MASCC/ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy

BACKGROUND Mucositis is a highly significant, and sometimes dose-limiting, toxicity of cancer therapy. The goal of this systematic review was to update the Multinational Association of Supportive Care in Cancer and International Society of Oral Oncology (MASCC/ISOO) Clinical Practice Guidelines for mucositis. METHODS A literature search was conducted to identify eligible published articles, based on predefined inclusion/exclusion criteria. Each article was independently reviewed by 2 reviewers. Studies were rated according to the presence of major and minor flaws as per previously published criteria. The body of evidence for each intervention, in each treatment setting, was assigned a level of evidence, based on previously published criteria. Guidelines were developed based on the level of evidence, with 3 possible guideline determinations: recommendation, suggestion, or no guideline possible. RESULTS The literature search identified 8279 papers, 1032 of which were retrieved for detailed evaluation based on titles and abstracts. Of these, 570 qualified for final inclusion in the systematic reviews. Sixteen new guidelines were developed for or against the use of various interventions in specific treatment settings. In total, the MASCC/ISOO Mucositis Guidelines now include 32 guidelines: 22 for oral mucositis and 10 for gastrointestinal mucositis. This article describes these updated guidelines. CONCLUSIONS The updated MASCC/ISOO Clinical Practice Guidelines for mucositis will help clinicians provide evidence-based management of mucositis secondary to cancer therapy. © 2014 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society

DETERMINANTS OF 6-MONTH MORTALITY IN SURVIVORS OF MYOCARDIAL-INFARCTION AFTER THROMBOLYSIS - RESULTS OF THE GISSI-2 DATA-BASE

none647Background. Current knowledge of risk assessment in survivors of myocardial infarction is largely based on data gathered before the advent of thrombolysis. It must be determined whether and to what extent available information and proposed criteria of prognostication are applicable in the thrombolytic era. Methods and Results. We reassessed risk prediction in the 10 219 survivors of myocardial infarction with follow-up data available (ie, 98% of the total) who had been enrolled in the GISSI-2 trial, relying on a set of prespecified variables. The 3.5% 6-month all-cause mortality rate of these patients compared with the higher value of 4.6% found in the corresponding GISSI-1 cohort, originally allocated to streptokinase therapy, indicates a 24% reduction in postdischarge 6-month mortality. On multivariate analysis (Cox model), the