tPA for stroke debate at IAEM 2014

25 Oct

The 2014 meeting of IAEM was a great experience. For a country of 4.5 million with just over 70 emergency physicians we put on a pretty good show I think. I like to use “we” even though I had no part to play in organising the damn thing. Credit to David Menzies for leading the work.

There was almost a mini SMACC reunion with Rick Body, Mark Wilson, Weingart and John Hinds all in attendance and speaking. Through the premiere of Code Black I also managed to have dinner with Billy Mallon which was everything you would expect it to be.

I also got the chance to do my first stroke thrombolysis debate. I got into all this about 3 or 4 years ago when I first started listening to the abstracts and heard Jerry Hoffman on it. It was the first real topic to get me really excited about critical appraisal and reading the medical literature. If it turns out us skeptics are all wrong on tPA then at least I’ve gained a few skills along the way.

Below is my half of the debate. The pro side was delivered by a local stroke physician and I have to confess that I lost the debate. I must be doing something wrong if the emergency doc can lose a debate on stroke thrombolysis to a room of other emergency docs…

As with most short debates like this, it isn’t a deep and considered view of all the evidence, it’s as much about making the argument as anything else. Any feedback is of course welcomed. I’ve tried to include a reasonably comprehensive list of references at the bottom.

It’s probably worth noting that I work in a hospital that has a very enthusiastic stroke thrombolysis team (which as part of my job I have a small role in activating) and to give credit where it’s due they provide a great service with the quickest and best assessment in the ED you can imagine. It’s very rare in Ireland to get a consultant to the patient’s bedside within minutes of arrival but our stroke team does this well. We would do well to provide close to such a service for our trauma patients but that’s another story altogether…

 

References:

The BMJ Pro Con Debate

The Ioannidis Paper

  • Ioannidis JPA. Why Most Published Research Findings Are False. PLoS Med. Public Library of Science; 2005;2(8):e124. [full text]

A decade of reversal

  • 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]

The Lenzer paper on the problems with guidelines

Roger Shinton’s letter to the Lancet

Simon Thompson’s paper on heterogeneity in meta-analysis [H/T Dave Newman for this one]

  • Thompson SG. Why sources of heterogeneity in meta-analysis should be investigated. BMJ (Clinical research ed). 1994 Nov 19;309(6965):1351–5. [Full Text]

The systematic review mentioned

  • Wardlaw JM, Murray V, Berge E, del Zoppo G, Sandercock P, Lindley RL, et al. Recombinant tissue plasminogen activator for acute ischaemic stroke: an updated systematic review and meta-analysis. Lancet. 2012 Jun 23;379(9834):2364–72. [Full Text]

Jeff Mann’s break down of the NINDS patients revealing the baseline imbalance

  • 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]

The RCTs

  • Intravenous desmoteplase in patients with acute ischaemic stroke selected by MRI perfusion-diffusion weighted imaging or perfusion CT (DIAS-2): a prospective, randomised, double-blind, placebo-controlled study. Lancet Neurology 2009 Feb.;8(2):141–150. PMCID 2730486
  • Effects of alteplase beyond 3 h after stroke in the Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET): a placebo-controlled randomised trial. Lancet Neurology 2008 Apr.;7(4):299–309.PMID 18296121
  • Randomised controlled trial of streptokinase, aspirin, and combination of both in treatment of acute ischaemic stroke. Multicentre Acute Stroke Trial–Italy (MAST-I) Group. The Lancet 1995 Dec.;346(8989):1509 -1514. PMID: 7491044 
  • Thrombolytic therapy with streptokinase in acute ischemic stroke. The Multicenter Acute Stroke Trial–Europe Study Group (MAST-E). N Engl J Med 1996 Jul.;335(3):145–150. PMID: 8657211
  • Streptokinase for acute ischemic stroke with relationship to time of administration: Australian Streptokinase (ASK) Trial Study Group. JAMA 1996 Sep.;276(12):961–966. PMID: 8805730
  • Recombinant tissue-type plasminogen activator (Alteplase) for ischemic stroke 3 to 5 hours after symptom onset. The ATLANTIS (B) Study: a randomized controlled trial. Alteplase Thrombolysis for Acute Noninterventional Therapy in Ischemic Stroke. JAMA 1999 Dec.;282(21):2019–2026. PMID: 10591384 
  • The rtPA (alteplase) 0- to 6-hour acute stroke trial, part A (A0276g) : results of a double-blind, placebo-controlled, multicenter study. Thromblytic therapy in acute ischemic stroke study investigators.(ATLANTIS A) Stroke 2000 Apr.;31(4):811–816.  PMID 10753980
  • Tissue plasminogen activator for acute ischemic stroke. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group (NINDS). N Engl J Med 1995 Dec.;333(24):1581–1587. PMID: 7477192
  • Intravenous thrombolysis with recombinant tissue plasminogen activator for acute hemispheric stroke. The European Cooperative Acute Stroke Study (ECASS). JAMA 1995 Oct.;274(13):1017–1025.1. PMID: 7563451 
  • Randomised double-blind placebo-controlled trial of thrombolytic therapy with intravenous alteplase in acute ischaemic stroke (ECASS II). Second European-Australasian Acute Stroke Study Investigators. The Lancet 1998 Oct.;352(9136):1245–1251. PMID: 9788453 
  • Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke (ECASS III). N Engl J Med 2008 Sep.;359(13):1317–1329. PMID: 18815396 
  • The IST-3 collaborative group. The benefits and harms of intravenous thrombolysis with recombinant tissue plasminogen activator within 6 h of acute ischaemic stroke (the third international stroke trial [IST-3]): a randomised controlled trial. Lancet. 2012 May 23.PMID: 22632908

 

A few #FOAMed resources

Leave a Reply

Your email address will not be published. Required fields are marked *