References for thrombolysis lecture by Dr. Rob Stafford, January 2015

Papers

Brown SGA, Macdonald SPJ, Hankey GJ. Do risks outweigh benefits in thrombolysis for stroke? BMJ. 2013 Aug 29;347(aug29 1):f5215–5.

Lenzer J. Why we can’t trust clinical guidelines. BMJ (Clinical research ed). 2013 Jun 14;346(jun14 2):f3830–0.

Prasad V, Vandross A, Toomey C, Cheung M, Rho J, Quinn S, et al. A Decade of Reversal: An Analysis of 146 Contradicted Medical Practices. Mayo Clinic Proceedings. Elsevier; 2013 Aug;88(8):790–8. [Full Text]

Shinton R. Questions about authorisation of alteplase for ischaemic stroke. The Lancet. Elsevier Ltd; 2014 Aug 23;384(9944):659–60.

Mann J. Efficacy of Tissue Plasminogen Activator (Tpa) for Stroke: Truths about the NINDS study: setting the record straight. Western Journal of Medicine. 2002;176(3):192. [Full Text]

Godlee, F. How guidelines can fail us. BMJ 2014;349:g5448

Marler, J.R. Early stroke treatment associated with better outcome. Neurology 2000 55;11:1649-1655

Wardraw, J. Thrombolysis for acute ischaemic stroke. Cochrane Database Syst Rev. 2014 Jul 29;7:CD000213. doi: 10.1002/14651858.CD000213.pub3.

Selected FOAMed

Thrombolytics for acute ischaemic stroke, thennt.com

 SGEM#85: Won’t get fooled again (tPA for CVA) Thesgem.com

SGEM#70: The secret of NINDS thesgem.com

SGEM#29: Stroke me, stroke me thesegem.com

Stroke thrombolysis  lifeinthefastlane.com 

The major trials of thrombolytic agents in stroke: Clicking on the trial will hyperlink you to the pubmed abstract page.

Trial Journal Time Primary Benefit Harm
MAST – Italy

(n=622)

Lancet 1995 <6hrs None Increased early death
ECASS-1

(n=620)

JAMA 1995 <6hrs None Benefit did not outweigh risk
NINDS-1

(n=291)

NEJM 1995 <3hrs None No difference
NINDS-2

(n=333)

NEJN 1995 <3hrs 13% absolute mRS at 90d Increased ICH
MAST-Eu

(n=310)

NEJM 1996 <6hrs None Stopped due to harm
ASK

(n=340)

JAMA 1996 <4hrs None Stopped due to harm
ECASS-2

(n=800)

Lancet 1998 <6hrs None Increased ICH
ATLANTIS-B

(n=613)

JAMA 1999 3-4hrs None Stopped unlikely benefit, increased ICH
ATLANTIS-A

(n=142)

Stroke 2000 <6hrs None Stopped early due to harm, mortality at 90d 23% vs 7%
ECASS-3

(n=821)

NEJM 2008 3-4.5hrs 7% absolute benefit Increased ICH
DIAS-2

(n=193)

Lancet 2009 3-9hrs None Increased ICH
IST-3

(n=3035)

Lancet 2012 <6hrs None Increased early death