following variables were predictors of 6-month all-cause mortality: ineligibility for exercise test for both cardiac (relative risk [RR], 3.30; 95% confidence interval [CI], 2.36-4.62) and noncardiac reasons (RR, 3.28; 95% CI, 2.23-4.72), early left ventricular failure (RR, 2.41; 95% Cl, 1.87-3.09), echocardiographic evidence of recovery phase left ventricular dysfunction (RR, 2.30; 95% CI, 1.78-2.98), advanced (more than 70 years) age (RR, 1.81; 95% Cl, 1.43 -2.30), electrical instability (ie, frequent and/or complex ventricular arrhythmias) (RR, 1.70; 95% Cl, 1.32-2.19), late left ventricular failure (RR, 1.54; 95% Cl, 1.17-2.03), previous myocardial infarction (RR, 1.47; 95% CI, 1.14-1.89), and a history of treated hypertension (RR, 1.32; 95% Cl, 1.05-1.65). Early post-myocardial infarction angina, a positive exercise test, female sex, history of angina, history of insulin-dependent diabetes, and anterior site of myocardial infarction were not risk predictors. On further multivariate analysis, performed on 8315 patients with the echocardiographic indicator of left ventricular dysfunction available, only previous myocardial infarction was not retained as an independent risk predictor. Conclusions. A decline in 6-month mortality of myocardial infarction survivors, seen within 6 hours of symptom onset, has been observed in recent years. Ineligibility for exercise test, early left ventricular failure, and recovery-phase left ventricular dysfunction are the most powerful (RR, >2) predictors of 6-month mortality among patients recovering from myocardial infarction after thrombolysis. Qualitative variables reflecting residual myocardial ischemia do not appear to be risk predictors. The lack of an independent adverse influence of early post-myocardial infarction angina on 6-month survival represents a major difference between this study and those of the prethrombolytic era.noneVOLPI A; DEVITA C; FRANZOSI MG; GERACI E; MAGGIONI AP; MAURI F; NEGRI E; SANTORO E; TAVAZZI L; TOGNONI G; FERUGLIO GA; LOTTO A; ROVELLI F; SOLINAS P; TAVAZZI L; TOGNONI G; BRUNO M; CAPPELLO T; COPPINI A; FINCATI F; MANTOVANI G; PANGRAZZI J; POGNA M; TURAZZA FM; ANSELMI M; BARBONAGLIA L; BIGI R; CAVALLI A; FRIGERIO M; GIORDANO A; GUALTIEROTTI C; TORTA D; CAROLA R; GIORDANO F; BARLOTTI R; LOPARCO G; VIGLINO GL; RUGGERI G; GIAMUNDO L; DANESI A; PACIARONI E; GAMBINI C; URBANO G; PURCARO A; FRANCESCONI M; FIGLIOLIA S; CANNONE M; ANTOLINI R; DEVOTI G; CRISTALLINI P; PORCIELLO PI; TEONI P; BURALI A; ZUCCONELLI V; DEMATTEIS C; IERVOGLINI A; SCATASTA M; AMABILI S; CARATTI CA; ZOLA G; FERRAGUTO P; SALICI G; CENTARO A; ROTIROTI D; GENOVESE M; GINEVRINO P; DAMATO N; ALTAMURA CM; COLONNA