesięcy po PCI.

1. F. Feres et al., Three vs Twelve Months of Dual Antiplatelet Therapy After Zotarolimus-Eluting Stents – The OPTIMIZE Randomized Trial. JAMA. 31 Oct 2013 [Epub ahead of print]



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