American Heart Association

Monthly Archives: April 2019

Dual Antiplatelet Therapy for Large Artery Atherosclerosis

Victor J. Del Brutto, MD

Kim D, Park JM, Kang K, Cho YJ, Hong KS, Lee KB, et al. Dual Versus Mono Antiplatelet Therapy in Large Atherosclerotic Stroke: A Retrospective Analysis of the Nationwide Multicenter Stroke Registry. Stroke. 2019;50:1184–1192.

Large artery atherosclerosis (LAA) is responsible for a fourth of all ischemic strokes and is the mechanism of cerebral ischemia with the highest risk of recurrence. Current evidence supports that aggressive platelet anti-aggregation is beneficial in the acute phase due to the high thrombogenicity caused by plaque rupture, while the use of statins and strict vascular risk factors control is more relevant chronically to assure plaque stability and to stop arterial disease progression. Current guidelines recommend long-term antiplatelet monotherapy for secondary stroke prevention. However, high-risk clinical settings such as coexistence of coronary artery disease, stroke recurrence despite taking one antiplatelet agent, high-degree stenosis, or presence of micorembolic signals on transcranial Doppler often lead physicians to prescribe dual antiplatelet therapy (DAPT) beyond the acute phase.

The current study used a large multicenter prospective stroke registry from Korea to compare the effectiveness of DAPT with clopidogrel plus aspirin versus aspirin monotherapy in preventing vascular events and death in patients who had an ischemic stroke or TIA attributed to LAA. At one-year follow up, combination therapy was associated with lower risk of having the composite outcome of any stroke, myocardial infarction, or all-cause death. Of notice, DAPT did not reduce the risk of stroke recurrence when compared to aspirin alone, thus results were mainly attributable to overall mortality reduction (Figure 4).

Kaplan-Meier curves for primary outcome ( A), stroke recurrence ( B), and all-cause death ( C) after stabilized inverse probability of treatment weighting in intention-to-treat, per-protocol, and as-treated populations. A indicates aspirin; and C+A, clopidogrel plus aspirin.

Figure 4. Kaplan-Meier curves for primary outcome (A), stroke recurrence (B), and all-cause death (C) after stabilized inverse probability of treatment weighting in intention-to-treat, per-protocol, and as-treated populations. A indicates aspirin; and C+A, clopidogrel plus aspirin.

By |April 30th, 2019|clinical|1 Comment

Larger Core and Lengthened Time: Farther Horizons in Stroke Thrombectomy

Elena Zapata-Arriaza, MD
@ElenaZaps

Leslie-Mazwi TM, Hamilton S, Mlynash M, Patel AB, Schwamm LH, Lansberg MG, et al. DEFUSE 3 Non-DAWN Patients: A Closer Look at Late Window Thrombectomy Selection. Stroke. 2019;50:618–625.

The recently released DEFUSE 3 and DAWN trials have demonstrated the effectiveness and safety of thrombectomy in extended time window, beyond 6 hours. However, given the restraint in inclusion criteria of the DAWN trial, the assessment of endovascular therapy in DEFFUSE 3 patients who would have been excluded for DAWN will guide us about thrombectomy effect in other subgroups.

To resolve this mentioned purpose, the authors applied eligibility criteria of the DAWN trial to DEFUSE 3 patient data to identify DEFUSE 3 patients not meeting DAWN criteria (DEFUSE 3 non-DAWN). Reasons for DAWN exclusion in DEFUSE 3 were infarct core too large, National Institutes of Health Stroke Scale (NIHSS) score 6 to 9, and modified Rankin Scale score of 2. Only 13 DEFUSE 3 patients had a prestroke mRS of 2, which was inadequate to address whether these patients had a favorable response to thrombectomy; therefore, these patients were categorized by their NIHSS score. Analysis was performed for core to large (CTL) versus core-not-too-large (CNTL) patients and for NIHSS 6 to 9 versus NIHSS ≥10 patients. Subgroups were compared with the DEFUSE 3 non-DAWN and entire DEFUSE 3 cohorts.

By |April 29th, 2019|clinical|0 Comments

Outcomes of Telestroke Patients: The “Drip-and-Stay” vs. “Drip-and-Ship” Model

Kara Jo Swafford, MD

Wysocki NA, Bambhroliya A, Ankrom C, Vahidy F, Astudillo C, Trevino A, et al. Outcomes Among Patients With Ischemic Stroke Treated With Intravenous tPA (Tissue-Type Plasminogen Activator) via Telemedicine: Is the Drip-and-Stay Model Safe? Stroke. 2019;50:895–900.