L; CASTELLANETA G; BOVENZI F; MESSINA D; GALANTINO A; CAMPOREALE N; CUCCHINI F; CAMPOSTELLA L; MALACRIDA R; GENONI M; PELLEGRINI P; BRIDDA A; RIGGI L; ACONE L; MOSCATIELLO G; BRUNO A; INVERNIZZI G; TESPILI M; GUAGLIUMI G; CASARI A; ALBANO T; TOMASSINI B; TORTA D; DIBIASE G; SCARAMUZZINO G; RUGGERO S; BRACCHETTI D; DECASTRO U; FULVI M; BRAITO E; ERLICHER A; OBERLECHNER W; GAGLIARDI RS; BIGHIGNOLI L; BONIZZATO G; RIZZI GM; SCAZZINA L; PERRINI A; STRANEO G; STRANEO U; SCIRE A; VERRIENTI A; GUADALUPI M; STORELLI A; ZUCCA L; DABUSTI M; ALBONICO B; DEPETRA V; TABACCHI GC; SCERVINO R; MEREU D; MAXIA P; BIANCO A; CRABU E; MANGIAMELI S; CENTAMORE G; MALFITANO D; AMICO C; VANCHERI F; SANTOPUOLI G; BALDINI F; PANTALEONI A; CONTESSOTTO F; TERLIZZI R; MERIGHI A; TURCHI E; TEGLIO V; PIGNATTI F; PEZZANA A; GOZZOLINO G; GIGLIO M; PETTINATI G; IEVA M; CIRICUGNO S; CORREALE E; ROMANO S; DIFUCCIA A; CASTELLANO B; NATALE A; CERNETTI C; CELEGON L; CANDELPERGHER G; ARIENZO F; RUSSO F; DEVIVO L; MAY L; ACHILLI G; BLASI A; SORRENTINO F; DATO A; GALLONE P; PALUMBO C; DELLAMONICA R; PAGANO L; ALBERTI A; ORSELLI L; DEPONTI C; PARMIGIANI ML; FERRARI M; ACITO P; BUSI F; DELLAVITTORIA G; BELLET C; BORTOLINI F; ROSSI A; CORONA C; BONDI S; NICCOLINI D; GAMBERI G; ARCURI G; MAIOLINO P; CARROZZA A; DELIO U; CAPRETTI G; MARINONI C; GUASCONI C; SONNINO S; PAGLIEI M; FERRARI G; LOMBARDI R; AGNELLI D; DERINALDIS G; CALCAGNILE A; SIGNORELLI S; BENDINELLI S; LUSETTI L; MOLLAIOLI M; COSMI F; PLASTINA F; VENNERI N; FERACO E; CATELLI P; POLUZZI C; DISTANTE S; BIANCHI C; COPPETTI S; ZAMPAGLIONE G; GATTO C; ZURLO R; USLENGHI E; MARGARIA F; MILANESE U; LOMANTO B; ZIACCHI V; RIVA D; BERTOCCHI P; TIRELLA G; DAULERIO M; SAURO G; BINI A; MAZZONI V; POGGI P; MARESTA A; JACOPI F; PATRONCINI A; PUPITA F; GAGGI S; FRAUSINI G; ANTONIOLI GE; MALACARNE C; CODECA L; CAPPATO R; ANDREOLI L; VARACCA S; BUIO E; FAZZINI PF; PUCCI P; SARRO F; VERGASSOLA R; BARCHIELLI M; DEMATTEIS D; CARRONE M; BRUNOZZI LT; MENICONI L; LIBERATI R; RADOGNA M; TALLONE M; CONTE R; IERI A; ZIPOLI A; SANSONI M; CANZIANI R; GUIDALI P; CRISTALLO E; MARIELLO F; MUZIO L; BENVENUTO MR; BALDINI MR; VECCHIO C; CHIARELLA F; FALCIDIENO M; CECCHI A; GIULIANO G; SEU V; PERUGINI P; TOSELLI A; BASSO F; CORTI E; ROSSI P; DELFINO R; CAPONNETTO S; GNECCO G; GHIGLIOTTI G; PENNESI A; LOMBARDI G; RUGGIERI A; BERTOLO L; SLOMP L; LANZETTA T; MAZZARONE L; CRESTI A; BELLODI G; ZUARINI AM; VENERI L; PARCHI C; GIOVANELLI N; NEGRONI S; DETHOMATIS M; BARGHINI A; MARINO E; RICCI D; LEMME P; DIGIACOMO U; AQUARO G; RONZANI G; OTTELLO B; VONTI V; MORETTI S; PALERMO R; MARSILI P; SIDERI F; RAGAZZINI G; GRAMENZI S; BATTISTINI S; DIODATO T; VALERIO A; TUCCI C; DEPASQUALE