Kongres ESC Amsterdam 2013 – nowe doustne antykoagulanty – oczekiwania a rzeczywistość

Październik 14, 2013  |  Udostępnij  | 

Zgodnie z zapowiedzią z poprzedniego artykułu, w poniższym tekście zajmiemy się kolejnymi badaniami, których wyniki upubliczniono podczas odbywającej się niedawno w Amsterdamie konferencji Europejskiego Towarzystwa Kardiologicznego (ESC). Wspólnym mianownikiem będzie ich temat – nowe doustne antykoagulanty i ich rola w zapobieganiu powikłaniom zakrzepowo-zatorowym.

Pierwsze z badań[1], określone akronimem RE-ALIGN, miało na celu ocenę skuteczności dabigatranu w zapobieganiu zatorowości u pacjentów z wszczepioną sztuczną zastawką serca. Jak wiadomo, ten bezpośredni inhibitor trombiny okazał się lepszy od tradycyjnych antykoagulantów w grupie pacjentów z niezastawkowym migotaniem przedsionków, toteż nadzieje związane z opisywanym eksperymentem były stosunkowo wysokie. Protokół badania zakładał włączenie chorych poddanych wszczepieniu mechanicznej zastawki mitralnej, aortalnej, bądź obu jednocześnie, a następnie podzielenie ich na dwie grupy – badaną – leczoną dabigatranem oraz kontrolną – przyjmującą warfarynę. Niestety eksperymentu nie udało się przeprowadzić według pierwotnego projektu, gdyż po włączeniu 252 pacjentów musiał on zostać przerwany z powodu zagrożenia dla osób badanych. Ryzyko, zarówno krwawienia, jak i powikłań zakrzepowo-zatorowych było wyraźnie większe w grupie przyjmujących dabigatran. Złożony punkt końcowy, na który składały się udar mózgu, przejściowe epizody niedokrwienne (TIA), zawał serca oraz zgon, wystąpił u 9% (15 chorych) w grupie badanej, oraz u 5% (4 chorych) w grupie kontrolnej. Poważne krwawienia stały się udziałem 4% osób przyjmujących dabigatran oraz 2% spośród leczonych warfaryną. Według ekspertów, komentujących publikację w trakcie konferencji, uzyskane wyniki mogą być efektem innego mechanizmu działania obu porównywanych leków. Dabigatran, będący bezpośrednim inhibitorem trombiny, nie zapobiega aktywacji kaskady krzepnięcia w kontakcie z ciałem obcym. Warfaryna, antagonista witaminy K, lepiej radzi sobie z tym problemem.

Inne ciekawe badanie[2], którego wyniki zaprezentowano w Amsterdamie, dotyczyło zastosowania otamiksabanu u pacjentów z ostrym zespołem wieńcowym bez uniesienia odcinka ST (NST-ACS) poddawanych zabiegom kardiologii inwazyjnej. TAO, jak zostało nazwane to badanie, zakładało porównanie nowego, wciąż jeszcze testowanego antykoagulantu z klasycznym leczeniem heparyną niefrakcjonowaną i eptifibatydem. W eksperymencie wzięło udział 13 tysięcy chorych z NST-ACS pośredniego i dużego ryzyka, z których połowa została losowo przydzielona do grupy badanej – leczonej otamiksabanem według schematu 0,08mg/kg masy ciała w bolusie, a następnie wlew ciągły z prędkością 0,1 mg/kg/h. Chorych obserwowano przez 7 kolejnych dni. Do zdarzeń składających się na pierwszorzędowy złożony punkt końcowy zaliczono zgon z jakiejkolwiek przyczyny oraz zawał serca. Porównując obie grupy nie odnotowano istotnej statystycznie różnicy w jego występowaniu. Pierwszorzędowy punkt końcowy wystąpił odpowiednio u 5,7% pacjentów leczonych heparyną niefrakcjonowaną i eptifibatydem oraz u 5,5% chorych, którym podawano otamiksaban. Jednocześnie, osoby randomizowane do grupy badanej były wyraźnie silniej narażone na powikłania krwotoczne – łącznie poważnie lub drobne krwawienia  wystąpiły u 3,1% pacjentów z grupy badanej, podczas gdy w grupie kontrolnej było to jedynie 1,5% (ryzyko względne 2,13).

Jak widać nowe leki przeciwkrzepliwe, przynajmniej na razie, nie wyprą całkowicie klasycznych doustnych antykoagulantów. Oba badania są ponadto dowodem na zawodność przewidywań naukowców – teoretyczne założenia nie pierwszy i zapewne nie ostatni raz nie znalazły potwierdzenia w badaniu klinicznym.

1. Eikelboom JW et al., Dabigatran versus warfarin in patients with mechanical heart valves. N Engl J Med. 2013 Sep 26;369(13):1206-14.

2. Steg PG et al., Anticoagulation with otamixaban and ischemic events in non-ST-segment elevation acute coronary syndromes: the TAO randomized clinical trial. JAMA. 2013 Sep 18;310(11):1145-55



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