Papers like this are fabulous. I am 100% in agreement with the physiologic premise that timely reperfusion of the ischemic penumbra is beneficial in acute stroke. I am less enthusiastic about using systemic thrombolysis, because it's akin to smashing a teacup with a sledgehammer. But, until PCI-like therapy is available/safe for the brain, it's all we have.
I am really tired of endless papers from the TPA literature with authors falling all over themselves to present fundamentally flawed data as definitive evidence. In this paper, the authors take the non-randomized TPA population from the SITS-ISTR - and compare it to the non-randomized, non-thrombolyzed population from the VISTA registry. Why is this a problem? Because even though the relative differences are large, the absolute differences are small - and we've already see that what makes the largest absolute difference is stroke after-care, and that all stroke centers are not created equal. The authors acknowledge this, but then justify their results by stating that their numbers are similar to prior, retrospective, non-randomized comparisons performed on subsets of registry data. It's a self-fulfilling prophecy.
They conclude with "Hence, we find no justification to exclude patients from receiving alteplase for acute ischemic stroke if they have a [prior stroke] and also have [diabetes mellitus]" - which is true, unless it bothers you that the mRS 6 (dead) group nearly doubles when TPA is given to the stroke/diabetes groups. Imagine what the reaction to ECASS III would be if TPA wasn't 52% good outcome vs 6.7% death - and was one of these 29% good outcome vs. 23% death, or 25% good outcome vs. 28% death comparisons from the registry data (totally different baseline severity vs. ECASS III, just throwing the numbers out there for hyperbole).
...and, the obligatory:
"Dr. Mishra reports no disclosures. Dr. Ahmed is an employee of SITS International, which received a grant from Boehringer Ingelheim for the SITS-MOST/SITS-ISTR study with alteplase. Dr. Davalos has received speaker or consultancy honoraria from AstraZeneca, Boehringer Ingelheim, Lundbeck Inc., ev3, Ferrer, and Talecris Biotherapeutics. Dr. Iversen has served on scientific advisory boards for Boehringer Ingelheim and Allergan, Inc.; and has received research support from the Danish National Advanced Science Foundation. Dr. Melo reports no disclosures. Dr. Soinne serves on speakers’ bureaus for and has received speaker honoraria from Boehringer Ingelheim, Pfizer Inc, and Siemens; and has served as a consultant for Boehringer Ingelheim. Dr. Wahlgren serves as Chairman of the SITS Scientific Committee; has served on scientific advisory boards for Boehringer Ingelheim and ThromboGenics NV; has received funding for travel and speaker honoraria from Boehringer Ingelheim, Lundbeck Inc., and Ferrer; and serves on the editorial boards of Stroke and Cerebrovascular Diseases. Dr. Lees serves on scientific advisory boards for Boehringer Ingelheim, Talecris Biotherapeutics, Lundbeck Inc., Ferrer, and PhotoThera; and has received speaker honoraria from Boehringer Ingelheim, Lundbeck Inc., ThromboGenics NV, and Talecris Biotherapeutics."
I want to use TPA to treat stroke without reservations, but the literature is broken. Still hoping IST-3 will help define a low-risk population that benefits.
"Thrombolysis outcomes in acute ischemic stroke patients with prior stroke and diabetes mellitus"