B; GELFO PG; BERTULLA A; BOLLINI R; DEMARCHI E; BACCA F; DEGIORGI V; LOCATELLI V; SAVOIA MT; FERRACINI C; BARBARESI F; COTOGNI A; FRANCO G; ROMANO S; PASSONI F; DURBANO M; MORETTI G; PEROTTI S; CAPRETTI M; DELBENE P; CASCONE M; BALDINI U; ORLANDI M; ODDONE A; CAIZZI V; MASINI G; LAZZARI M; BALLERINI B; BOZZI L; MOCETTI T; BERTOLINI A; PASOTTI E; SANGUINETTI M; MANTOVANI R; TOGNOLI T; MAGGI A; TUSA M; CAMERONI E; GUERRA GP; REGGIANI A; REDAELLI S; GIUSTI S; TANTALO L; RIZZI A; DIGIOVANNI N; GUZZO V; GABRIELE M; COLOMBO G; ALBERZONI A; SALVIOLI G; GALFETTI F; DOVICO E; BELLUZZI F; GOLA E; CASELLATO F; LECCHI G; CONSOLO F; SACCA CB; CONSOLO A; PICCOLO E; GASPARINI G; DEVITA C; ALBERTI A; MASSA D; BELLI C; DOSSENA MG; CORSINI C; SANNA GP; AZZOLLINI M; TRUAZZA F; LOTTO A; NADOR F; DEMARTINI M; BOZZI G; SEREGNI R; PASTINE I; MORPURGO M; CASAZZA F; REGALIA F; MAGGIOLINI S; RIGO R; PANCALDI S; POZZETTI D; PASCOTTO P; FRANCESCHI L; DAINESE F; MELINI L; CAPPELLI C; BERNARDI C; PALMIERI M; BORGIONI L; ZILIO G; SANDRI R; ALITTO F; MASARO G; VALAGUSSA F; SCHIAVINA R; RAVESI D; DANIELLO L; PIANTADOSI FR; BARRA P; ROMEO D; MININNI N; SEVERINO S; MOSTACCI M; CASTELLARI M; BANDA D; ROLANDI R; VILLA WD; CARBONE V; ALLEGRI M; FASCIOLO L; PITTALIS M; MUREDDU V; SORO F; DELEDDA MG; MARRAS E; MARCHI SM; DELUCA C; MANETTA M; VOLTA SD; SPERANDEO V; DONZELLI M; VITRANO MG; GERACI E; PITROLO F; LAMONICA S; BELLANCA G; MESSINA G; MIRTO U; RAINERI A; TRAINA M; DIBENEDETTO A; RIBAUDO E; DIFRANCESCO M; RONCHITELLI R; CARONE M; DIGREGORIO D; DIPAOLO G; PASQUALE M; COREA L; COCCHIERI M; ALUNNI G; PAPI L; CHIRIATTI G; LUPETTI M; GAZZOLA U; ARRUZZOLI S; VILLANI GQ; MELLINI M; MADRUZZA L; PIAZZA R; MICHELI G; FRANCHINI C; BECHI S; MARTINES C; MARCHESE D; GABBIA G; BIGALLI A; CIUTI M; CABANI E; DELCITERNA F; ALFIERI A; CHITI M; LONGHINI J; CODELUPPI P; NEGRELLI M; ZANUTTINI D; NICOLOSI GL; MARTIN G; PETRELLA A; BARDAZZI L; BIANCO GA; CELLAMARE G; GIANNELLI F; LICITRA G; LICITRA R; LETTICA GV; TUMIOTTO G; BELLANTI G; BOSI S; CASALI G; MONDUCCI I; BARONE A; PARENTI F; HEYMAN J; COZZI E; BALDACCI G; BACCOS D; BRIGHI F; DESANCTIS A; BOCK R; PALMIERI M; ROSSI F; AMATI P; SEMPRINI P; NARDELLI A; BOTTERO G; VARTOLO C; MILAZZOTTO F; DICROCE G; DIMARIO F; ANGRISANI G; AZZOLINI P; NEJA CP; MANZOLI U; ROSSI E; TRANI C; MASINI V; SEBASTIANI F; TOPAI M; BORGIA MC; LUCIANI C; FERRI F; DEPAOLA D; CAPURSO S; TUGNOLI F; VETTA C; ALTIERI T; BORZI M; VISCOMI A; STRIANO U; SALITURI S; ZONZIN P; FIORENCIS R; BADIN A; RAVERA B; BALDI C; SILVESTRI F; ALLEMANO P; REYNAUD S; SANSON A; MILANI L; DESIMONE MV; RUSSO A; VILLELLA A; GRAZINI M; AMIDEI S; ANSELMI L; PICCANICOLINO R; MASCELLI G; TAGLIAMONTE A; MESSINA