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N Engl J Med. 2008 Dec 18;359(25):2651-62. doi: 10.1056/NEJMoa070570.

Thrombolysis during resuscitation for out-of-hospital cardiac arrest.

Collaborators (197)

Arntz HR, Breckwoldt J, Müller D, Frei U, Nibbe L, Behrens S, Lehmke B, Toursarkissian M, Milz HP, Roeper A, Schniedermeier U, Bode C, Schwab T, Roessler M, Grond S, Meyer O, Böttiger BW, Gries A, Motsch J, Spöhr F, Pahlke K, Reichel J, Reinhart K, Seidenstücker A, Simon R, Corzillius M, Genzwürker H, Viergutz T, Blobner M, Heim M, Altemeyer KH, Flick K, Krieter H, Schlechtriemen T, Dirks B, Weisser F, Martens P, Corne L, Hachimi-Idrissi S, Meert P, Claessens B, de Longueville D, Mols P, Jacques JM, Desruelles D, Sabbe M, Vergnion M, van Belleghem V, Lefebvre P, Stamatakis L, Mazairac G, van Grunsven P, Meursing BT, Keuper W, Verheugt F, Bruning T, van Loenen P, Ent M, Mekel JM, Nierop PR, van Beek GJ, Baubin M, Lederer W, Moritz M, Luger M, Wenzel V, Brunner G, Prause G, Walch H, Wasler A, Weihs W, Chmelizek F, Edtinger S, Franz A, Frauenschuh E, Miller E, Michalski T, Huber K, Kaff A, Malzer R, Geppert A, Riechling N, Riedmüller E, Schreiber W, Herkner H, Seibert F, Enzelsberger B, Slany J, Valentin A, Capellier G, Lapostolle F, Brun-Buisson C, Margenet-Baudry A, Bedos JP, Lambert Y, Goldstein P, Barboteau M, Tazarourte K, Cariou A, Carli P, Eltchaninoff H, Jardel B, Charpentier S, Escallier C, Vikenes B, Ostensvig M, Wik L, Waagsboe NA, Lindner TW, Steen-Hansen JE, Colombi C, Valoti O, Gordini G, Picoco C, Guidetti A, Brandstaetter M, Handschuch A, Landriscina M, Rana S, Annicchiarico M, Bermano F, Panucci P, Fontana G, Ravasi S, Marcora B, Pesenti A, Raimondi M, Sforzini I, Cominotti S, Mare C, Martin Rubi JC, Rosell Ortiz F, Betriu Gibert A, García Alfranca F, Civeira Murillo E, Chacon Manzano C, Martin Montes N, Martin Castro C, Reina Toral A, Corral Torres E, Elvira Garcia JC, Macaya Miguel C, Diaz Carballo C, Garcia Alcantara A, Sanchez Marin J, Lesmes Serrano A, Ruano Marco M, Iniguez Romo A, Munoz Agius F, Rivera N, Svennberg L, Herlitz J, Palm K, Svensson L, Yersin B, Renaud I, Mauri R, Poggi R, Adgey JA, Arntz HR, Bluhmki E, Chamberlain DA, Bode C, Böttiger BW, Wenzel V, Carli PA, Danays T, Meert P, Herlitz J, Yersin B, Pesenti A, Verheugt F, Wik L, Ruano M, Schreiber W, de Latorre FJ, Hacke W, van de Werf F, Ornato JP, Brower RW, Simoons ML, Bluhmki E, Belmans A, Bogaerts K, Bluhmki E, Götz G, Schühly U, Skamira C, Kaye J, Broos K, Goffin L, Luys C, Moreira M, Svärd R, Danays T, von Kummer R, Hacke W.



Approximately 70% of persons who have an out-of-hospital cardiac arrest have underlying acute myocardial infarction or pulmonary embolism. Therefore, thrombolysis during cardiopulmonary resuscitation may improve survival.


In a double-blind, multicenter trial, we randomly assigned adult patients with witnessed out-of-hospital cardiac arrest to receive tenecteplase or placebo during cardiopulmonary resuscitation. Adjunctive heparin or aspirin was not used. The primary end point was 30-day survival; the secondary end points were hospital admission, return of spontaneous circulation, 24-hour survival, survival to hospital discharge, and neurologic outcome.


After blinded review of data from the first 443 patients, the data and safety monitoring board recommended discontinuation of enrollment of asystolic patients because of low survival, and the protocol was amended. Subsequently, the trial was terminated prematurely for futility after enrolling a total of 1050 patients. Tenecteplase was administered to 525 patients and placebo to 525 patients; the two treatment groups had similar clinical profiles. We did not detect any significant differences between tenecteplase and placebo in the primary end point of 30-day survival (14.7% vs. 17.0%; P=0.36; relative risk, 0.87; 95% confidence interval, 0.65 to 1.15) or in the secondary end points of hospital admission (53.5% vs. 55.0%, P=0.67), return of spontaneous circulation (55.0% vs. 54.6%, P=0.96), 24-hour survival (30.6% vs. 33.3%, P=0.39), survival to hospital discharge (15.1% vs. 17.5%, P=0.33), or neurologic outcome (P=0.69). There were more intracranial hemorrhages in the tenecteplase group.


When tenecteplase was used without adjunctive antithrombotic therapy during advanced life support for out-of-hospital cardiac arrest, we did not detect an improvement in outcome, in comparison with placebo. ( number, NCT00157261.)

2008 Massachusetts Medical Society

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