Badanie REMINDER – poszukiwanie nowych zastosowań dla eplerenonu

Maj 9, 2014  |  Udostępnij  | 

Blokery receptora aldosteronowego (ARB) – eplerenon i spironolakton – są lekami stosowanymi w kardiologii u pacjentów z przewlekłą niewydolnością serca.  Według obecnie obowiązujących wytycznych Europejskiego Towarzystwa Kardiologicznego (ESC) preparaty te powinny być dołączone do terapii jako trzeci lek (do inhibitora konwertazy angiotensyny (ACEI) i B-blokera) u wszystkich chorych w II-IV klasie hemodynamicznej wg NYHA, gdy frakcja wyrzutowa lewej komory (EF) utrzymuje się na poziomie ≤35%. Skuteczność ARB  była udowadniana w wielu randomizowanych badaniach klinicznych m.in. w badaniu EMPHESUS, w którym eplerenon  włączony przed upływem 14 dni od zawału serca (MI) u chorych z EF<40% zmniejszał względne ryzyko zgonu z przyczyn sercowo-naczyniowych aż o 15%. Zauważono jednocześnie, że chorzy, u których leczenie rozpoczynano pomiędzy 3 a 7 dniem po zawale, mieli lepsze rokowanie niż pacjenci, u których eplerenon włączono w drugim tygodniu po MI. Czy wobec tego blokery receptora aldosteronu włączone odpowiednio szybko mogą przynieść korzyść tym spośród chorych po przebytym zawale, którzy nie mają objawów niewydolności serca?
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W ostatnich dniach, na razie jedynie na stronie European Heart Journal , ukazały się wyniki badania, którego autorzy próbowali odpowiedzieć na to pytanie. Zaprojektowany przez nich protokół eksperymentu przewidywał rozpoczęcie podawania eplerenonu w dawce 25-50mg/d u pacjentów bez wcześniejszego wywiadu niewydolności serca, w pierwszych 24 h po zawale z uniesieniem odcinka ST (STEMI). Na udział w badaniu REMINDER[1] (taką nazwę nadano projektowi) zgodę wyraziło 1012 pacjentów po przebytym STEMI. Chorym losowo przydzielonym do grupy badanej podawano eplerenon, natomiast w grupie kontrolnej stosowano placebo. Na założony pierwszorzędowy punkt końcowy składały się: zgon z przyczyn sercowo-naczyniowych, ponowna hospitalizacja lub wydłużenie pobytu w szpitalu z powodu niewydolności serca, spadek EF<40% lub podniesione poziomy BNP lub NT-proBNP. Średni okres obserwacji wyniósł 10,5 miesiąca. W tym czasie co najmniej jedno z wymienionych zdarzeń odnotowano u 92 pacjentów (18,2%) w grupie badanej oraz 149 chorych (29%) „leczonych” placebo (ryzyko względne (HR) 0,58; p<0,0001). Po dokładniejszej analizie okazało się, że obserwowana różnica wiąże się głównie z wpływem eplerenonu na obniżenie stężenia BNP/NT-proBNP, natomiast dla żadnej z pozostałych składowych pierwszorzędowego punktu końcowego nie udało się uzyskać istotności statystycznej. Odsetek działań niepożądanych był zbliżony w obu grupach. Szczególnie ważny efekt uboczny leczenia blokerami receptora aldosteronu – hiperkaliemia – występował częściej wśród chorych leczonych tymi właśnie lekami, jednak różnica nie była istotna statystycznie (5,6% vs. 3,2%; p=0,09). Z drugiej strony hipokaliemia występowała znamiennie częściej w grupie kontrolnej (1,4% vs. 5,6%; p<0,001).

 

Podsumowując można stwierdzić, że opisywane badanie nie odpowiedziało jednoznacznie na pytanie, czy wczesne włączenie eplerenonu u pacjentów po STEMI, ale bez niewydolności serca może poprawiać ich rokowanie. Przy stosunkowo niewielkiej, tysiąc-osobowej próbie wykazano znamienny wpływ badanego leku na poziom BNP/NT-proBNP, jednak nie osiągnięto celu głównego – istotnego wpływu na redukcję śmiertelności czy poważnych zdarzeń sercowo-naczyniowych. Niewątpliwie jest to zachęta do powtórzenia badania na o wiele większej grupie chorych.

