2015 BENEFIT Matteo Casegni.pptx
Transcription
2015 BENEFIT Matteo Casegni.pptx
ScuoladiSpecializzazioneinMala/edell’ApparatoCardiovascolare Dire8oreProf.MassimoVolpe FacoltàdiMedicinaePsicologia,UniversitàdiRomaSapienza AnnoAccademico2014-2015 Dr.Ma8eoCasenghi Proge8oFormazioneAvanzatainCardiologianelWeb2015 ScuoladiSpecializzazioneinMala/edell’ApparatoCardiovascolare Dire8ore:Prof.MassimoVolpe E-mail:massimo.volpe@uniroma1.it Coordinatore:Dr.GiulianoTocci E-mail:giuliano.tocci@uniroma1.it Original Article Randomized Trial of Benznidazole for Chronic Chagas’ Cardiomyopathy Carlos A. Morillo, M.D., Jose Antonio Marin-Neto, M.D., Ph.D., Alvaro Avezum, M.D., Ph.D., Sergio Sosa-Estani, M.D., Ph.D., M.P.H., Anis Rassi, Jr., M.D., Ph.D., Fernando Rosas, M.D., Erick Villena, M.D., Roberto Quiroz, M.D., Rina Bonilla, M.D., Constança Britto, Ph.D., Felipe Guhl, M.Sc., Elsa Velazquez, Ph.D., Laura Bonilla, M.Sc., Brandi Meeks, M.Eng., Purnima Rao-Melacini, M.Sc., Janice Pogue, Ph.D., Antonio Mattos, M.Sc., Janis Lazdins, M.D., Ph.D., Anis Rassi, M.D., Stuart J. Connolly, M.D., Salim Yusuf, M.D., Ph.D., for the BENEFIT Investigators N Engl J Med Volume 373(14):1295-1306 October 1, 2015 BernC.NEnglJMed2015;373:456-466 Phases of Trypanosoma cruzi Infection Acute Phase 6-8 weeks Chronic Phase Indeterminate Form 70-80% Determinate Form 20-30% Chagas’ CMP GI Chagas’ Study Overview InclusionCriteria: • PaZents aged between 18 and 75 years with two posiZve serological tests for CHAGAS disease and any one or more of the following: – – – – Abnormalelectrocardiogram IncreasedcardiothoracicraZo Complexventriculararrhythmiason24-hECGmonitoring Evidence of regional wall moZon abnormality or reduced (<50%) global LV systolicfuncZonorincreasedLVend-diastolicdiameteron2DEcho ExclusionCriteria: • • • • • • • • • NewYorkHeartAssociaZonclassIVordecompensatedheartfailure EvidenceofothereZologyofdilatedcardiomyopathy Previoustreatmentwithtrypanocidalagents Inabilitytocomplywithfollow-up HistoryofseverealcoholabuseorotherdrugaddicZon KnownchronicrenalfailureorhepaZcinsufficiency Pregnancyorbreastfeeding Megaesophaguswithsevereswallowingimpairment Otherdiseasessignificantlycurtailinglifeexpectancy Pa3entFlow: Time0 EnnrolledandRandomized N=2854 AllocatedtoBenzonidazole(BNZ) N=1431 AllocatedtoPlacebo N=1423 300mgfor80days Mean FU 5.4 Years IncludedinprimaryITTanalysis N=1431 IncludedinprimaryITTanalysis N=1423 PrimaryOutcome: • Firsteventofanyofthecomponentsofthecomposite outcomeofdeath,resuscitatedcardiacarrest,sustained ventriculartachycardia,inserZonofapacemakeror implantablecardioverter–defibrillator,cardiac transplantaZon,newheartfailure,strokeorother thromboembolicevent SecondaryOutcome: • ResponsetotreatmentonthebasisofresultsonPCR assay BaselineCharacteris3cs Benzonidazole N=1431 Placebo N=1423 MeanAge-yrs 55.4±10.7 55.2±11.2 MaleSex-no.(%) 726(50.7) 682(47.9) AnyECGabnormaliZes–no(%) 1335(93.3) 1348(94.7) NYHAclassI–no.(%) 1065(74.4) 1045(73.5) MeanLVEF-% 54.4±14.8 54.6±14.6 WallMoZonAbnormality–no.(%) 431(38.3) 422(37.6) DiureZcs–no.(%) 435(30.4) 425(29.9) ACE-IorARBs–no.(%) 710(49.6) 700(49.2) Beta-blockers–no.(%) 444(31.0) 431(30.3) Amiodarone–no.(%) 284(19.8) 267(18.8) PrimaryCompositeOutcomeduring7YearsofFollow-up PrimaryOutcomeandItsComponents,Hospitaliza3ons,andDeaths PrimaryOutcome,AccordingtoSubgroup ConversiontoNega3veResultsonPCR,AccordingtoSubgroup Conclusions • TrypanocidaltherapywithbenznidazoleinpaZentswith established Chagas’ cardiomyopathy significantly reduced serum parasite detecZon, but did not significantlyreducecardiacclinicalprogression. Conclusions WHYTHISTRIALISNEUTRAL? • Wrongunderlyingpathogenicconcept? • Wrongdrugregimen? • WrongpopulaZon? ScuoladiSpecializzazioneinMala/edell’ApparatoCardiovascolare Dire8oreProf.MassimoVolpe FacoltàdiMedicinaePsicologia,UniversitàdiRomaSapienza AnnoAccademico2014-2015 Dr.Ma8eoCasenghi GrazieperlaVostraA8enzione! Proge8oFormazioneAvanzatainCardiologianelWeb2015 ScuoladiSpecializzazioneinMala/edell’ApparatoCardiovascolare Dire8ore:Prof.MassimoVolpe E-mail:massimo.volpe@uniroma1.it Coordinatore:Dr.GiulianoTocci E-mail:giuliano.tocci@uniroma1.it