Telemedicine has expanded patient access to acute stroke treatment, including administration of intravenous (IV) tPA. It supports the “hub and spoke model,” providing immediate patient access to a stroke specialist at a remote hospital to help guide emergent treatment. After initial telemedicine consultation and administration of IV tPA, whether the safety and outcomes of transferring the patient to the hub hospital (“drip-and-ship”) or remaining at the spoke hospital (“drip-and-stay”) are similar is uncertain.

Wysocki et al. conducted an observational retrospective review of prospectively collected data from a telemedicine stroke registry. The study included patients with acute ischemic stroke who received IV tPA at one of 17 network hospitals and then either stayed or were transferred to the hub hospital. Those who had planned endovascular therapy were excluded because all were transferred to the hub hospital. Primary outcomes included in-hospital mortality, length of stay, discharge disposition, rates of symptomatic ICH, and good functional outcome based on achieving a 90-day mRS score of 0-1.

By |April 26th, 2019|clinical|0 Comments

Author Interview: Prof. Craig Anderson, MD, PhD, on “Intensive blood pressure reduction with intravenous thrombolysis therapy for acute ischaemic stroke (ENCHANTED)”

Prof. Craig Anderson

Prof. Craig Anderson

An interview with Prof. Craig Anderson, MD, PhD, Professor of Neurology and Epidemiology, University of New South Wales, about blood pressure management after intravenous thrombolysis treatment.

Interviewed by Dr. Mohammad Anadani, MD, Neurology Resident, Medical University of South Carolina.

They will be discussing the paper Intensive blood pressure reduction with intravenous thrombolysis therapy for acute ischaemic stroke (ENCHANTED): an international, randomised, open-label, blinded-endpoint, phase 3 trial, published in the February 2019 issue of The Lancet.

Dr. Anadani: First, I want to thank Prof. Anderson for agreeing to the interview. Prof. Anderson’s research has a significant impact on the stroke field and especially on our understanding of the relationship between blood pressure and outcome after hemorrhagic and ischemic stroke. Prof. Anderson was the lead investigator of the INTERACT 2 trial and the ENCHANTED trial. In this interview, we will discuss the results of the ENCHANTED trial and its implication on clinical practice.

Defining the Optimal Duration of Dual Antiplatelet Therapy after Ischaemic Stroke or Transient Ischaemic Attack

Alan C. Cameron, MB ChB, BSc (Hons), MRCP

Rahman H, Khan SU, Nasir F, Hammad T, Meyer MA, Kaluski E. Optimal Duration of Aspirin Plus Clopidogrel After Ischemic Stroke or Transient Ischemic Attack: A Systematic Review and Meta-Analysis. Stroke. 2019;50:947–953.

Through a systemic review and meta-analysis of 10 randomised trials comparing dual antiplatelet therapy (DAPT) with aspirin plus clopidogrel versus aspirin alone in over 15,000 patients with ischaemic stroke (IS) or transient ischaemic attack (TIA), Rahman and colleagues demonstrate that £1 month of DAPT reduces the relative risk of recurrent IS by almost 50% with no increase in major bleeding. In contrast, £3 months of DAPT reduces IS by 28% but increases major bleeding, whilst >3 months of DAPT does not reduce recurrent IS and increases major bleeding. The reduction in risk of recurrent IS with £3 months of DAPT may be due to substantial early benefit within the first few days or weeks. The POINT and CHANCE trials suggest maximum benefit is achieved when DAPT is initiated within the first 24 hours after minor IS or high-risk TIA, which highlights a need for services that allow patients to be reviewed within this timeframe.

The risk of bleeding was greater in aspirin naïve patients in analysis of the EXPRESS and FASTER studies, highlighting a need to screen carefully for bleeding risk factors in this group of patients. Better blood pressure control combined with screening and management of bleeding risk factors is essential to ensure benefits from antiplatelet therapy are not offset by increased bleeding. Overall, we can be confident that DAPT is most effective and safe in the early weeks after minor IS or high-risk TIA to reduce the risk of recurrence.

New Scoring System Proposed to Better Predict Outcomes for Ruptured Aneurysm Microsurgery

Kara Jo Swafford, MD

Ban VS, El Ahmadieh TY, Aoun SG, Plitt AR, Lyon KA, Eddleman C, et al. Prediction of Outcomes for Ruptured Aneurysm Surgery: The Southwestern Aneurysm Severity Index. Stroke. 2019;50:595–601.

