American Heart Association


Therapeutic Management of Aspirin Failure – Does Changing the Antiplatelet Regimen Help?

Philip Chang, MD

Lee M, Saver JL, Hong KS, Rao NM, Wu YL, Ovbiagele B. Antiplatelet Regimen for Patients with Breakthrough Strokes While on Aspirin. Stroke. 2017

When your patient has a stroke while on an antiplatelet regimen, a common practice is to switch it. If they were on aspirin, change to clopidogrel. If on clopidogrel, one may think of switching to aspirin plus dipyridamole. While there has been much theory about aspirin failure, or aspirin resistance, there has been scant evidence to suggest that switching antiplatelet agents may benefit patients. Clinicians have switched antiplatelet regimens under the common philosophy, “Insanity is doing the same thing over and over again and expecting different results.” This is with the underlying theory that patients who experience recurrent stroke while on aspirin must have developed aspirin resistance, and blocking another antiplatelet pathway (like ADP) will confer some protective benefit. However, this theory has never been proven or disproven by a clinical study. This article by Lee et al is a great step into this clinical conundrum.

Bridging Therapy for Endovascular Thrombectomy: A Role for Direct Mechanical Thrombectomy?

Mark R. Etherton, MD PhD

Bellwald S, Weber R, Dobrocky T, Nordmeyer H, Jung S, Hadisurya J, et al. Direct Mechanical Intervention Versus Bridging Therapy in Stroke patients Eligible for Intravenous Thrombolysis. Stroke. 2017

In this entry, I discuss the matched pairs analysis of IV tPA eligible patients with large-vessel occlusion (LVO) of the anterior circulation that underwent endovascular thrombectomy (EVT) with or without pre-treatment with IV tPA.

The clinical importance of understanding the role of bridging therapy in patients with LVO is critical for efficaciously triaging this population to stroke centers. The hypothetical scenario is, how should emergency medical services appropriately triage a patient with suspicion for LVO with regards to transfer to a primary stroke center with tPA capabilities or a comprehensive stroke center with EVT capabilities that is further away? This scenario epitomizes why there is great interest in understanding the contribution that bridging therapy with tPA has on outcomes in patients with LVO of the anterior circulation.

The Role of MIST in Recanalization Times for Large Vessel Occlusion

Abbas Kharal, MD, MPH, and Richa Sharma, MD, MPH

Wei D, Oxley TJ, Nistal DA, Mascitelli JR, Wilson N, Stein L, et al. Mobile Interventional Stroke Teams Lead to Faster Treatment Times for Thrombectomy in Large Vessel Occlusion. Stroke. 2017

This retrospective analysis of the expediency of Mobile Interventional Stroke Teams (MIST) in the treatment of acute ischemic stroke (AIS) patients with large vessel occlusions (LVO) introduces an interesting method of delivering acute stroke care in a densely populated urban setting. Contrary to previously adapted AIS treatment models of drip-and-ship (transfer of patients from PSC to CSC) and mothership (transfer directly to CSC while bypassing nearby PSC), the trip-and-treat model introduces the concept of transferring the interventional team — including a neurointerventionalist attending, fellow and radiological technologist — to the PSC where the patient presents. Patients were treated by the trip-and-treat model or the drip-and-ship model based on relative availability of operating rooms and neurosurgical intensive care unit beds at the peripheral hospital and CSC. Interestingly, mean initial door-to-puncture time was shorter in the trip-and-treat model compared to the historic drip-and-ship model {143 mins vs. 222 mins, respectively (P<0.0001)}. Although there was a trend in longer puncture-to-recanalization times for trip-and-treat (P=0.0887), initial door-to-recanalization was still 79 minutes faster for trip-and-treat.

Endovascular Therapy for Stroke Can Be Translated from Ideal World to Real World

Kaustubh Limaye, MD

Mueller-Kronast NH, Zaidat OO, Froehler MT, Jahan R, Aziz-Sultan MA, Klucznik RP, et al. Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke: Primary Results of the STRATIS Registry. Stroke. 2017

It is possible to match “benchmark” workflow timings and clinical outcomes in a community setting for acute stroke patients with large vessel occlusion needing endovascular therapy.

The Systematic Evaluation of Patients Treated with Neurothrombectomy Devices for Acute Ischemic Stroke (STRATIS) registry sought to compare real-world patient workflow and outcome of patients with intracranial large vessel occlusion (LVO) requiring endovascular therapy (EVT). A total of 984 eligible patients with large vessel occlusion were enrolled at 55 different sites with an enrolling cap of 75 patients. Patients with pre-treatment modified Rankin score of 0-1, confirmed LVO, NIHSS≥8 with an intention to be treated with a Medtronic market-released neurothrombectomy device (Solitaire and Mindframe) as an initial device for stent assisted thrombectomy within 8 hours from symptom onset.

