American Heart Association

Monthly Archives: October 2017

Low-Dose Rivaroxaban Plus Aspirin: A New Way to Prevent Strokes?

Philip Chang, MD

Eikelboom JW, Connolly SJ, Bosch J, Dagenais GR, Hart RG, Shestakovska O, et al. Rivaroxaban with or without Aspirin in Stable Cardiovascular Disease. N Engl J Med. 2017

This landmark trial published in the New England Journal of Medicine found that in 27,395 patients with stable atherosclerotic cardiovascular disease (ASCVD), aspirin 100 daily plus rivaroxaban 2.5mg twice daily was superior to aspirin alone and rivaroxaban alone in preventing the primary outcome of cardiovascular death, stroke, or heart attack. In addition, secondary outcomes of all-cause death were also significantly lower in the aspirin-plus-rivaroxaban group. The effect size was large enough for the study to stop prematurely for superiority of the aspirin-plus-rivaroxaban group. From this, it is clear that treatment with rivaroxaban plus aspirin is superior to aspirin alone in a patient with coronary or peripheral vascular disease in preventing ischemic stroke (p=<0.001) without significantly increased adverse effects. However, this brings into the question – what about patients who already have a history of ischemic stroke? Ischemic stroke is an ASCVD risk equivalent, and this study brings into question – do we need to start adding apixaban for secondary ischemic stroke prevention for all-comers?

By |October 30th, 2017|clinical|0 Comments

World Stroke Day: Sunday, October 29

Nerses Sanossian, MD, and José G. Merino, MD
Blogging Stroke Editors

World Stroke Day is an opportunity to focus on how to reduce the global burden of the deadliest and most morbid brain disease. Stroke is a global disease that exerts a particularly high burden on developing nations, where it is the second leading cause of death. Stroke remains a leading cause of death and disability throughout the United States and Europe despite many recent advances in stroke care. However, World Stroke Day also allows us an opportunity to recognize breakthroughs in stroke care and review priorities for the future.

Advances in acute stroke have created major disparities in care nationwide and worldwide. The four most impactful stroke treatments of the past 30 years — stroke units, intravenous thrombolysis, emergency/prehospital systems, and endovascular therapy — are currently available to the minority of people around the word. Most countries are just starting to develop stroke units. Intravenous thrombolysis is unavailable or beyond the financial means for most people in the world. Emergency systems of care are non-existent in most countries. Many countries do not have a single neuroendovascular practitioner. In a world where basic medical care is limited, how can advances in stroke care be translated into meaningful results?

Serum Gamma-Glutamyl Transferase at Time of Stroke is Associated With Post-Stroke Mortality and Recurrent, Fatal Stroke

Neal S. Parikh, MD 

Tu W, Liu Q, Cao J, Zhao S, Zeng X, Deng A. γ-Glutamyl Transferase as a Risk Factor for All-Cause or Cardiovascular Disease Mortality Among 5912 Ischemic Stroke. Stroke. 2017

In light of an increasing interest in and understanding of the association between liver disease and cerebrovascular disease, Wen-Jun Tu and colleagues sought to explore the association between serum γ-glutamyl transferase (GGT) and post-stroke mortality.

In their well-designed and well-powered prospective, multicenter cohort observational study, the authors enrolled 5,912 patients within 24 hours of acute ischemic stroke. The study was conducted in China. They excluded patients with known hepatobiliary disease and alcohol abuse. Serum GGT level at baseline was the exposure of interest, and patients were followed for a median of 1 year with regular telephone interviews and review of death certificates. The primary outcome was all-cause mortality, and cardiovascular death (including fatal stroke) was separately adjudicated. Men and women were analyzed differently because normative values for GGT are sex-specific.

Omega-3 Fatty Acid Biomarkers: A Potential Marker of Incident Ischemic Stroke Risk?

Mark R. Etherton, MD, PhD

Saber H, Yakoob MY, Shi P, Longstreth Jr. WT, Lemaitre RN, Siscovick D, et al. Omega-3 Fatty Acids and Incident Ischemic Stroke and Its Atherothrombotic and Cardioembolic Subtypes in 3 US Cohorts. Stroke. 2017

In this entry, I discuss a recent publication by Hamidreza Saber and colleagues regarding the relationship of circulating omega-3 fatty acids levels and incident ischemic stroke.

The authors set out to clarify the impact of omega-3 fatty acids on ischemic stroke incidence. Observational studies of self-reported omega-3 fatty acid consumption and omega-3 fatty acid supplementation trials have previously produced disparate results. As such, the authors quantified circulating omega-3 fatty acid levels in association with ischemic stroke incidence from 3 separate prospective cohort studies.

