Friday April 18, 2014
When I was a resident, we normally started someone on aspirin if they weren't on it when they had a stroke. If they were, we might consider switching to a different drug, such as clopidogrel. We almost never used the two together, as the thought was that this would increase the risk of bleeding without reducing the chance of someone getting stroke in the future.
Then came the recent CHANCE Trial. This large trial involved 5170 people with transient ischemic attacks (TIA) or small strokes, who were given either aspirin or both aspirin and clopidogrel. The outcome was better in the group treated with both drugs together.
Interestingly, despite being a well-designed trial, results have not been replicated outside of China. For example, a recently published trial in Neurology found no such benefit to combined therapy with aspirin and clopidogrel after small strokes.
Perhaps there is something unique about the population that was studied--can the results be generalized to people elsewhere? A subsequent trial, the POINT trial, is currently underway to clarify that question.
Wang Y, Johnston SC, Wang Y. Clopidogrel with aspirin in minor stroke or transient ischemic attack. N Engl J Med. 2013 Oct 3;369(14):1376-7. doi: 10.1056/NEJMc1309713.
Sunday April 13, 2014
I've already touched on one negative trial in stroke--on to another. While using catheters to do endovascular thrombus retrieval or lysis in acute stroke can effectively open up the vessel, several trials have not shown any benefit overall to patient outcome. This holds true even if neuroimaging techniques are being used to try to triage people to endovascular treatment. The severity of the stroke doesn't seem to matter. Whether someone uses a MERCI device, Penumbra device, Solitaire, or intraarterial tissue plasminogen activator (tPA), there seems to be no benefit over the current standard of giving IV tPA alone.
So when will be abandon all hope for catheter-based stroke treatment? Not yet. Some of these treatments are very time dependent--for example, 90 minutes is the cutoff to do a catheterization for the heart after a heart attack. Maybe we're just getting people to the catheter too late to be useful? Endovascular therapy vs. best medical therapy in people triaged by image selection is still also an open question, being evaluated in the SWIFT PRIME and DAWN trials.
In the meantime, though, there doesn't seem to be much use to catheterization that we've found in acute stroke. While the question is certainly still worth exploring, it would be probably be ill-advised, for example, to transfer from one hospital to another just so someone could get a catheter treatment for an acute stroke.
Friday April 11, 2014
"Time is brain." Such is the stroke neurologist's mantra, reflecting the loss of millions of neurons every minute part of the brain goes without blood trapped behind a clot. The strongest medication to help people with stroke, tissue plasminogen activator (tPA), can only be given within a few hours of the first symptoms, and the sooner the better. The FDA still only approves use of the medication within 3 hours, though research suggests that there may be benefits in some people out to 4.5 hours.
One of the contributors to the time delay between symptoms and tPA is the need to obtain a CT scan first to ensure that the patient's symptoms are not in fact due to a bleed. The same clot busting drug that can be so useful in ischemic stroke would be disasterous in the setting of an intracerebral hemorrhage. But a CT takes precious time, as does waiting for a neurological evaluation.
The city of Berlin is pioneering a novel approach to this dilemma. STEMO involves an ambulance equipped with a neurologist, a CT scanner, and a technician. A hemorrhage can thereby ruled out and an appropriate examination done before the patient ever reaches the hospital. People are much more likely to be sooner with this technique--in fact, the time from the first phone call to being given tPA is only 58 minutes. That's better than many hospitals have once the patient enters their doors.
The results are impressive. 25% more patients are discharged home with this treatment than without the in-ambulance evaluation. I wonder what it would take to establish something like this in the States?
Thursday April 3, 2014
Hot on the heels of my post about "negative" trials not getting enough press, here's something about a very well designed, impressive trial. The goal of the FAST-MAG trial was to see if magnesium could improve neurological outcomes following stroke if given relatively quickly after the person first noticed symptoms.
Dr. Jeffrey Saver in Los Angeles arranged a double-blind, placebo controlled trial of IV magnesium given even before the patient reached the hospital. This took 8 years, and involved over 1700 participants, as well as over 95 study coordinators and research associates. This was a huge and laudable effort.
At three months, magnesium has no beneficial effect on recovery from stroke. We won't give magnesium--that's one thing that has been learned. But this study also had a very high number of patients treated within two hours of stroke--using similar methods with agents known to work, such as tPA, could have major implications for stroke victims.
JL Saver, S Starkman, M Eckstein, S Stratton, F Pratt et al. Methodology of the Field Administration of Stroke Therapy - Magnesium (FAST-MAG) phase 3 trial: Part 1 - rationale and general methods. International Journal of Stroke. Volume 9, Issue 2, pages 215-219, February 2014