American Heart Association

Monthly Archives: February 2016

Stereotactic radiosurgery leads to good outcomes in patients with unruptured AVMs

Peggy Nguyen, MD

Ding D, Starke RM, Kano H, Mathieu D, Huang P, Kondziolka D, et al. Radiosurgery for Cerebral Arteriovenous Malformations in A Randomized Trial of Unruptured Brain Arteriovenous Malformations (ARUBA)-Eligible Patients: A Multicenter Study. Stroke. 2016

Since the publication of the ARUBA trial1 suggesting higher rates of neurologic morbidity and mortality with interventional therapy versus medical therapy for unruptured AVMs, conservative management with monitoring and symptom alleviation alone has gained acceptance. However, the study has been criticized in the interim for its short follow-up period of 33 months, the heterogeneity of interventional therapy used, and the excessive hemorrhage rates in the intervention group. Taking into account these limitations, it is not clear whether certain types of interventions may be beneficial over other types, nor is it clear whether long-term prognosis was adequately measured.

The authors address some of these gaps by performing a retrospective, multicenter cohort analysis of ARUBA-eligible patients who received treatment with radiosurgery and define predictors of AVM radiosurgery outcomes in ARUBA-eligible patients. 509 patients were included from a total of seven institutions and underwent radiosurgical treatment with successful AVM obliteration in 75% of the study subjects. A combined post-radiosurgery morbidity and mortality rate of 8.8% was demonstrated. 23 (4.5%) suffered permanent neurologic morbidity and 22 patients (4.3%) died, albeit no deaths were associated directly with the radiosurgery procedure. 69.5% of subjects achieved a favorable outcome. Variables independently associated with favorable outcomes were a smaller AVM maximum diameter and non-eloquent AVM location.

The authors appropriately point out that the primary treatment goal in the management of AVMs is the elimination of hemorrhage risk. This study provides compelling data on the safety of radiosurgery, which is minimally invasive and addresses some of the critiques of ARUBA, including a longer follow up period of up to 10 years. However, what the study does not do (and is not designed to do) is to more definitively address whether radiosurgery would have better outcomes compared to medical treatment. This would need to be addressed in further prospective randomized trials.

1. Mohr, et al. Lancet 2014 (393): 614-621

By |February 4th, 2016|treatment|0 Comments

Argatroban may be safe but not effective in acute atherothrombotic stroke

Jay Shah, MD

Wada T, Yasunaga H, Horiguchi H, Matsubara T, Fushimi K, Nakajima S, and Naoki Yahagi N. Outcomes of Argatroban Treatment in Patients With Atherothrombotic Stroke: Observational Nationwide Study in Japan. Stroke. 2016   

Three randomized trials have suggested that argatroban is effective and safe for early therapy in acute ischemic stroke. However, these trials were small and a meta-analysis concluded early anticoagulants were not beneficial.

There has been some suggestion that argatroban may play a role in neuroprotection possibly due to its thrombin inhibition effects. This retrospective observational study investigated argatroban safety and efficacy in patients with acute ischemic strokes using a Japanese database that includes various parameters such as demographics, diagnosis, drugs used, and outcomes. In Japan, argatroban is recommended in patients with atherothromotic stroke within 48 hours from symptom onset. Argatroban is infused continuously at dose of 60mg daily for first 48 hours followed by twice daily 10mg infusions for the next 5 days. Inclusion criteria included atherothromotic stroke, admission within 1 day of stroke and antiplatelet agents during hospitalization. Patients who received thrombolysis or underwent endovascular intervention were excluded. Patients were then divided into 2 groups: those who received argatroban on admission and those who did not. Outcomes were 7-day mortality, hemorrhagic complications and modified rankin score (mRS) on discharge. In total, 2289 pairs of patients were included. In this population, there were no significant differences in the primary outcomes. Therefore, there was no added benefit of argatroban on outcomes.  

A strength of this study is the use of propensity score matching in order to compensate for lack of blinding. However, bias is still possible in that important parameters may not have been captured within demographics and other clinical parameters. Rationale for clinical decision making (i.e. whether to treat with argatroban) is not directly available but inferred from other parameters. Other limitations include the exclusion of patients receiving thrombolytics, which could potentially increase hemorrhage risk and omission of National Institutes of Health Stroke Scale which serves as a barometer of stroke severity. Lastly, given the retrospective nature of the study, the nature of the atherosclerotic disease could not be graded. It may be of interest if outcome differences exist between mild to moderate carotid stenosis (<70%) versus severe stenosis (>70%).

