A COMPARISON OF RECOMBINANT HIRUDIN WITH HEPARIN FOR THE TREATMENT OFACUTE CORONARY SYNDROMES

Authors
TOPOL EJ CALIFF R GRANGER C VANDEWERF F AYLWARD P SIMES J COL J ARMSTRONG P VAHANIAN A NEUHAUS K RUTSCH W ARDISSINO D SIMOONS M WHITE H BETRIU A EMANUELSSON H PFISTERER M BEATT K BATES E CHESEBORO J ELLIS S FUSTER V GIBLER W GORE J GUERCI A HOCHMAN J HOLMES D KLEIMAN N MORRIS D OHMAN M PHILLIPS H WEAVER D LEE K WOODLEAF L MILLER G BAHR R WORLEY S SCHRADING W GILCHRIST I IBARRA J KRISHNASWAMI V NYGAARD T DAGEFORDE D PUMA J PALMERI S ROSING D DALE H BOYEK T MORRICE B WEINBERG S NOBLE W VANGILDER J OTOOLE J JESSE R LOSS D WERTHEIMER J FERRARI D SANTER M STRAHAN N SCHAEFFER J AVEINGTON M MILLER R EICH D VROBEL T KERIEAKES D SHARMA S BECKWITH W MICALE P POLINSKI W GOODFIELD P PARASCHOS A CHANDLER A TALLEY J MORSE H SHERIDAN F SILVERMAN M BAGA V WARE J SEAGLE R MADDOX W SCHRANK J GAINEY P MORRIS D IWAOKA R SCHNEIDER R INGRAM R HANGER K LANE G BEESON W WILLIAMS D BEASLEY C SPRIGGS D SCHLANT R SULLEBARGER J SMITH J MISHKEL D WILLIAMS C GIBBS K HEARON B GONZALES M SHEIKH K DEDONIS J LONG T POPIO K JAMAL N LAMBREW C LABIB S VORCHHEIMER D WEISS R MERCADANTE N GUEREI A RASHKOW A BALLELI L GACIOCH G NILES N SEIDENSTEIN H HOLLANDER G WALLACH R KHAN A GRAHAM S SIMONS A WARD H PARKES R WATKINS M DELUCCIA W URBACH D GRODMAN R MCCORD D BLEIBERG M CORBELLI J PEPE A ZWERNER P PINSKY L PETROVICH L LINDENBERG B THERRIEN M SANDS M ROSENFELD A SHEIKH S RIBA A HANOVICH G SWENSON L HOLLAND K SCHMIDT P BESLEY D HESSION W FERRIGNI F MEYERS D DUVERNOY W ABRAMOWITZ B STOMEL R BECKER J MOOSS A THOMPSON J CALLI L PENILLA A MCCRISKIN J MILLSAPS R HEINSIMER J PFEFFERKORN D SADDIN M FINTEL D HARNER R KOPECKY S ANDRES P COOK L WEFALD F VANDERLAAN R LOVE J ZANDS M SANTOLIN C ARNOLD A OATFIELD R JAEGER K DEAN E SWENSON R LANCASTER L RASKIN S FEHRENBACHER G LOMBARDO T STRUNK B PERRY J LAI P ROWE W SYMKOVIAK G LEE H KWEE H WOOLBERT S MILLER R KAPLAN J TITUS B WOLFE C CISLOWSKI D BERNDT T WHITE R BROWN D HILL D HUI G SPIEGEL R WESLEY G MATTERN A LAPIN E STERN M KRAUS M OLSON H SCOTT R MACKENZIE B HUI W ROTH S GOODE E BURTON J SENARATNE M TRABOULSI M GREENWOOD P MORGAN C ERVIN F MCDOWELL J LEFKOWITZ C SAUVE M TUREK M FINNIE K KURUVILLA G LANGE A CHARLES J KELLS C VIZEL S BAILLIE H SAHAY B ROTH D LUBELSKY B JABLONSKY G LESOWAY R KOWK K MACMILLAN C ADELMLAN A LABINAZ M GUAGLIUMI G BRANZI A GALVANI M MAFRICI A SAVONITTO S FORNARO G COLOMBI E ZANUTTINI D OTTANI F CAVALLINI C CAMERINI F REPETTO S VASSANELLI C ROVELLI E POLESE A POLITI A CAPUCCI A MAMBELLI M SABATE X MASIA R BESCOS LL SENDON JL JODAR L RODRIQUEZLLORIAN A MARTINLUENGO C SAENZ L FERNANDEZAVILES F FROUFE J LOMAOSORIO A BAYON J JEFFREY I NELSON G WALSH W LEITCH J CAMPBELL T HEALEY J OWENSBY D RAMSEY D GRIGG L FERDERMAN J NEWMAN R STRICKLAND J LIM P COUNSELL J CROSS D GARRAHY P COVERDALE S BETT N ARONCY G BROWN M SIMMONS G HOROWITZ J THOMPSON P HOCKINGS B HENDRICKS R THOMSON A RANKIN R BOUMA H COZYNSEN L STOLWIJK P DROST H VANKALMTHOUT P ENGBERS J WESTENDORP P VOORBURG J VEERHOEK M PAOHAN T BOGERIJEN L MISIER AR BOSKER H SMITS W TAN T CASTADOT M INSTALLE E DEMEESTER A BOLAND J LEGRAND V VANWELDEN J PIRENNE B EMMERECHTS C BEEUWSAERT