American Heart Association

Monthly Archives: August 2015

Initiation of antithrombotic therapy after ICH: Do we do it?

Michelle Christina Johansen, MD

Pennlert J, Asplund K, Carlberg B, Wiklund PG, Wisten A, Åsberg S, and Marie Eriksson M. Antithrombotic Treatment Following Intracerebral Hemorrhage in Patients With and Without Atrial Fibrillation. Stroke. 2015

Pennlert et al. conducted an observational study using the Swedish Stroke Register 2005-2012 with the aim of determining the extent and predictors of initiation of antithrombotic treatment following ICH.

A total of 20,768 patients with a first registered ICH were identified using ICD-10 codes. After excluding for prior ICH diagnosis, death prior to discharge or lack of follow-up 14,045 patients were identified and followed for prescription of antithrombotic therapy. The definition for anticoagulation or antiplatelet therapy was having a dispensed prescription of the medication from a Swedish pharmacy after discharge. Additional demographic data (ICD 10) included hypertension, atrial fibrillation (AF), diabetes and prior ischemic stroke. ICD 10 codes were also used when calculating CHA2DS2-VASc and HAS-BLED scores. Notably congestive heart failure was given points only when the patient had been hospitalized due to a primary diagnosis of heart failure. Due to inability to confirm a labile INR, the HAS-BLED score was modified in consideration of this limitation.

The investigators found that at the time of the ICH, 1454 patients (10.4%) were on anticoagulants, 4018 patients (28.6%) were on antiplatelet drugs, and 132 patients (0.9%) were on both drugs. In the AF population, 1055 patients (43.6%) were dispensed an antiplatelet agent and 258 (11.1%) an anticoagulant by one year after ICH. When comparing this to the population at six months, the numbers were lower with 8.5% on anticoagulants and 36.6% on antiplatelet therapy.

What influenced physicians in prescribing patients with AF anticoagulation? Less severe ICH, younger age, previous anticoagulation, valvular disease, and prior ischemic stroke was significantly associated with anticoagulation. High CHA2DS2-VASc scores did not correlate with anticoagulant treatment but there was an interaction between CHA2DS2-VASc scores and HAS-BLED. When looking at resumption of anticoagulation, patients with concurrent AF were less likely to be restarted on drug than those without AF.

How should the results of this study influence the practicing neurologist? It is clear that there is no consensus when prescribing anticoagulation in patients with AF and that physician tend to shy away from use especially in the first six months. Is this the appropriate response? We know that anticoagulation for AF decreases risk of stroke with CHA2DS2-VASc suggesting 3% risk at 1 year if greater than 1, yet providers appear not to be using this tool to guide decision making. Is this presumed fear of hurting patients warranted? A recent cohort study in Canada did not show an increased mortality or bleeding events after ICH with reinitiating of Warfarin and Majeed et al. in Stroke 2010 suggested that optimal timing for Warfarin after ICH was 10-30 weeks, less than the 6 month data point captured in this trial. While it is important to recognize the limitations of this study (observational, adjusted risk scores etc.), the results should nevertheless refocus the neurologist on the importance of appropriate initiation of anticoagulation in the AF population, even after ICH. Future randomized studies are warranted to enable us to further investigate this complex relationship.

By |August 17th, 2015|treatment|0 Comments

Mechanical thrombectomy for stroke is cost-effective, but scalability remains an issue.

Neal S. Parikh, MD

Ganesalingam J, Pizzo E, Morris S, Sunderland T, Ames D, and Lobotesis K. Cost-Utility Analysis of Mechanical Thrombectomy Using Stent Retrievers in Acute Ischemic Stroke. Stroke. 2015

Five large, randomized clinical trials recently demonstrated that mechanical thrombectomy (MT) significantly reduces disability and mortality in patients presenting with proximal large vessel occlusions. MT is performed after IV-tPA administration or, when IV-tPA is contraindicated, as the sole intervention. In this issue of Stroke, Ganesalingam and colleagues seek to determine whether adjunctive MT for stroke is cost-effective, as compared to IV-tPA alone.


Data from the MT trials were used to determine the proportion of patients expected to achieve three functional categories (independent, dependent and deceased). These data were then run through a long-run Markov state-transition model to estimate the costs and outcomes over 20 years. The Markov model was transformed every 3 months over 20 years, which means patients in the independent (mRS 0,1,2) category were given the ability to have a recurrent stroke and change to any of the three states. The model utilizes cost data from the United Kingdom’s National Health Services (NHS): the cost of TPA was $2,953, the cost of MT was $13,803. The model makes a reasonable, evidence-based assumption that functional outcome correlates with quality adjusted life years (QALYs). Cost effectiveness was determined by assessing the incremental cost per gained QALY and the Net Monetary Benefits (NMB) of adjunctive MT over IV-tPA alone. NHS thresholds for willingness to pay per QALY were utilized: $33,000-$49,500.