Aneurysmal subarachnoid hemorrhage (SAH) accounts for 80% of nontraumatic SAH and is associated with high morbidity and mortality. Severity grading scales have been created, including the Hunt and Hess scale, which predict outcomes independent of treatment. Prognosis following microsurgical intervention not only depends on clinical presentation, but also aneurysm anatomy and comorbidities. The Southwestern Aneurysm Severity Index (SASI) was created to risk stratify patients with ruptured aneurysms for microsurgical treatment. SASI components include clinical features, imaging findings, aneurysm characteristics and re-operation.

Vertebral Artery Patency and Recanalization Success

Danielle de Sa Boasquevisque, MD

Boeckh-Behrens T, Pree D, Lummel N, Friedrich B, Maegerlein C, Kreiser K, et al. Vertebral Artery Patency and Thrombectomy in Basilar Artery Occlusions: Is There a Need for Contralateral Flow Arrest? Stroke. 2019;50:389–395.

Patients with basilar artery occlusion (BAO) comprise 10-20% of all large vessel occlusion cases but carry high mortality and morbidity rates, reaching up to 95% if recanalization is not achieved. The optimal approach for treatment of this life-threatening condition – including the optimal time-window – is still heavily debated. Mechanical thrombectomy is currently the standard of care for this population in most stroke centers, despite the lack of evidence compared to anterior circulation.

Studies up until now showed that some factors are related to better recanalization rates in this population and hence, better prognosis. These variables were hyperdense basilar artery, short thrombus length, early initiation of endovascular therapy and contact aspiration. Some case-reports have also suggested that anatomic and hemodynamic factors related to reversal flow and patency of vertebral arteries could affect recanalization success.

The primary objective of this study by Boeckh-Behrens et al. was to to investigate the association between low flow condition contralateral to the catheter-bearing vertebral artery and  successful recanalization post-mechanical thrombectomy (MT) in a population individuals with acute basilar artery occlusion. The authors hypothesized that patients with low flow condition defined as either aplastic or hypoplastic vertebral artery (< 50% of the dominant artery) contralateral to the catheter position have more chances to achieve complete recanalization once they have less risk of distal emboli.

All patients were subjected to digital subtraction angiography. The complete vertebrobasilar axis recanalization was defined as grade 9 (on a scale of 1 to 9), and it could be achieved with or without residual branch occlusion.

By |April 19th, 2019|clinical|0 Comments

Artificially Sweetened Beverages: Sweet Taste with Sour Consequences

Kristina Shkirkova, BSc

Mossavar-Rahmani Y, Kamensky V, Manson JE, Silver B, Rapp SR, Haring B et al. Artificially Sweetened Beverages and Stroke, Coronary Heart Disease, and All-Cause Mortality in the Women’s Health Initiative. Stroke. 2019;50(3):555-562

Consumption of Artificially Sweetened Beverages (ASB) has been associated with cardiovascular disease risks. In a cohort of postmenopausal US women from the Women’s Health Initiative Observational Study authors of the new study examined the association between ASB consumption and incidence of cardiovascular disease, including coronary heart disease, stroke, and mortality.

From among 93,676 women who were part of the Women’s Health Initiative Observational Study (WHI-OS) between 1993 and 1998, the study included 81,714 women, age 50 to 79, who provided information in their estimated ASB consumption. The mean follow-up period of all study participants was 11.9 years from the day of WHI-OS enrollment.

Stroke Thrombectomy: Further, It´s Possible

Elena Zapata-Arriaza, MD
@ElenaZaps

Compagne KCJ, van der Sluijs PM, van den Wijngaard IR, Roozenbeek B, Mulder MJHL, van Zwam WH, et al. Endovascular Treatment: The Role of Dominant Caliber M2 Segment Occlusion in Ischemic Stroke. Stroke. 2019;50:419–427.

Despite the recently demonstrated benefit of endovascular treatment (EVT) for proximal large vessel occlusion (LVO) of the anterior circulation (ICA and M1), evidence for treatment benefit of more distal occlusions, including the M2 segment of the middle cerebral artery (MCA), is limited, and further studies are necessary to address this question. In addition, the efficacy and safety of EVT in M2 occlusions remain unproven.

To determine the efficacy and safety of EVT in M2 occlusions, the authors performed an observational study with data obtained from the MR CLEAN registry. Only patients with a documented M1 or M2 target occlusion on baseline digital subtraction angiography (DSA) were included.

Caliber dominance was considered present if 1 M2 branch had a larger diameter than the other on DSA or if the perfusion defect associated with the occluded M2 branch was larger than 50% of MCA territory. