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© Borgis - Postępy Nauk Medycznych 2/2006, s. 1-32
Bronisław Bednarz
Wpływ długotrwałego podawania L-argininy na przebieg zawału serca z uniesieniem odcinka ST
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Effect of long term treatment with L-arginine on the clinical course of acute myocardial infraction with ST segment elevation
Szpital Grochowski, Klinika Kardiologii CMKP
Streszczenie
Wstęp: W ostrym zawale serca dochodzi do długotrwałego upośledzenia funkcji śródbłonka tętnic wieńcowych. Konsekwencją tego zjawiska jest, między innymi, ograniczenie wytwarzania i wydzielania przez komórki śródbłonka tlenku azotu (NO) substancji mającej kluczowe znaczenie dla zachowania przepływu krwi przez tętnice wieńcowe.
W ustroju NO powstaje w wyniku przemian aminokwasu L-argininy.
L-arginina nie była dotychczas stosowana u chorych ze świeżym zawałem serca.
Cel: Celem badań była ocena wpływu długotrwałego podawania L-argininy – substratu dla produkcji NO – na przebieg kliniczny zawału serca z uniesieniem odcinka ST (STEMI).
Metodyka: Badanie było prospektywnym, wieloośrodkowym studium przeprowadzonym metodą podwójnie ślepej próby. Do badania kwalifikowano chorych w wieku powyżej 21 lat z STEMI, przybywających do szpitala w ciągu 24 godzin od początku objawów zawału. Chorych randomizowano do leczenia L-argininą (3x3,0 g na dobę przez 30 dni) lub placebo. Wszyscy chorzy byli ponadto leczeni rutynowo, włącznie z terapią fibrynolityczną, gdy istniały do niej wskazania.
Wyniki: Do badania włączono 792 chorych (średni wiek 64 lata, 550 mężczyzn). 394 chorych otrzymało L-argininę, a 398 placebo.
Powikłania składające się na złożony punkt końcowy (zgon sercowo-naczyniowy, ponowny zawał serca, nawrót spoczynkowego niedokrwienia, skuteczna reanimacja, wstrząs/obrzęk płuc) wystąpiły w ciągu 30 dni u 93 (24%) chorych otrzymujących L-argininę i 104 (27%) chorych otrzymujących placebo (OR 0,63, 95% CI 0,39-1,02, p=0,06).
W podgrupie chorych z hipercholesterolemią (n=226) powikłania te wystąpiły istotnie statystycznie rzadziej w grupie otrzymującej L-arnininę niż w grupie otrzymującej placebo (odpowiednio n=19 [17%] i n=31 [28%], p<0,05).
W podgrupie chorych z przebytym w przeszłości zawałem serca podanie L-argininy statystycznie znamiennie zmniejszyło częstość zgonów z powodów sercowo-naczyniowych w trakcie 6-cio miesięcznej obserwacji (zmarło 5 chorych w grupie argininy i 14 w grupie placebo, p=0,03).
Wnioski: Wyniki badania, będącego pierwszą próbą podania L-argininy w STEMI wskazują na dobrą tolerancję tej substancji.
L-arginina stosowana w dawce 9,0 g na dobę przez 30 dni, ogranicza powikłania STEMI u chorych z hipercholesterolemią i zmniejsza śmiertelność z powodów sercowo-naczyniowych u chorych po przebytym w przeszłości zawale serca.
Summary
Introduction. Acute ischemia and reperfusion lead to prolonged endothelial dysfunction resulting, among others, in reduced release of endothelium-derived relaxing factor – nitric oxide (NO ), which plays the key role in coronary circulation. L-arginine is a substrate for NO synthesis in vascular endothelial cells. To date L-arginine has not been used in acute myocardial infarction.
Aim. The aim of the study was to assess effects of long term treatment with L-arginine on the clinical course of acute myocardial infarction with ST segment elevation (STEMI).
Methods. The study was randomized, multicentre, double-blind, placebo-controlled. Patients of either gender, at the age of > 21 years, were eligible if they presented symptoms of STEMI within 24 hours of onset. The patients were randomized to receive L-arginine (3.0 g t.i.d. for a total period of 30 days) or placebo on top of routine therapy including fibrinolysis if indicated.
Results. 792 patients (mean age 64 years, 550 men) were randomized to oral L-arginine (n=394) or placebo (n=398). The end point which was the composite of 30 day cardiovascular death, reinfarction, successful resuscitation, shock/pulmonary edema or recurrent myocardial ischemia occurred in 24% patients treated with L-arginine and 27% with placebo (OR 0.63, 95% CI 0.39-1.02, p=0.06). In 226 patients with hyperlipidemia the end point was observed less frequently in the L-arginine group than in the placebo group (19 [17%] vs 31 [28%], p<0.05). In the subgroup of 105 patients with previous myocardial infarction cardiovascular death occured less frequently during 6 months follow up in the patients treated with L-arginine (5 in L-arginine group and 14 in the placebo group, p=0.03).
Conclusion. This study, which is the first to study L-arginine in STEMI, showed that oral L-arginine supplementation was well tolerated. L-arginine in a dose of 9.0 g daily for 30 days reduces the number of major clinical events during 30 days follow up in the group of patients with hyperlipidemia and reduces the number of cardiovascular deaths in the group of patients with previous myocardial infarction.
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otrzymano: 2005-04-10
zaakceptowano do druku: 2005-11-20

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