The incremental cost of MT over IV-tPA alone was $11,651 per QALY gained. The NMB was below even the lower willingness to pay thresholds. Varying the cost of MT up to $33,000 and the utility of functional independence did not negate the results.

Given the meaningful clinical impact of MT on disability and death and the cost-effectiveness of the therapy, it is imperative that the treatment be made available to more patients. The therapy will become more cost-effective with improvements in stroke referral networks, technology and futile inter-hospital transfer rates (1). However, propagation of MT will face costly infrastructure challenges, as, even under optimal modeling, access to comprehensive stroke centers is limited in the United States (2). It would be worthwhile to assess the comparative and cost effectiveness of directed stroke prevention as compared to stroke treatment infrastructure development.

References:
(1) Fuentes, et al. Futile interhospital transfer for endovascular treatment in acute ischemic stroke. Stroke. 2015;46:2156-2161.
(2) Mullen, et al. Optimization modeling to maximize population access to comprehensive stroke centers. Neurology. 2015;84:1196-1205.

Despite Being Anticoagulated, Permanent Afib Patients are at Higher Risk of Stroke then Non-Permanent Afib Patients

Duy Le, MD

Senoo K, Lip GYH, Lane DA, Büller HR, and Kotecha D. Residual Risk of Stroke and Death in Anticoagulated Patients According to the Type of Atrial Fibrillation: AMADEUS Trial. Stroke. 2015 


There is no question that atrial fibrillation is clearly a risk factor for stroke. Prior studies yield mixed results when it comes to duration of atrial fibrillation and risk of embolism. While the debate rages on, Senno et al attempt to answer this question by performing a post-hoc analysis of the AMADEUS trial. The AMADEUS trial evaluated afib patients treated with fixed dose idraparinux vs. oral VKA therapy. Senno et al take this data set and evaluate the permanent afib vs non-permanent afib group with regards to a primary outcome of cardiovascular death or stroke. They hypothesize that patients with permanent afib along with heart failure are at highest risk of the aforementioned outcome.


2072 patients (46%) had non-permanent AF with 16% having pre-existing heart failure. 2484 patients (54%) had permanent afib, with 29% of those patients having heart failure. With regards to the primary end point: sixty eight patients (3 per 100 patient years) in the permanent afib group and 31 patients (1.7 per 100 patient years) in the non-permanent group exhibited a stroke or cardiac event. Due to a low overall event rate however, there was not enough power to detect a difference between subgroups of those with and without heart failure.


Weaknesses of the study include the inherent fact that this study is a post hoc analysis. Additionally, a low outcome rate makes it difficult to perform a logistic regression analysis to rule out confounding factors affecting the outcome. Nonetheless, it does show a correlation between permanent afib leading to a higher risk of stroke. In the big picture, we should potentially be more wary of patients in permanent afib, as they have been shown here to still have an increased risk of stroke despite being anticoagulated. Although this may suggest that sinus conversion of afib may reduce future stroke in conjunction with anticoagulation, more studies would have to be done to validate such an idea.

By |August 13th, 2015|treatment|0 Comments

The ABC/2 score is an accurate measurement for ICH

Peggy Nguyen, MD

Webb AJS, Ullman NL, Morgan TC, Muschelli J, Kornbluth J, Awad IA, et al. Accuracy of the ABC/2 Score for Intracerebral Hemorrhage: Systematic Review and Analysis of MISTIE, CLEAR-IVH, and CLEAR III. Stroke. 2015

The ABC/2 score is a simple method used by both clinicians and researchers to assess intracranial hemorrhage (ICH) size; however, the score has only been validated in small research cohorts. In this study, Webb et al. perform an analysis and systematic review of the validity of the ABC/2 score in three large clinical trials, MISTIE, CLEAR-IVH, and CLEAR III to address whether the ABC/2 score, in both a specialized reading center (RC) as well as a local research site, is an accurate and valid score for determining ICH volume as well as eligibility and clot resolution in trials for ICH.