By |February 3rd, 2016|treatment|1 Comment

Low ankle-brachial index and stroke recurrence, vascular death

Citing a need for improved recurrent stroke risk prediction, the authors of this systematic review and meta-analysis explore the association between low ankle-brachial index (ABI) and recurrent stroke risk.

The meta-analysis included only prospective trials that collected at least 12 months of follow-up data regarding recurrent stroke, vascular events and/or vascular death. In pooling the data, their primary endpoints were recurrent stroke and combined vascular events (recurrent vascular event and vascular death). Ischemic stroke and TIA were variably included as outcomes. 

Ultimately, 11 studies with 5,374 participants were included in the meta-analysis. Pooled analysis of relative risks of recurrent stroke and combined vascular endpoint in patients with low ABI were 1.55 (95% CI, 1.28-1.88) and 1.91 (95% CI, 1.65-2.22), respectively.

There was heterogeneity among the studies in terms of covariates entered into individual multivariate models; this limits precise estimation of the association between ABI and recurrent stroke risk. Publication bias was also present, which also limits our ability to draw confident conclusions.

The authors conclude that there is a robust association between low ABI and recurrent stroke and vascular outcome risk.

The bottom line
Even if ABI indeed predicts recurrent stroke independent of traditional vascular risk factors, existing data do not allow us to conclude that ABI measurement provides recurrent stroke predictive value in excess of that provided by advanced standard-of-care stroke diagnostics. Ideal recurrent stroke risk prediction models will incorporate data collected for standard stroke evaluation and will therefore be parsimonious and cost-effective.
By |February 2nd, 2016|prevention|0 Comments

High Blood Sugar Leads to Not-So-Sweet Outcomes in Mechanical Thrombectomy Patients

Ilana Spokoyny, MD

Kim JT, Jahan R, Saver JL, and for the SWIFT Investigators. Impact of Glucose on Outcomes in Patients Treated With Mechanical Thrombectomy: A Post Hoc Analysis of the Solitaire Flow Restoration With the Intention for Thrombectomy Study. Stroke. 2016

The medical management of patients post-stroke is critical to improving their functional outcomes. Stroke patients treated in dedicated stroke units have been shown to have better outcomes than those treated in general medical wards. Aside from blood pressure optimization, preventing infection, and avoiding fevers, glucose management has been a focus in predicting functional outcomes following stroke. Hyperglycemia predicts poor outcomes after ischemic strokes but while it is intuitive to think that tighter glucose control improves outcomes, a recent Cochrane review did not show benefit of maintaining normoglycemia. The authors hypothesized that reperfusion status should be taken into account, so chose to conduct an analysis on patients who underwent mechanical thrombectomy. 

This study evaluated outcomes of 143 stroke patients treated with mechanical thrombectomy in the SWIFT trial (Solitaire vs. Merci) to determine if presenting with hyperglycemia (glucose > 140 mg/dl) was associated with worse outcomes, and how the degree of reperfusion played into this relationship. Only half of the cohort also received IV tPA.

Hyperglycemia at presentation was associated with worse functional outcome at 90 days. The hyperglycemic patients were more likely to be disabled, and less likely to have an excellent functional outcome (mRS 0-1) at 3 months. Overall, for every 10mg/dl increase in presenting glucose level, a patient was 13% less likely to have an excellent outcome (mRS 0-1 at 90 days). This approached significance (p=0.054). No effects of hyperglycemia were seen on intracranial bleeding or death.

The presenting glucose level did not affect the rate of complete reperfusion. Previous studies of IV tPA showed reduced rates of recanalization in hyperglycemic patients. This result suggests that using mechanical thrombectomy overcomes these barriers. 

Among patients with complete reperfusion, there was a trend toward worse outcomes in those presenting with hyperglycemia, but this was not statistically significant. However, among patients with incomplete reperfusion, higher presenting glucose levels were associated with worse 90 day outcomes. In fact, for every 10mg/dl increase in the glucose, a patient (with incomplete reperfusion) was 42% less likely to achieve excellent outcome. This is consistent with previous studies showing larger infarct formation in hyperglycemic non-recanalized pateints.

A previous randomized trial showed that there was no benefit to tight glucose management post stroke. However, that trial did not take into account reperfusion status, and based on the results of this study, further research is warranted to determine whether tight glucose control improves outcomes specifically in those patients with incomplete reperfusion, as they may be more prone to the deleterious effects of hyperglycemia.

By |February 1st, 2016|treatment|0 Comments