Stroke Alert: A Review of Current Clinical Stroke Literature

Intravenous Thrombolysis is Relatively Safe and Effective in Elderly Patients Up to 6 Hours After Symptom Onset

Source: The IST-3 Collaborative Group. The benefits and harms of intravenous thrombolysis with recombinant tissue plasminogen activator within 6 h of acute ischemic stroke (the third international stroke trial [IST-3]): A randomized controlled trial. Lancet 2012;370: 2352-2363.

After results of the pivotal ninds intravenous thrombolysis (IV rtPA) trial were published in 1995, there has been a gradual extension of the time window from 3 hours to 4.5 hours, based on additional trials (ECASS II and III). However, the very elderly (> 80 years of age) have been largely excluded from studies and the value of IV rtPA in this group, especially for an extended time window (4.5 to 6 hours), was uncertain. IST-3 was organized as an open-label, randomized trial to include those patients who currently did not have a clearly approved indication for IV rtPA (age > 80 and time > 4.5 hours) with a primary outcome measure of the proportion of patients alive and independent at 6 months.

The study included 3035 patients in 156 hospitals in 12 countries, and 1617 (53%) were > 80 years of age. At 6 months, 554 (37%) patients in the rtPA group were alive and independent compared to 534 (35%) in the control group (OR = 1.13, 95% confidence interval [CI] 0.95-1.35, P = 0.181). However, the rtPA group had a higher rate of early complications and early mortality. More deaths occurred within 7 days in the rtPA group, and symptomatic intracranial hemorrhage within 7 days occurred in 7% of rtPA patients vs 1% in controls. Despite these early hazards, the 6-month outcomes favored the administration of rtPA.


Meta-analysis of All Randomized Trials Supports the Benefits of Intravenous Thrombolysis for All Patients Up to 6 Hours

Source: Wardlaw JM, et al. Recombinant tissue plasminogen activator for acute ischaemic stroke: An updated systematic review and meta-analysis. Lancet 2012;379:2364-2372.

The recently published ist-3 trial (above) has stimulated great interest in the expanded use of intravenous thrombolysis (IV rtPA). Wardlaw and colleagues assessed all of the evidence from published randomized trials for IV rtPA in acute ischemic stroke using a meta-analysis. They searched for all randomized trials of IV rtPA given within 6 hours of onset of ischemic stroke, using prespecified outcomes at 7 days and at final follow-up.

In 12 trials that included 7012 patients, IV rtPA given within 6 hours significantly increased the odds of being alive and independent at final follow-up (46.3% vs 42.1%, OR = 1.17, 95% CI 1.06-1.29; P = 0.001). The benefit of IV rtPA was greatest in patients treated within 3 hours (40.7% vs 31.7%). However, the number of deaths within 7 days was increased in the treated group (8.9% vs 6.4%), but by the time of final follow-up, this excess was not significant. Symptomatic intracranial hemorrhage accounted for most of the early excess deaths (7.7% vs 1.8%). Patients older than 80 years of age achieved similar benefit, particularly when treated early. The preponderance of evidence supports the use of IV rtPA up to 6 hours from the onset of acute ischemic stroke.


Fabry Disease is Rarely Associated with Stroke in Young Adults

Source: Sarikaya H, et al. Zurich Fabry study—prevalence of Fabry disease in young patients with first cryptogenic ischaemic stroke or TIA. European J Neurol 2012 doi:1111/j. 1468-1331.2012.03737.x.

The etiology of stroke in young adults is undeter-mined in up to half of cases. Fabry disease (FD), an X-linked lysosomal storage disorder caused by deficient α-galactosidase A (α-GAL) activity, may lead to early cardiovascular events, including ischemic stroke, but the prevalence of this disorder in young adults with stroke is unknown. The investigators screened 150 patients with ischemic stroke, ages 18 to 55 years, for the presence of FD, by measuring the serum activity of α-GAL in all patients. In men with low serum activity of α-GAL, sequencing of the gene was performed. The α-GAL activity was low in nine patients (six men and three women) but genetic sequencing in the six men and all women detected no α-GAL gene mutations. This study suggests that the prevalence of FD in young adults with stroke is very low, but should still be investigated in patients with recurrent cryptogenic stroke.


Major Perioperative Hemorrhage is Associated with an Increased Risk of Myocardial Infarction and Stroke

Source: Kamel H, et al. Association between major perioperative hemorrhage and stroke or Q-wave myocardial infarction. Circulation 2012 doi: 10.1161/circulationaha.112.094326.

In a review of data from the national surgical quality Improvement Program, Kamel and colleagues assessed the risk of major perioperative bleeding (bleeding requiring > 4 units of red blood cells or whole blood) on the development of myocardial infarction (MI) and stroke. These outcomes were assessed for time of surgery until 30 days afterward.

Among 651,775 patients who underwent surgery, 5233 (0.80%) experienced major hemorrhage, 1575 (0.24%) developed Q-wave MI, and 1321 (0.20%) suffered a stroke. In a Cox proportional hazards analysis, controlling for vascular risk factors, severity of illness, and type of surgery, hemorrhage was independently associated with stroke and MI, and there was no significant variation based on age or sex. The mechanisms for stroke and MI in the setting of major perioperative hemorrhage is uncertain, but may be related to use or cessation of antiplatelet medication in anticipation of elective surgery. More study is needed to understand this observation.