Spironolakton w leczeniu niewydolności serca z zachowaną funkcją skurczową – badanie TOPCAT

Czerwiec 16, 2014  |  Udostępnij  | 

Niewydolność serca z zachowaną funkcją skurczową lewej komory jest chorobą, na którą współczesna kardiologia w zasadzie nie znajduje skutecznej terapii. Dość wspomnieć, że w aktualnych wytycznych Europejskiego Towarzystwa Kardiologicznego (ESC) z 2012 roku przytoczono wyniki jedynie 3 dużych eksperymentów dotyczących leczenia tej jednostki chorobowej, z których żaden nie wykazał jednoznacznej korzyści płynącej z zastosowania badanego preparatu. Nie oznacza to bynajmniej, że zaprzestano poszukiwań środka, który mógłby wpłynąć na poprawę rokowania odległego u tej grupy pacjentów. W poniższym tekście przedstawimy, opublikowane w ostatnim czasie na łamach New England Journal of Medicin, wyniki badania TOPCAT [1], którego celem była ocena skuteczności spironolaktonu w leczeniu niewydolności serca z zachowaną funkcją skurczową lewej komory.
shutterstock_133083467Rekrutację pacjentów do wspomnianego eksperymentu rozpoczęto w 2006 roku, jedocześnie w  6 krajach położonych na terenie obu Ameryk i Europy, a zakończono w styczniu roku 2012. Łącznie na udział w badaniu wyraziło zgodę niemal 3500 pacjentów. Zgodnie z zaprojektowanym protokołem głównymi kryteriami włączenia były objawy niewydolności serca przy frakcji wyrzutowej ≥45%, przy jednoczesnej dobrej kontroli ciśnienia tętniczego i poziomie potasu <5 mmol/l. Wykluczono chorych z ciężkimi chorobami towarzyszącymi m.in. z niewydolnością nerek z GFR <30 ml/min/1,73 m2 i tych, których spodziewany czas przeżycia nie przekraczał 3 lat. Chorych spełniających powyższe warunki, po wyrażeniu przez nich stosownej zgody, losowo przydzielano do grupy badanej i kontrolnej w stosunku 1:1. Pierwsza z wspomnianych grup była leczona spironolaktonem w dawce 45 mg, którą osiągano stopniowo w ciągu pierwszych 4 miesięcy leczenia, pod kontrolą parametrów nerkowych. W tym czasie pacjenci w grupie kontrolnej przyjmowali placebo. Złożony pierwszorzędowy punkt końcowy utworzyły: zgon z przyczyn sercowo-naczyniowych, nagłe zatrzymanie krążenia oraz hospitalizacja z powodu zaostrzenia objawów niewydolności serca. Bezpieczeństwo podawania leku oceniono analizując liczbę przypadków wzrostu kreatyniny oraz częstość występowania hipo i hiperkaliemii. Chorych obserwowano przeciętnie przez ponad 3 lata. Pierwszorzędowy punkt końcowy wystąpił w sumie u 320 osób (18,6%) w grupie leczonej spironolaktonem oraz 351 osób (20,4%) w grupie kontrolnej – ryzyko względne (HR) wyniosło 0,8; jednak wynik nie był istotny statystycznie. Analizując poszczególne składowe punktu końcowego zaobserwowano nieznacznie mniejszą częstość hospitalizacji z powodu niewydolności serca na korzyść spironolaktonu (odpowiednio 12,0% vs. 14,2%; p=0,04). Nie udowodniono natomiast wpływu na zmniejszenie częstości zgonów z przyczyn sercowo-naczyniowych (9,3% vs. 10,2%; p=0,35) oraz na zmniejszenie odsetka przypadków nagłego zatrzymania krążenia (3 vs. 5 zdarzeń; p=0,48). Zgodnie z oczekiwaniami do działań niepożądanych występujących częściej u chorych leczonych spironolaktonem należały hiperkaliemia (18,7% vs. 9,1%) i podwyższenie stężenia kreatyniny (10,2% vs. 7%). Mniejsza był natomiast częstość z jaką obserwowano hipokaliemię (16,2% vs. 22,9%). Ponadto u chorych w grupie badanej o wiele częstsze były przypadki odstawienia leku z powodu ginekomastii.

Podsumowując trzeba przyznać, że spironolakton w żaden sposób nie spełnił pokładanych w nim nadziei. Nie udało się udowodnić jednoznacznie jego wpływu na zmniejszenie śmiertelności, a jednocześnie potwierdzono występowanie typowych dla tego leku działań niepożądanych. W dalszym ciągu chorych z niewydolnością serca z zachowaną frakcją wyrzutową możemy leczyć jedynie pośrednio, poprzez odpowiednią redukcję czynników ryzyka sercowo-naczyniowego.

1. B. Pitt et al., Spironolactone for Heart Failure with Preserved Ejection Fraction, N Engl J Med, 10 April 2014; 370:1383-1392



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