David H. Newman|Ashley Shreves
Thrombolysis in acute ischaemic stroke
Icahn School of Medicine at Mount Sinai|Icahn School of Medicine at Mount Sinai
ist31the ist3 collaborative groupthe benefits harms intravenous thrombolysis recombinant tissue plasminogen activator within 6 h acute ischaemic stroke third international stroke trial ist3 randomised controlled triallancet 2012 379 23522363summary full text full text pdf pubmed scopus 972 google scholar largest arguably important study thrombolytic drugs acute stroke reports thrombolytic administration within 6 h symptom onset compared standard treatment openlabel randomised trial patients could participate unless felt thrombolytics promising treatment stroke despite established advantage designs confer treatment groups2hrbjartsson boutron blinding randomized clinical trials imposed impartialityclin pharmacol ther 2011 90 732736crossref scopus 55 google scholar trial unable show statistical difference death dependence primary outcome unadjusted p04 adjusted p018 ist3 collaborative group concludes however ist3 shows efficacy thrombolytics basis secondary exploratory analysis3sandercock p lindley r wardlaw j et alfor ist3 collaborative groupupdate third international stroke trial ist3 thrombolysis acute ischaemic stroke baseline features 3035 patients recruitedtrials 2011 12 252260crossref pubmed scopus 37 google scholar age improving literacy appraisal interpretation evidence troubling see study definitive failure primary outcome described success secondary endpoints used basis conclusions concerning 4 increase mortality noted 7 days p00003 despite longer apparent 6 months clinically important increase early deaths suggests substantial loss lifedays patients thrombolytic group followup period proper conclusion based findings ist3 benefit detected perhaps importantly increase early deaths advantageous study design raise concerns important aggregate harm thrombolytic treatment might masked declare conflicts interest thrombolysis acute ischaemic stroke authors replydaniel fatovich colleagues brendon smith david newman ashley shreves interpret third international stroke trial ist3 rigidly stating nonsignificant result statistically inefficient dichotomous analysis primary outcome measure implies thrombolysis 6 h ineffective since trial sought provide information risks benefits people meet licence criteria thrombolysis posed subtle question thrombolysis work fulltext pdf