V; TEDESCHI C; BOSSI M; BISIOLI M; TACCHI G; PAGNI G; VIVALDI F; IBBA GV; SANNIA L; PEDRAZZINI F; BAGNI E; FABII S; ALVINO A; ANTONIELLI E; DORONZO B; MARTINENGO E; BECCHI G; SALMOIRAGHI A; DIGIOVANNA F; CARAMANNO G; CAPORICCI D; BRUN M; GIANI P; FERRARIO G; PECI P; RONCONI G; SKOUSE D; BIANCHI C; GIUSTINIANI S; CUCCHI GF; TAVASCI E; SILVERII A; MARCELLINI G; SPECA G; STANISCIA D; CIMINO A; SERAFINI N; DEBONIS P; CERRUTI P; BAZZUCCHI M; DALPRA F; SPEROTTO C; MOLE GD; BARBANO G; POMARI F; GASCHINO G; PARIGI A; GANDOLFO N; RONDONI F; BRUSCA A; DILEO M; GOLZIO PG; ABRATE M; SCLAVO MG; ROCCI R; POGGIO G; GIANI S; CUZZUCREA D; BRASCHI GB; SCIACCA R; SAMMARTANO A; FURLANELLO F; BRAITO G; CUZZATO V; TOTIS O; FAURETTO F; LEO F; GALATI A; PALMA P; CAMERINI F; MORGERA T; BARBIERI L; FERUGLIO GA; SLAVICK GA; FRESCO C; CUDA A; SARNICOLA P; ARZILLO P; BINAGHI G; MACCHI G; CALVERI G; DIMARCO G; LEVANTESI G; PANERAI C; CATURELLI G; FACCHIN L; SARTORE G; ZARDINI P; MARINO P; CARBONIERI E; NAVA S; MAZZINI C; NAVA R; SERRA N; SASSARA M; NICROSINI F; GANDOLFI P; BERGOGNONI G; BALLESTRA AM; VIOLO CVOLPI A; DEVITA C; FRANZOSI MG; GERACI E; MAGGIONI AP; MAURI F; NEGRI E; SANTORO E; TAVAZZI L; TOGNONI G; FERUGLIO GA; LOTTO A; ROVELLI F; SOLINAS P; TAVAZZI L; TOGNONI G; BRUNO M; CAPPELLO T; COPPINI A; FINCATI F; MANTOVANI G; PANGRAZZI J; POGNA M; TURAZZA FM; ANSELMI M; BARBONAGLIA L; BIGI R; CAVALLI A; FRIGERIO M; GIORDANO A; GUALTIEROTTI C; TORTA D; CAROLA R; GIORDANO F; BARLOTTI R; LOPARCO G; VIGLINO GL; RUGGERI G; GIAMUNDO L; DANESI A; PACIARONI E; GAMBINI C; URBANO G; PURCARO A; FRANCESCONI M; FIGLIOLIA S; CANNONE M; ANTOLINI R; DEVOTI G; CRISTALLINI P; PORCIELLO PI; TEONI P; BURALI A; ZUCCONELLI V; DEMATTEIS C; IERVOGLINI A; SCATASTA M; AMABILI S; CARATTI CA; ZOLA G; FERRAGUTO P; SALICI G; CENTARO A; ROTIROTI D; GENOVESE M; GINEVRINO P; DAMATO N; ALTAMURA CM; COLONNA L; CASTELLANETA G; BOVENZI F; MESSINA D; GALANTINO A; CAMPOREALE N; CUCCHINI F; CAMPOSTELLA L; MALACRIDA R; GENONI M; PELLEGRINI P; BRIDDA A; RIGGI L; ACONE L; MOSCATIELLO G; BRUNO A; INVERNIZZI G; TESPILI M; GUAGLIUMI G; CASARI A; ALBANO T; TOMASSINI B; TORTA D; DIBIASE G; SCARAMUZZINO G; RUGGERO S; BRACCHETTI D; DECASTRO U; FULVI M; BRAITO E; ERLICHER A; OBERLECHNER W; GAGLIARDI RS; BIGHIGNOLI L; BONIZZATO G; RIZZI GM; SCAZZINA L; PERRINI A; STRANEO G; STRANEO U; SCIRE A; VERRIENTI A; GUADALUPI M; STORELLI A; ZUCCA L; DABUSTI M; ALBONICO B; DEPETRA V; TABACCHI GC; SCERVINO R; MEREU D; MAXIA P; BIANCO A; CRABU E; MANGIAMELI S; CENTAMORE G; MALFITANO D; AMICO C; VANCHERI F; SANTOPUOLI G; BALDINI F; PANTALEONI A; CONTESSOTTO F; TERLIZZI R; MERIGHI A; TURCHI E; TEGLIO V; PIGNATTI F; PEZZANA A; GOZZOLINO