Out of 1000 patients enrolled, 16 were deemed to be screen failure resulting in intention to treat analysis of 984 patients. 64% of the patients enrolled received intravenous thrombolysis and mean NIHSS of the enrolled patients was 17. 45.2% of patients were transferred from another facility to the enrolling center. Mean distance from field to the enrolling site was 29 miles with 2/3rd of the patients <25 miles distance from enrolling site. The clinical trials for LVO needing EVT set a few important “benchmarks” for patient workflow: 1) onset to puncture time; 2) door to puncture time (DTP); 3) puncture to reperfusion time (PTR); and 4) the quality of substantial reperfusion (TICI ≥ 2b).

Administration of Statin on Acute Ischemic Stroke Patient (ASSORT) Trial

Aristeidis H. Katsanos, MD, PhD

Yoshimura S, Uchida K, Daimon T, Takashima R, Kimura K, Morimoto T, on behalf of ASSORT Trial Investigator. Randomized Controlled Trial of Early Versus Delayed Statin Therapy in Patients With Acute Ischemic Stroke ASSORT Trial (Administration of Statin on Acute Ischemic Stroke Patient). Stroke. 2017

Even though the role of statins in both primary and secondary stroke prevention has been well established, with a considerable number of acute ischemic stroke (AIS) patients receiving statin treatment during the first days of ictus, the usefulness of statin therapy in the acute phase of cerebral ischemia still remains debatable.

The Administration of Statin on Acute Ischemic Stroke Patient (ASSORT) Trial is a multicenter, Japanese, open-label, randomized clinical trial (RCT) with the aim to determine the efficacy of early (≤24 hours) versus delayed (7th day) statin initiation in AIS. After randomizing a total of 257 patients (early: 131, delayed: 126), authors concluded that there is no superiority of early statin administration for AIS, as no significant differences were found on the 3-month functional outcome, stroke recurrence or mortality between patients receiving early or delayed statin therapy. As highlighted by the authors, the low dose of statins that were administered in the current trial (atorvastatin 20mg/d, pitavastatin 4mg/d or rosuvastatin 5mg/d) could partially account for the aforementioned lack of efficacy, concluding that higher doses should be attested in future studies.

Remote Ischemic Conditioning May Improve Outcomes of Patients With Cerebral Small-Vessel Disease

Alexis N. Simpkins, MD, PhD

Wang Y, Meng R, Song H, Liu G, Hua Y, Cui D, et al. Remote Ischemic Conditioning May Improve Outcomes of Patients With Cerebral Small-Vessel Disease. Stroke. 2017

Cerebral small vessel disease (sCVD) is an important cause of both vascular dementia and lacunar infarction. Accumulation of white matter lesions and lacunar infarcts from sCVD is associated with cognitive dysfunction, increased risk of stroke, and worsened neurologic outcome after stroke. Here the authors test the hypothesis that remote ischemic conditioning (RIC) can improve cognitive outcomes in patients with mild cognitive impairment and cSVD as a follow up to the pilot study in which they showed that cSVD can reduce white matter disease and increase mean velocity of the middle cerebral arteries.

This study was a 1-year, single-center, prospective, double-blinded, randomized, placebo controlled study of consented patients of Han Chinese decent between 45 and 80 years of age with mild cognitive impairment defined by a pre-treatment MMSE and MOCA score, sCVD as defined by the Standards for Reporting Vascular Changes on Neuroimaging criteria on pre-treatment brain MRI and automated measurements of white matter disease of MRI-fluid-attenuated inversion recovery sequences. Patients were excluded if they did not complete > 80 % of the therapy, had significant cardiac disease, medical illness, medical contraindication to having RIC performed, intracerebral hemorrhage, stroke within the past 6 months, or an alternate etiology of small vessel disease such as vasculitis, genetic disorder, > 50% stenosis of intracranial vessel, or atrial fibrillation. The difference between the RIC and placebo group was the pressure of the cuff inflation from the automated device (200 mmHg in RIC cycling for 5 cycles of inflation and deflating for 5 minutes vs. 50mmHg in control).

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.

Taking Patients Directly to Comprehensive Stroke Centers May Be Feasible for Patients and Hospitals

Neal S. Parikh, MD 

Katz BS, Adeoye O, Sucharew H, Broderick JP, McMullan J, Khatri P, et al. Estimated Impact of Emergency Medical Service Triage of Stroke Patients on Comprehensive Stroke Centers. An Urban Population-Based Study. Stroke. 2017

Whether all acute stroke patients should be taken to a comprehensive stroke center (CSC) remains unclear. However, there is mounting computer modeling and clinical data that support transporting acute stroke patients directly to CSCs, especially when the additional travel time is not excessive. The American Heart Association recommends transporting patients directly to CSCs if additional travel time does not exceed 15–20 minutes.

Brian Katz and colleagues performed an analysis to examine real-world EMS transport practices in the Greater Cincinnati/Northern Kentucky (GCNK) region. They performed computer modeling to evaluate the implications of adhering more closely to AHA recommendations. The authors identified patients with acute stroke from the GCNK Study who were transported by EMS in 2010. The GCNK region has 1 CSC and a total of 14 primary stroke centers (PSC) and acute stroke ready hospitals (ASRH). Patients’ addresses were geocoded, and software was used to estimate travel distances to each patient’s initial presenting hospital and also to the CSC.