R THIELS H BECKERS J LESSELIERS H POPEYE R QUIRET J MARONI J FARAH B ETIENNE Y FUNCK F THANK XT KHALIFE K LECLERCQ F VITOUX B COHEN A VACHERON A BARREAU D SIMON R KREFT H DITTER H ZEIHER A WEIZNER M WACKER R MARBACH M NAST H MEYERHOFMANN H SCHMITZHUBNER U BODE M MAISCH B TOPP H RUTSCH W LOLLGEN H WILLIAMS M DURHAM D BRUNS B HAYES D LESLIE P HART H IKRAM H MANN S KIRK A JARDINE D RANKIN R AUDEAU M ANANDARAJA S COOPER I HOGAN J HACKETT D TRAVILL C BRIDGON G BURRELL C DEBELDER M ROZKOVEC A KOONER J JAMES M GARCIA E RISENFORS M PFISTERER M BAUR H URBAN P MOCETTI T ANGEHRN W BERTEL O AMANN F
Citation
Ej. Topol et al., A COMPARISON OF RECOMBINANT HIRUDIN WITH HEPARIN FOR THE TREATMENT OFACUTE CORONARY SYNDROMES, The New England journal of medicine, 335(11), 1996, pp. 775-782
Citations number
33
Categorie Soggetti
Medicine, General & Internal
Journal title
The New England journal of medicine → ACNP
ISSN journal
00284793
Volume
335
Issue
11
Year of publication
1996
Pages
775 - 782
Database
ISI
SICI code
0028-4793(1996)335:11<775:ACORHW>2.0.ZU;2-C
Abstract
Background Thrombin has a pivotal role in the pathogenesis of acute co ronary thrombosis. We compared the clinical efficacy of a potent, dire ct thrombin inhibitor, recombinant hirudin, with that of heparin (an i ndirect antithrombin agent) in patients with unstable angina or acute myocardial infarction. Methods At 373 hospitals in 13 countries, 12,14 2 patients with acute coronary syndromes were randomly assigned to 72 hours of therapy with either intravenous heparin or hirudin. Patients were stratified according to the presence of ST-segment elevation on t he base-line electrocardiogram (4131 patients) or its absence (8011 pa tients), with the latter characteristic considered to indicate unstabl e angina or non-Q-wave myocardial infarction. Results At 24 hours, the risk of death or myocardial infarction was significantly lower in the group assigned to hirudin therapy than in the group assigned to hepar in (1.3 percent vs. 2.1 percent, P = 0.001). The primary end point of death or nonfatal myocardial infarction or reinfarction at 30 days was reached in 9.8 percent of the heparin group as compared with 8.9 perc ent of the hirudin group (odds ratio for the risk of the end point in the hirudin group, 0.89; 95 percent confidence interval, 0.79 to 1.00; P = 0.06), The predominant effect of hirudin was on myocardial infarc tion or reinfarction and was not influenced by ST-segment status. Ther e were no significant differences in the incidence of serious or life- threatening bleeding complications, but hirudin therapy was associated with a higher incidence of moderate bleeding (8.8 percent vs. 7.7 per cent, P = 0.03), Conclusions For acute coronary syndromes, recombinant hirudin provided a small advantage, as compared with heparin, princip ally related to a reduction in the risk of nonfatal myocardial infarct ion. The relative therapeutic effect was more pronounced early (at 24 hours) but dissipated over time, The small benefit was consistent acro ss the spectrum of acute coronary syndromes and was not associated wit h a greater risk of major bleeding complications. (C) 1996, Massachuse tts Medical Society.