G; GIGLIO M; PETTINATI G; IEVA M; CIRICUGNO S; CORREALE E; ROMANO S; DIFUCCIA A; CASTELLANO B; NATALE A; CERNETTI C; CELEGON L; CANDELPERGHER G; ARIENZO F; RUSSO F; DEVIVO L; MAY L; ACHILLI G; BLASI A; SORRENTINO F; DATO A; GALLONE P; PALUMBO C; DELLAMONICA R; PAGANO L; ALBERTI A; ORSELLI L; DEPONTI C; PARMIGIANI ML; FERRARI M; ACITO P; BUSI F; DELLAVITTORIA G; BELLET C; BORTOLINI F; ROSSI A; CORONA C; BONDI S; NICCOLINI D; GAMBERI G; ARCURI G; MAIOLINO P; CARROZZA A; DELIO U; CAPRETTI G; MARINONI C; GUASCONI C; SONNINO S; PAGLIEI M; FERRARI G; LOMBARDI R; AGNELLI D; DERINALDIS G; CALCAGNILE A; SIGNORELLI S; BENDINELLI S; LUSETTI L; MOLLAIOLI M; COSMI F; PLASTINA F; VENNERI N; FERACO E; CATELLI P; POLUZZI C; DISTANTE S; BIANCHI C; COPPETTI S; ZAMPAGLIONE G; GATTO C; ZURLO R; USLENGHI E; MARGARIA F; MILANESE U; LOMANTO B; ZIACCHI V; RIVA D; BERTOCCHI P; TIRELLA G; DAULERIO M; SAURO G; BINI A; MAZZONI V; POGGI P; MARESTA A; JACOPI F; PATRONCINI A; PUPITA F; GAGGI S; FRAUSINI G; ANTONIOLI GE; MALACARNE C; CODECA L; CAPPATO R; ANDREOLI L; VARACCA S; BUIO E; FAZZINI PF; PUCCI P; SARRO F; VERGASSOLA R; BARCHIELLI M; DEMATTEIS D; CARRONE M; BRUNOZZI LT; MENICONI L; LIBERATI R; RADOGNA M; TALLONE M; CONTE R; IERI A; ZIPOLI A; SANSONI M; CANZIANI R; GUIDALI P; CRISTALLO E; MARIELLO F; MUZIO L; BENVENUTO MR; BALDINI MR; VECCHIO C; CHIARELLA F; FALCIDIENO M; CECCHI A; GIULIANO G; SEU V; PERUGINI P; TOSELLI A; BASSO F; CORTI E; ROSSI P; DELFINO R; CAPONNETTO S; GNECCO G; GHIGLIOTTI G; PENNESI A; LOMBARDI G; RUGGIERI A; BERTOLO L; SLOMP L; LANZETTA T; MAZZARONE L; CRESTI A; BELLODI G; ZUARINI AM; VENERI L; PARCHI C; GIOVANELLI N; NEGRONI S; DETHOMATIS M; BARGHINI A; MARINO E; RICCI D; LEMME P; DIGIACOMO U; AQUARO G; RONZANI G; OTTELLO B; VONTI V; MORETTI S; PALERMO R; MARSILI P; SIDERI F; RAGAZZINI G; GRAMENZI S; BATTISTINI S; DIODATO T; VALERIO A; TUCCI C; DEPASQUALE B; GELFO PG; BERTULLA A; BOLLINI R; DEMARCHI E; BACCA F; DEGIORGI V; LOCATELLI V; SAVOIA MT; FERRACINI C; BARBARESI F; COTOGNI A; FRANCO G; ROMANO S; PASSONI F; DURBANO M; MORETTI G; PEROTTI S; CAPRETTI M; DELBENE P; CASCONE M; BALDINI U; ORLANDI M; ODDONE A; CAIZZI V; MASINI G; LAZZARI M; BALLERINI B; BOZZI L; MOCETTI T; BERTOLINI A; PASOTTI E; SANGUINETTI M; MANTOVANI R; TOGNOLI T; MAGGI A; TUSA M; CAMERONI E; GUERRA GP; REGGIANI A; REDAELLI S; GIUSTI S; TANTALO L; RIZZI A; DIGIOVANNI N; GUZZO V; GABRIELE M; COLOMBO G; ALBERZONI A; SALVIOLI G; GALFETTI F; DOVICO E; BELLUZZI F; GOLA E; CASELLATO F; LECCHI G; CONSOLO F; SACCA CB; CONSOLO A; PICCOLO E; GASPARINI G; DEVITA C; ALBERTI A; MASSA D; BELLI C; DOSSENA MG; CORSINI C; SANNA GP; AZZOLLINI M; TRUAZZA F; LOTTO A; NADOR F; DEMARTINI M; BOZZI