In their analysis of 4369 scans, the authors found that, when compared to the reference-standard of CT-based planimetry (CTP), both RC-ABC/2 scores as well as site-ABC/2 scores were valid measures of ICH volume for eligibility and clot resolution in all trials. Specifically, RC-ABC/2 scores had good accuracy in defining ICH volume, and categorizing ICH volume as mild, moderate, or severe. Site-ABC/2 scores were less accurate, but still acceptable. ABC/2 scores tended to be less accurate with lobar hemorrhages, larger ICHs, and irregular or heterogenous clots, a conclusion also supported in part by their systematic review, which, although too heterogenous for quantitative analysis, did identify ten studies, of which 2 found greater errors with larger ICHs, and 2 found greater errors with more irregular ICHs.

This study is the largest validation of the ABC/2 score, providing good evidence that the ABC/2 score, which can be performed easily, is accurate and valid. Keeping in mind its possible limitations in certain types of ICH (lobar, larger and more irregular size), this gives clinicians and researchers greater confidence in using the ABC/2 score both in clinical practice and in research, especially in smaller settings where more accurate CT based measurements may not be quickly feasible.

By |August 12th, 2015|hemorrhage|0 Comments

CHA2DS2VASc score as a predictor of recurrent stroke in non-AF patients.

Jay Shah, MD 

Andersen SD, Gorst-Rasmussen A, Lip GYH, Bach FW, and Bjerregaard Larsen TB. Recurrent Stroke: The Value of the CHA2DS2VASc Score and the Essen Stroke Risk Score in a Nationwide Stroke Cohort. Stroke. 2015  

There is great interest in developing clinical scoring systems that stratify patients based upon ischemic stroke risk profiles. CHA2DS2VASc score is one such system where congestive heart failure, hypertension, age 65-74 years, diabetes, peripheral artery disease, and female gender earn a point while history of stroke or TIA and age >75 register 2 points. This score has been validated in patients with atrial fibrillation (AF) and is utilized to determine anticoagulation candidacy. It has also been shown to predict recurrent stroke in non-AF population but has not been adequately replicated. In this observational cohort study, the authors assessed the ability of CHA2DS2VASc score to predict recurrent stroke, death, and cardiovascular event using registry-based data of adults without AF and first-time stroke across a 10-year span. Essen Stroke Risk Score, a risk score specifically developed for the stroke population, was also calculated as a comparison. It allocates one point for age 65-75 years (2 for >75), hypertension, diabetes, myocardial infarction, other cardiovascular disease, peripheral arterial disease, smoking and previous stroke or TIA.

The cohort consisted of 42,182 patients. Patients were followed-up for an average of 3.5 years. Mean CHA2DS2VASc score was 4.3 and mean Essen Stroke Risk Score was 2.4. Increasing values of both scoring systems were associated with an increased risk of all three outcomes. One and five-year hazard ratios for CHA2DS2VASc score of > 7 were 1.56 and 1.90, respectively. Essen Stroke Risk Score had marginally better discriminatory performance in relation to stroke recurrence.

The difference in stroke recurrence rates between the lowest and highest risk scores were fairly modest, as reflected in the low hazard ratios (hazard ratio of 1.2 in CHA2DS2VASc score of 4 versus 1.56 in CHA2DS2VASc score of > 7). This implies that incremental addition of stroke risk factors only minimally increased stroke risk and prior ischemic infarct results in much higher baseline risk outweighing the impact of other risk factors. Overall, the CHA2DS2VASc score did correlate with increased risk of stroke, death, and cardiovascular events but further refinement is needed and clinical application and decision making based upon the score in this population may be premature. An area of further interest would be to determine mechanism of stroke recurrence and evaluate if there is correlation with clinical scoring systems. Finding such an association would help guide tailored therapy thereby decreasing stroke risk.

By |August 11th, 2015|prognosis|0 Comments

Does it matter how long you’ve had diabetes?

Ali Saad, MD

Overvad TF, Skjøth F, Lip GYH, Lane DA, Albertsen IE, Rasmussen LH, and Larsen TB. Duration of Diabetes Mellitus and Risk of Thromboembolism and Bleeding in Atrial Fibrillation: Nationwide Cohort Study. Stroke. 2015

The authors questioned the current CHA2DS2-VASc guidelines of treating all patient with afib + diabetes with an anticoagulant to prevent stroke. Using the nationwide Danish registry they followed about 130,000 patients with a diagnosis of nonvalvular afib between 2000 and 2011 for 4 years. 12.4% of these patients also had diabetes. primary outcome was thromboembolic events. They found that the longer a person had diabetes, the higher their risk of thromboembolism was: 

  • 0-4 years conveyed a risk of HR 1.11 (1.03-1.2) 
  • 15 or more years conveyed a risk of 1.48 (1.29-1.7)

On further analysis they found that the relationship was dose dependant. Duration had no effect on bleeding risk while on anticoagulation, which challenges the idea of prior stroke + diabetes as a relative exclusion criteria for IV tPA in the 4.5 hour window per the ECASS III paper. It makes sense that the longer you have a atherogenic disease such as diabetes, the more likely you are to develop thromboembolic disease. Diabetes may serve as marker of other (or the currently established) mechanisms underlying afib.