The authors used data from the Cardiovascular Health Study (CHS), Nurses’ Health Study (NHS), and Health Professionals Follow-Up Study (HPFS). Each of these three cohort studies represent distinct patient populations, which does influence the overall generalizability of these results. CHS is a prospective cohort study of adults aged 65 years and older. The NHS is a prospective cohort study of female registered nurses 30 to 55 years of age. Lastly, HPFS is a cohort study of U.S. male health professionals 40 to 75 years of age. Most participants in each study were white (88% in CHS, for example). The analysis of NHS and HPFS was based on a nested case-control study of age and vascular-risk factor matched controls. Ischemic stroke was subdivided into atherothrombotic, cardioembolic, or other. At the time of enrollment in the studies, blood samples were collected and stored for later analysis of omega-3 fatty acid levels. Of note, there were some differences in collection and storage of blood samples for fatty acid analysis between the three studies.

Readmission after Subarachnoid Hemorrhage

Pouya Tahsili-Fahadan, MD

Dasenbrock HH, Angriman F, Smith TR, Gormley WB, Frerichs KU, Aziz-Sultan MA, et al. Readmission After Aneurysmal Subarachnoid Hemorrhage: A Nationwide Readmission Database Analysis. Stroke. 2017

Readmission (within a pre-defined period of time from discharge) is frequently measured and reported as a quality measure for care provided by physicians and hospitals. However, it is debatable whether this measure is an appropriate quality metric for various indications and etiologies of the index hospitalization. Dasenbrock et al. investigated this question by analyzing the Nationwide Readmission Database (NRD) for readmission after aneurysmal subarachnoid hemorrhage (SAH).

Data from this longitudinal administrative database within 21 states were extracted for 3806 non-elective adult patients admitted for treatment of aneurysmal subarachnoid or intracerebral hemorrhage and discharged alive in 2013. Mortality during the index hospitalization and readmission were 11% and 1.7%, respectively, and about two thirds of survivors were discharged home. The median cost of the index and readmission hospitalizations were $266,304 and $45,091, respectively, and readmission was associated with increased total costs. Within the next 30 days from discharge, 10.2% of patients were readmitted with 34.4%, 65.6%, and 82.4% of readmissions within 1, 2, and 3 weeks from discharge, respectively. As expected, patients who were readmitted had higher SAH severity scale, higher incidence of cerebral edema, and complications during their index hospitalization, and were more likely to undergo tracheostomy or gastrostomy, and less likely to be discharged home. Treatment modality (clipping versus coiling) was not associated with increased rate of readmission. Independent predictors for readmission, however, were identified as comorbidity score equal or more than 3, higher SAH severity, and discharge destination other than home; the more predictors, the higher chance of readmission. Of note, high-volume institutions had lower risk of readmission and mortality. The most common reasons for readmission included hydrocephalus, other neurological complications, infections, and thromboembolic events. Neurosurgical procedures and surgeries were among the most common operations performed after readmission. Importantly, hydrocephalus during index hospitalization was associated with increased risk of readmission for hydrocephalus.

Is It Possible to Predict the Occurrence of Cerebral Edema After Intravenous Thrombolysis? An Exploratory Analysis From the SITS-ISTR Registry

Aristeidis H. Katsanos, MD, PhD

Thorén M, Azevedo E, Dawson J, Egido JA, Falcou A, Ford GA, et al. Predictors for Cerebral Edema in Acute Ischemic Stroke Treated With Intravenous Thrombolysis. Stroke. 2017

Even though cerebral edema (CED) is one of the most severe complications of acute ischemic stroke (AIS) and the cause of mortality in 5% of all AIS patients, there are scarce data on risk factors predicting the development of CED following AIS — including the subgroup of AIS patients treated with intravenous thrombolysis (IVT).

Thorén and colleagues aimed to determine potential baseline clinical and radiological predictors of CED after IVT by analyzing data from 42,187 AIS patients recorded in the Safe Implementation of Treatments in Stroke International Register (SITS-ISTR) during a 10-year period. After performing an image-based classification on the severity of post-IVT CED, they found that increased baseline stroke severity, high blood glucose, decreased level of consciousness, the presence of hyperdense artery sign and signs of infract on baseline neuroimaging were the most important baseline predictors for early CED. As expected, patients with CED had worse 3-month functional outcomes and increased mortality rates —proportionally to the severity of edema — compared to patients without CED. Moreover, the authors found increased risk of symptomatic intracerebral hemorrhage in patients with severe CED, providing further support to the hypothesis of a blood-brain disruption induced common pathway leading to both cerebral edema and hemorrhage in the acute phase of cerebral ischemia.