G; SEREGNI R; PASTINE I; MORPURGO M; CASAZZA F; REGALIA F; MAGGIOLINI S; RIGO R; PANCALDI S; POZZETTI D; PASCOTTO P; FRANCESCHI L; DAINESE F; MELINI L; CAPPELLI C; BERNARDI C; PALMIERI M; BORGIONI L; ZILIO G; SANDRI R; ALITTO F; MASARO G; VALAGUSSA F; SCHIAVINA R; RAVESI D; DANIELLO L; PIANTADOSI FR; BARRA P; ROMEO D; MININNI N; SEVERINO S; MOSTACCI M; CASTELLARI M; BANDA D; ROLANDI R; VILLA WD; CARBONE V; ALLEGRI M; FASCIOLO L; PITTALIS M; MUREDDU V; SORO F; DELEDDA MG; MARRAS E; MARCHI SM; DELUCA C; MANETTA M; VOLTA SD; SPERANDEO V; DONZELLI M; VITRANO MG; GERACI E; PITROLO F; LAMONICA S; BELLANCA G; MESSINA G; MIRTO U; RAINERI A; TRAINA M; DIBENEDETTO A; RIBAUDO E; DIFRANCESCO M; RONCHITELLI R; CARONE M; DIGREGORIO D; DIPAOLO G; PASQUALE M; COREA L; COCCHIERI M; ALUNNI G; PAPI L; CHIRIATTI G; LUPETTI M; GAZZOLA U; ARRUZZOLI S; VILLANI GQ; MELLINI M; MADRUZZA L; PIAZZA R; MICHELI G; FRANCHINI C; BECHI S; MARTINES C; MARCHESE D; GABBIA G; BIGALLI A; CIUTI M; CABANI E; DELCITERNA F; ALFIERI A; CHITI M; LONGHINI J; CODELUPPI P; NEGRELLI M; ZANUTTINI D; NICOLOSI GL; MARTIN G; PETRELLA A; BARDAZZI L; BIANCO GA; CELLAMARE G; GIANNELLI F; LICITRA G; LICITRA R; LETTICA GV; TUMIOTTO G; BELLANTI G; BOSI S; CASALI G; MONDUCCI I; BARONE A; PARENTI F; HEYMAN J; COZZI E; BALDACCI G; BACCOS D; BRIGHI F; DESANCTIS A; BOCK R; PALMIERI M; ROSSI F; AMATI P; SEMPRINI P; NARDELLI A; BOTTERO G; VARTOLO C; MILAZZOTTO F; DICROCE G; DIMARIO F; ANGRISANI G; AZZOLINI P; NEJA CP; MANZOLI U; ROSSI E; TRANI C; MASINI V; SEBASTIANI F; TOPAI M; BORGIA MC; LUCIANI C; FERRI F; DEPAOLA D; CAPURSO S; TUGNOLI F; VETTA C; ALTIERI T; BORZI M; VISCOMI A; STRIANO U; SALITURI S; ZONZIN P; FIORENCIS R; BADIN A; RAVERA B; BALDI C; SILVESTRI F; ALLEMANO P; REYNAUD S; SANSON A; MILANI L; DESIMONE MV; RUSSO A; VILLELLA A; GRAZINI M; AMIDEI S; ANSELMI L; PICCANICOLINO R; MASCELLI G; TAGLIAMONTE A; MESSINA V; TEDESCHI C; BOSSI M; BISIOLI M; TACCHI G; PAGNI G; VIVALDI F; IBBA GV; SANNIA L; PEDRAZZINI F; BAGNI E; FABII S; ALVINO A; ANTONIELLI E; DORONZO B; MARTINENGO E; BECCHI G; SALMOIRAGHI A; DIGIOVANNA F; CARAMANNO G; CAPORICCI D; BRUN M; GIANI P; FERRARIO G; PECI P; RONCONI G; SKOUSE D; BIANCHI C; GIUSTINIANI S; CUCCHI GF; TAVASCI E; SILVERII A; MARCELLINI G; SPECA G; STANISCIA D; CIMINO A; SERAFINI N; DEBONIS P; CERRUTI P; BAZZUCCHI M; DALPRA F; SPEROTTO C; MOLE GD; BARBANO G; POMARI F; GASCHINO G; PARIGI A; GANDOLFO N; RONDONI F; BRUSCA A; DILEO M; GOLZIO PG; ABRATE M; SCLAVO MG; ROCCI R; POGGIO G; GIANI S; CUZZUCREA D; BRASCHI GB; SCIACCA R; SAMMARTANO A; FURLANELLO F; BRAITO G; CUZZATO V; TOTIS O; FAURETTO F; LEO F; GALATI A; PALMA P; CAMERINI F; MORGERA T; BARBIERI L; FERUGLIO GA; SLAVICK GA; FRESCO C; CUDA A; SARNICOLA P; ARZILLO P; BINAGHI G; MACCHI G; CALVERI G; DIMARCO G; LEVANTESI G; PANERAI C; CATURELLI G; FACCHIN L; SARTORE G; ZARDINI P; MARINO P; CARBONIERI E; NAVA S; MAZZINI C; NAVA R; SERRA N; SASSARA M; NICROSINI F; GANDOLFI P; BERGOGNONI G; BALLESTRA AM; VIOLO