Limitations of this study include:
– when they controlled for baseline use of an antiplatelet agent, used death as an outcome measure, included patients with a diagnosis of cancer, or controlled for CHA2DS2-VASc components, there was no difference in primary outcome between short and long duration of diabetes
– when limiting the analysis to patients treated with a vitamin K antagonist, there was no difference in primary outcome
– retrospective nature
– it’s unclear how long these patients actually had diabetes, they may have just been newly diagnosed when admitted for another reason. regardless, there still appears to be a dose dependant relationship between duration of diabetes and thromboembolic risk.
– the study excluded patients with thromboembolism/TIA on the day of admission and those who died
– study is limited to the use of vitamin K antagonists and not the DAOCs
– bleeding related to a vitamin K antagonist was only captured in those who had their vitamin K antagonist started within 30 days of afib diagnosis
– it’s difficult to control for comorbidities as they would increase in prevalence as the duration of diabetes increases

How does this study change my practice?
Like any other component of metabolic syndrome, I’ll counsel patients that the longer they’ve had the disease, the more damaged their heart and vasculature are as a result. I don’t think we can conclude that diabetes independently conveys additional risk as the association disappeared with controlling for various things as mentioned above. as the authors note, the duration of diabetes likely correlates with how sick one’s cardiovascular system is due to the various associated comorbidities. I don’t currently use diabetes + prior stroke as an exclusion criteria for the 4.5 hour window for tpa.

Neuromuscular Electrical Stimulation for Post-Stroke Spasticity

Rizwan Kalani, MD  

Stein C, Fritsch CG, Robinson C, Sbruzzi G, and Méa Plentz RD. Effects of Electrical Stimulation in Spastic Muscles After Stroke: Systematic Review and Meta-Analysis of Randomized Controlled Trials. Stroke. 2015

Spasticity occurs in 20-30% of individuals with prior stroke. Common management strategies include administration of GABAergic agents (baclofen), ankle-foot orthotics, physical therapy, and tendon surgeries. Given inconsistent results from prior randomized controlled trials (RCTs), Stein et al did a systematic review and meta-analysis of studies evaluating the effect of neuromuscular electrical stimulation (NMES) on post-stroke spasticity.

The authors reviewed the literature for RCTs that assessed the effect of NMES (with or without additional therapeutic intervention) for spasticity after stroke. Studies evaluating at least three days of NMES, regardless of dosage, and applied to the upper or lower extremities, were included. Two independent reviewers selected the studies, extracted relevant data, and assessed for risk of bias. The primary outcome was spasticity (per the modified ashworth scale) and secondary outcome was range of motion (ROM) (by goniometer).

Of the 29 RCTs (with 940 subjects) that met the inclusion criteria for the systematic review, 14 were included in the meta-analysis (the other 15 had missing data and used other scales to assess spasticity). Most studies used NMES frequencies of 18-50 Hz and pulse duration from 0.1-0.3 seconds. NMES (alone or combined with other treatment) was associated with reduction in spasticity (-0.30, 95% CI: -0.58 – -0.03) compared to the control group. The 12 studies that combined NMES with another therapeutic modality for spasticity significantly reduced spasticity (-0.35, 95% CI: -0.63 – -0.07) whereas the two studies that evaluated NMES alone did not. Interestingly, reports that used NMES on the legs showed a significant reduction in spasticity (-0.78, 95% CI: -1.02 – -0.54) but those with NMES applied to the upper extremity did not. NMES (alone or with other intervention) was associated with an increase in ROM (2.87, 95% CI: 1.18-4.56). Again, when NMES was combined another modality, a significant increase in ROM was noted (2.73, 95% CI: 1.07-4.39); this did not hold true when NMES was used alone. Application to the leg and elbow improved ROM, whereas use on the wrist did not.

NMES combined with other therapeutic interventions improves spasticity and increases ROM after stroke. RCTs evaluated varied in the time the intervention was started after stroke, treatment duration, stimulation parameters used, degree of spasticity and functional deficit, as well as comparative treatments evaluated in certain studies; these factors may affect response to NMES. Establishing efficacy would be best assessed by a large, high-quality RCT. However, based on this analysis, it is worth considering this option in conjunction with a physiatrist and the patient.