Ticagrelor Versus Aspirin — A Closer Look at ESUS in SOCRATES

Kevin S. Attenhofer, MD

Amarenco P, Albers GW, Denison H, Easton JD, Evans SR, Held P, et al. Ticagrelor Versus Aspirin in Acute Embolic Stroke of Undetermined Source. Stroke. 2017

Embolic stroke of undetermined source is a sub-classification of cryptogenic stroke which describes non-lacunar stroke without an identified cardio embolic source or occlusive atherosclerosis. While multiple pathologies may be at the heart of ESUS, it is thought that the undiagnosed embolic phenomenon driving the ischemia could be treated with anticoagulation. Multiple ongoing and recent trials seek to determine the optimal secondary stroke prevention in patients with ESUS by comparing aspirin to various direct oral anticoagulants (RESPECT-ESUS, NAVIGATE-ESUS, ARCADIA, ATTICUS). Considering the possibility that these studies may be neutral or negative, Amarenco et al. examined the use of antiplatelet agents for ESUS. The authors used data from the Acute Stroke or Transient Ischemic Attack Treated with Aspirin or Ticagrelor and Patient Outcomes (SOCRATES) trial to retrospectively compare ticagrelor and aspirin for ESUS. Their hypothesis was that all or some patients with ESUS would show greater benefit from ticagrelor than aspirin.

Importance of Intravenous Thrombolysis for Large Vessel Anterior Circulation Stroke in the Era of Endovascular Therapy

Tapan Mehta, MBBS, MPH

Mistry EA, Mistry AM, Nakawah MO, Chitale RV, James RF, Volpi JJ, et al. Mechanical Thrombectomy Outcomes With and Without Intravenous Thrombolysis in Stroke Patients. Stroke. 2017

Mechanical thrombectomy (MT) has been proven to be superior to intravenous thrombolysis (IVT) in proximal large vessel anterior circulation strokes (LVO); however, the standard of care is still to provide IVT to eligible patients before MT. Rigorous data is lacking, however; the need for IVT in the patients with LVO who are eligible for MT is being questioned.

The article by Mistry et al is an important meta-analysis of 13 studies that explored the differences in clinical outcomes (mortality, morbidity with mRS (Modified Rankin Scale; 0-2 defined as good outcome), symptomatic intracranial hemorrhagic (sICH), and successful recanalization rates for patients receiving MT+IVT versus only MT (MT – IVT)). This meta-analysis included studies from 2006 to 2016. Separate sub-group analyses were performed for randomized clinical trials (RCT) and non-randomized studies each. Sub-group analysis for the RCT group demonstrated higher, but nonsignificant, Odds Ratio (OR) for good functional outcomes (OR, 1.28 [95% confidence interval (CI), 0.93–1.75], P=0.12) and a significantly lower OR for mortality (OR, 0.56 [95% CI, 0.36–0.86], P=0.007) in MT+IVT compared with MT−IVT patients. The sub-group analysis of patients in nonrandomized studies demonstrated a strong trend with quantitatively similar OR of 1.31 (95% CI, 0.99–1.73, p=0.06) for good functional outcomes and OR 0.76 (95% CI, 0.56–1.03, p=0.08) in MT+IVT compared to MT−IVT patients.

Who Are You? Where Are You From? Mr. Clot?

Qing Hao, MD

Sporns PB, Hanning U, Schwindt W, Velasco A, Minnerup J, Zoubi T, et al. Ischemic Stroke: What Does the Histological Composition Tell Us About the Origin of the Thrombus? Stroke. 2017

During the hyperacute phase of stroke, we all get excited when the interventionists show a piece of clot attached to the device, and then we primarily focus on the cause of the clot by performing various workups, although many times the answer is “unknown.” Can we get some clues from the clot itself?

Sporns and colleagues analyzed the histological clot composition with the aim to define characteristics that would further help to determine the cause of stroke. Clots were collected from 187 acute stroke patients with carotid-T or middle cerebral artery occlusion who underwent thrombectomy at a university medical center. In addition to quantification of fibrin, RBC, and WBC, immunohistochemistry for CD3, CD20, and CD68/KiM1P was also performed.

By |October 4th, 2017|clinical|0 Comments

Neurons Over Nephrons Still Holds True

Sami Al Kasab, MD

Brinjikji W, Demchuk AM, Murad MH, Rabinstein AA, McDonald RJ, McDonald JS, et al. Neurons Over Nephrons: Systematic Review and Meta-Analysis of Contrast-Induced Nephropathy in Patients With Acute Stroke. Stroke. 2017

In the era of mechanical thrombectomy, the use of advanced imaging, such as computed tomographic angiography (CTA) and CT perfusion, has become an essential component in the evaluation of patients presenting with acute stroke symptoms. Due to the concern of acute kidney injury (AKI) that might result from the use of iodine contrast, many stroke centers require having a baseline serum creatinine prior to performing the CTA/CTP imaging; this, however, might lead to delay in obtaining the imaging, which could delay time to treatment.

Previous studies have evaluated the risk of AKI in stroke patients undergoing CTA/CTP; however, the risk remains unclear, with no major impact on the current clinical practice.

In this study, Drs. Brinjikji et al perform a systematic review and meta-analysis of the literature to determine whether acute ischemic stroke (AIS) patients receiving CTA/CTP are at higher risk for AKI than those receiving only non-contrast head CT (NCCT). The authors aim to determine the overall rate of AKI among patients with AIS undergoing CTA/CTP, and whether having chronic kidney disease is a risk factor for AKI after receiving CTA/CTP.

By |October 3rd, 2017|clinical|0 Comments