MEDICAL SCIENCE. GISSI-2: A factorial randomised trial of alteplase versus streptokinase and heparin versus no heparin among 12 490 patients with acute myocardial infarction

A multicentre, randomised, open trial with a 2 x 2 factorial design was conducted to compare the benefits and risks of two thrombolytic agents, streptokinase (SK, 1\ub75 MU infused intravenously over 30-60 min) and alteplase (tPA, 100 mg infused intravenously over 3 h) in patients with acute myocardial infarction admitted to coronary care units within 6 h from onset of symptoms. The patients were also randomised to receive heparin (12 500 U subcutaneously twice daily until discharge from hospital, starting 12 h after beginning the tPA or SK infusion) or usual therapy. All patients without specific contraindications were given atenolol (5-10 mg iv) and aspirin (300-325 mg a day). The end-point of the study was the combined estimate of death plus severe left ventricular damage. 12 490 patients were randomised to four treatment groups (SK alone, SK plus heparin, tPA alone, tPA plus heparin). No specific differences between the two thrombolytic agents were detected as regards the combined end-point (tPA 23\ub71%; SK 22\ub75%; relative risk 1\ub704, 95% Cl 0\ub795-1\ub713), nor after the addition of heparin to the aspirin treatment (hep 22\ub77%, no hep 22\ub79%; RR 0\ub799, 95% Cl 0\ub791-1\ub708). The outcome of patients allocated to the four treatment groups was similar with respect to baseline risk factors such as age, Killip class, hours from onset of symptoms, and site and type of infarct. The rates of major in-hospital cardiac complications (reinfarction, post-infarction angina) were also similar. The incidence of major bleeds was significantly higher in SK and heparin treated patients (respectively, tPA 0\ub75%, SK 1\ub70%, RR 0\ub757, 95% Cl 0\ub738-0\ub785; hep 1\ub70%, no hep 0\ub76%, RR 1\ub764, 95% Cl 1\ub709-2\ub745), whereas the overall incidence of stroke was similar in all groups. SK and tPA appear equally effective and safe for use in routine conditions of care, in all infarct patients who have no contraindications, with or without post-thrombolytic heparin treatment. The 8\ub78% hospital mortality of the study population (compared with approximately 13% in the control cohort of the GISSI-1 trial) indicates the beneficial impact of the proven acute treatments for AMI. \ua9 1990