A Stroke of Genius: Gains Seen on Many Fronts at Meeting

The American Stroke Association’s 2015 International Stroke Conference held Feb. 11-13 in Nashville, Tenn., likely lifted many spirits with findings that supported new therapies and identified opportunities to improve patient care.

Just add water? Hydration may turn tide in stroke care

Could something as simple as water create a sea change in stroke care? A study unveiled Feb. 12 pointed to dehydration as a factor in poor stroke outcomes, making rehydration a possible pathway for improvement.  

The study used BUN/creatinine ratio and urine specific gravity data to gauge dehydration and diffusion-weighted MR imaging to measure lesion volume 168 patients admitted at a stroke center. For short-term outcomes, 44 percent of the dehydrated patient group had no changes or worse National Institutes of Health Stroke Scale scores compared with 17 percent of the hydrated patient group. By day four, the dehydrated group had a four times increased odds of an unchanged or worse clinical condition.

“I think early hydration is the key,” says presenter Mona Bahouth, MD, a neurologist at Johns Hopkins Hospital in Baltimore. They are continuing to look at the data for longer-term outcomes and if those results hold up they plan to evaluate interventions through a prospective trial. “If it proves positive that rehydrating a patient is helpful to them, then it would be a really cheap and universally available intervention for patients.”

Vitamin D may predict stroke severity

In a retrospective analysis of stroke patients with recorded vitamin D levels, researchers found a nearly fourfold larger stroke risk by two weeks following an event in patients with low vitamin D levels. Low vitamin D also doubled the size of lacunar and nonlacunar strokes.

Insufficient vitamin D levels also appeared to influence the distribution of outcomes, with more than two-thirds of patients with low vitamin D levels showing poorer functional status at three months.

Using infarct size, the team was better able to quantify outcomes related directly to the initial stroke and define initial stroke severity without including outcomes that may be unrelated, such as later death by heart failure.

The next step is to look for validation in a larger group of patients, says presenter Nils Henninger, MD, of the University of Massachusetts Medical School in Worcester. “We find a target population of patients who are at a high risk for stroke and supplement those with vitamin D when the targets are below a certain cut point. Can we modify that risk? … While there are a lot of studies that show that the risk may be higher when vitamin D level is low, there are no studies as yet that show that you can reverse this effect by supplementing vitamin D.”

Insertable monitorcost-effective in cryptogenic stroke patients

Using an insertable cardiac monitor to identify atrial fibrillation in patients with cryptogenic stroke is cost-effective, at least from a UK healthcare system’s perspective.

“The management of cryptogenic stroke patients is currently very difficult and often they don’t get anticoagulated until they have had a second stroke,” says Klaus Witte, MD, a cardiologist at the Leeds Teaching Hospitals National Health Service Trust in the UK and one of the study’s investigators. “The standard of care is aspirin, which we know is effectively pointless in a lot of cases, particularly if there is arrhythmia.”

Their analysis used data from the CRYSTAL AF (Cryptogenic Stroke and Underlying AF) trial, which randomized 441 patients with cryptogenic stroke or transient ischemic attack to either long-term electrocardiographic monitoring with an insertable cardiac monitor (REVEAL XT, Medtronic) or conventional follow-up.

At six months, atrial fibrillation was detected in 8.9 percent of the device group vs. 1.4 percent in the standard-care group. At 12 months, the detection of atrial fibrillation was seven time higher in the insertable cardiac monitor group compared with the control, and it continued to climb up to three years.

The cost-effectiveness model assumed that all patients with detected atrial fibrillation received anticoagulation of either a novel oral anticoagulant (NOAC) or warfarin. For risks, they included cerebrovascular events and treatment-related adverse events.

Patients treated with NOACs tallied an incremental cost-effectiveness ratio (ICER) of $28,308 (£17,184) and those receiving warfarin had an ICER of $21,903 (£13,296). Both anticoagulation approaches fell within the accepted range of value in the UK and the U.S., and also skimmed in below a lower threshold.

Functional outcomes improved by rapid endo treatment

For some patients with acute ischemic stroke, rapid endovascular treatment may offer improved outcomes, according to findings from the ESCAPE trial.

The trial enrolled 316 patients with good collateral circulation, occluded proximal artery in the anterior circulation and small infarct core. They were randomized to receive standard care or standard care plus rapid endovascular treatment with thrombectomy devices, including retrieval stents and balloon guide catheter. ESCAPE was terminated early due to efficacy.

Odds of patients improving by one point on a modified Rankin scale were 2.6 in favor of the intervention. The intervention group also saw 53 percent of patients with a modified Rankin score of two or less at 90 days compared to 29.3 percent of control patients. Fewer patients died at 90 days in the intervention group (10.4 percent) as opposed to the control group (19 percent).

Symptomatic intracerebral hemorrhage rates were higher among patients in the intervention as opposed to those receiving standard care (3.6 percent vs. 2.7 percent, respectively). Measures investigating quality of life and function in patients significantly favored the intervention group.

Stent thrombectomy pulls ahead of alteplase alone

In more proof that time is brain, a randomized trial found that promptly performing thrombectomy with a stent retriever in carefully selected ischemic stroke patients led to better outcomes than did alteplase treatment alone.

The EXTEND-IA (Extending the Time for Thrombolysis in Emergency Neurological Deficits — Intra-Arterial) study evaluated the use of a strategy that combined advanced imaging, current technology and early treatment in patients with ischemic stroke. To be eligible, patients needed to receive intravenous alteplase within 4.5 hours of stroke onset; have anterior circulation ischemic stroke, as detected by CT angiography; have a major artery occlusion; and salvageable brain tissue as seen on CT perfusion imaging.

All patients received alteplase initially and then were randomized to endovascular therapy with the Solitaire Flow Restoration retrievable stent (Covidien) or continued alteplase therapy. The researchers terminated the trial early at 70 patients because of efficacy. 

Mean reperfusion at 24 hours totaled 100 percent with endovascular therapy vs. 37 percent with alteplase alone. Early neurological improvement at three days occurred in 80 percent of the endovascular therapy group vs. 37 percent of the alteplase group. The endovascular therapy group also had improved functional outcomes and were more likely to be independent at 90 days compared with the alteplase group.

TNK tPA as alternative to alteplase appears safe, feasible

Even a minor stroke can lead to disability if paired with an intracranial occlusion. Researchers explored the use of tenecteplase (TNK) tissue plasminogen activator (tPA) to safely treat this type of stroke before it progressed.

TNK is a mutant tPA with a longer half-life and higher fibrin specificity. Reports suggest TNK may be easier to administer and may have lower risks for intracranial bleeding.

The TEMPO-1 (TNK–Tissue-Type Plasminogen Activator Evaluation for Minor Ischemic Stroke With Proven Occlusion) study enrolled 50 patients presenting with minor ischemic stroke and occlusions verified by CT angiography. Patients were then randomized between a 0.1 or 0.25 mg per kg dose of TNK, called tier one and tier two, respectively.

No serious drug-related adverse events were reported for patients given the lower dose. One patient in the higher dose group had a small, transient, symptomatic intracranial hemorrhage. At 90 days, however, the patient had an independent outcome (modified Rankin Score of 2). A total of 90 percent of patients had independent outcomes at 90 days; 66 percent had excellent functional outcomes (modified Rankin score of 0-1).

Among tier one patients, 39 percent had complete recanalization and 17 percent had partial recanalization. Complete recanalization was more frequent among tier two patients (52 percent) and fewer had partial recanalization (9 percent). Complete recanalization led to significantly more patients with excellent functional outcomes at 90 days