 

1. G Montalescot et al.,  Early eplerenone treatment in patients with acute ST-elevation myocardial infarction without heart failure: The Randomized Double-Blind Reminder Study, Eur Heart J; published online:  29 April 2014


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benzodiazepines b e nz o d i A Z e p e nz bipolar disorder b i P O l a r d i s O Rd e r borderline personality B O Rd e rl i n p e rs o N A L i t e bulimia nervosa b u L E m e a n e rV O s a cannabis K A n a bis catatonia k a t a T O N e a claustrophobia klawstr o F O b e a cognitive behavioral therapy K O Gn i t i v b e H A Vy o r a l TH E R a p e compulsion k o mP U Lsh u n conversion disorder k o nV E Rzh u n d i s O Rd e r PSYCHIATRY TERM PRONUNCIATION MEANING cyclothymia s i kl o TH I m e a defense mechanism d e F E NS m e k a nN I ZM delirium d e L I R e u m delirium tremens d e L I R e u m TR E m e nz delusion d e LOOzh u n dementia d e M E Nsh e a depression d e PR E sh u n dissociative disorder d i sS O sh e a t i v d i s O Rder dysphoria d i sF O R e a dysthymia d i sTH I m e a ego E g o electroconvulsive therapy e l e ktr o k o nV U Ls i v TH E R a p e euphoria u F O R e a euthymic u TH I m i k exhibitionism e ks i B I SH u n i zm family therapy F A M i l e TH E R a p e fetishism F E T i sh i zm free association fr e a s o sh e A sh u n fugue f u g gender identity disorder G E Nd e r i D E Nt i t e d i s O Rd e r group therapy groop TH E R a p e hallucination h a loos i N A sh u n hallucinogen h a LOOs i n o j e n histrionic personality h i str e O N i k p e rs o n A L i t e hypnosis h i pN O s i s hypochondriasis h i p o k o nDR I a s i s hypomania h i p o M A n e a iatrogenic i a tr o J E N i k id i d PSYCHIATRY TERM PRONUNCIATION MEANING insightoriented therapy I Ns i t O R e e nt e d TH E R a p e kleptomania kl e pt o M A n e a labile L A b i l lithium L I TH e u m mania M A n e a mental M E Nt a l mood disorders mood d i s O Rd e rz mutism M U t i zm narcissistic personality n a rs i S I St i k p e rs o N A L i t e neuroleptic drug noor o L E Pt i k dr u g neurotransmitter noor o TR A NZm i t e r obsession o bS E SH u n obsessivecompulsive disorder o bS E S i v c o mP U Ls i v d i s O Rd e r opioids O p e o ydz paranoia p a r a N O Y a paranoid personality P A R a n o yd p e rs o N A L i t e paraphilia p a r a F I L e a pedophilia p e d o F I L e a personality disorders p e rs o N A L i t e d i s O Rd e rz pervasive developmental disorders p e rV A S i v d e V E L o pm e nt a l d i s O Rd e rz phenothiazines f e n o TH I a z e nz phobia F O b e a play therapy pl a TH E R a p e posttraumatic stress disorder p o sttrawM A T i k str e s d i s O Rd e r projective test pr o J E Kt i v t e st psychiatrist s i K I a tr i st psychiatry s i K I a tr e psychoanalysis s i k o a N A L i s i s psychodrama s i k o DR A m a PSYCHIATRY TERM PRONUNCIATION MEANING psychogenic s i k o J E N i k psychologist s i K O L o j i st psychopharmacology s i k o f a rm a K O L o j e psychosis s i K O s i s psychosomatic s i k o s o M A T i k psychotherapy s i k o TH E R a p e pyromania p i r o M A n e a reality testing r e A L i t e T E St i ng repression r e PR E sh u n schizoid personality SK I Z o yd or SK I Ts o yd p e rs o N A L i t e schizophrenia sk i z o FR E n e a sedatives S E D a t i vz sexual disorders S E X u a l d i s O Rd e rz sexual masochism S E X u a l M A S o k i zm sexual sadism S E X u a l S A d i zm somatoform disorders s o M A T o f o rm d i s O Rd e rz substancerelated disorder S U Bst a ns r e L A t e d d i s O Rd e r superego s u p e r E g o supportive psychotherapy s u P O Rt i v s i k o TH E R a p e tolerance T O L e r a ns transference tr a nsF U R e ns transvestic fetishism tr a nsV E St i k F E T i sh i zm tricyclic antidepressants tr i S I Kl i k a nt i d e PR E s a ntz voyeurism V O Yy e r i zm xenophobia z e n o F O b e a PSYCHIATRY REVIEW SHEET Write the meanings of the word parts in the spaces provided and test yourself.Other causes include amyloid angiopathy anticoagulantantithrombolytic use brain tumors and AV malformations [url=http://duro-k.com]online pharmacy[/url] CHF d.More therapy is usually needed either in the form of more chemotherapy or a bone marrow transplant.Complicationsclear fluid 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