Late Breaking Science from the American Stroke Association’s International Stroke Conference
San Diego 2014
Report for BASP trainees committee
We can describe stroke research in 2013 by paraphrasing Frank Sinattra - it was a very good year (for practice changing research results). Based on the original science presented at the International
Stroke Conference, San-Diego; 2014 also promises to be a vintage year for stroke research.
In the first of the large clinical trial sessions, Angel Chamorro from Barcelona presented data from the URICO-ICTUS study. This trial randomised patients receiving conventional thrombolysis for ischaemic stroke to additional uric acid infusion or placebo. Across 411 patients, the trialists did not show a significant improvement on the pre-specified primary outcome, although benefit of uric acid was shown using alternative analyses and across secondary outcomes. Here I must confess a conflict of interest. In Glasgow we are due to commence a multicentre trial of uric acid lowering as a secondary prevention strategy. The paradox of an intervention that may confer a beneficial effect on acute events but increases risk of poor outcome with chronic exposure is not uncommon in cardiovascular medicine and Professor Chamorro’s results should not dissuade stroke physicians from randomising patients to our study!
At last year’s ISC promising results from Canada described the efficacy of an external cardiac monitoring device for detection of occult atrial fibrillation (AF). This year’s CRYSTAL-AF study looked at the utility of an implantable cardiac monitoring device. In a cohort of 441 patients with a robust label of cryptogenic stroke (all participants had as a minimum, vascular imaging and transoesophageal echocardiography) at six months the implanted devices detected occult AF in 8.9% versus 1.4% for standard care. At 36 months follow up the differences were more impressive, 30% occult AF detection for implantable devices versus 3% for standard care. The trialists argue that implantable device should now be standard of care. This strategy would have major resource implications and may not be suitable for all patients, however the message from these studies looking at AF detection seems to be that a single 24 hour “tape” is not sufficient.
Many stroke clinicians and researchers view vascular cognitive impairment as “the new frontier” in research. Frank C Barone from New York discussed data from his laboratory’s work on vascular cognitive impairment. His team created a mouse model with concomitant vascular risk factors of hypertension and carotid stenosis. The mice develop an early cognitive impairment/executive dysfunction state that is said to be similar to human vascular cognitive impairment. The mice also exhibited an inflammatory, pro-thrombotic phenotype and the New York group used this as the basis for an intervention. When the animals were randomised to the oral direct thrombin inhibitor
Dabigatran, results were impressive. Compared to placebo, the Dabigatran arm showed a substantial reduction in cognitive impairment markers. Promising results from animal stroke models are often lost in translation to “real world” human beings. However, if thrombin inhibition can make even a modest impact on vascular cognitive decline then this could be a game-changing study.
However, the cognitive substudy of SPS3 reminds us that preventing cognitive decline in humans is still a challenge. SPS3 presented primary results last year, showing no effect of dual antiplatelet and

possible mortality benefit of intensive blood pressure reduction in patients with subcortical stroke.
In the substudy presented this year, patients were assessed with a neuropsychological battery and cognitive change was described. Neither blood pressure lowering nor dual antiplatelet impacted on cognitive decline but perhaps more surprising was the general slow rate of cognitive change.
Although called the “International” Stoke Conference, the ISC often has a North American focus. So it is always nice when a UK researcher presents important and scientifically robust data. This was certainly the case with Lisa Manning from Leicester who presented a new analysis of the data from the INTERACT2 study. INTERACT 2 had suggested that early, aggressive blood pressure (BP) lowering in intracerebral haemorrhage (ICH) may reduce death and disability. In the new analysis, rather than absolute BP, the effect of BP variability was described with a focus on the first seven days. Results suggested that BP variability was independently associated with poor outcome. These data make BP management in ICH even more of a challenge. The ideal would be to lower BP acutely and then keep BP at this low level for the first days, but we all know how difficult this can be in practice. We may soon be able to offer further evidence based intervention in ICH. The CLEAR-III trialists presented safety data on the first 250 patients enrolled in this RCT of external ventricular drain and intraventricular thrombolytic for patients with intraventricular haemorrhage. Safety data are reassuring and we await the final results of the trial.
Any stroke conference worth its salt will have a study looking at neuroprotection. The FASTmag study, led by Jeffrey Saver, looked at magnesium sulphate as a potential neuroprotectant. The study was neutral in keeping with previous magnesium in stroke trials. More exciting was the design and execution of the FASTmag trial. The investigative compound was delivered hyper-acutely by paramedic teams with median time from stroke onset to treatment of an impressive 40 minutes.
The study was neatly summarised in the session’s post results discussion as “right study, right method, wrong molecule”. If this very early intervention paradigm can be applied to other treatments we will likely see many more positive studies at future stroke conferences.
While 2013 was a good year for stroke research, it was more of an “annus horribilis” for acute neurovascular intervention, with several high profile neutral studies. The ICARO-3 data do not help the case for neurovascular procedures. These case-control data compared standard intravenous thrombolysis with intra-arterial thrombolysis in 648 patients with extracranial carotid occlusion.
There was no difference in death and disability comparing intravenous and intra-arterial approaches delivered up to six hours post event. These data are not from a randomised controlled trial and so all the caveats of observational comparisons apply; nonetheless at present intra-arterial therapy cannot be recommended in patients with carotid occlusion who are eligible for standard thrombolysis. There will be a potentially lively debate on the role of neurovascular intervention in stroke as part of the BASP trainees meeting in Glasgow. We have a few places still available at the meeting, which will be held on 7-8 th March – hopefully see you there.
Terry Quinn
BASP Scientific and Trainees Committees
Terry.quinn@glasgow.ac.uk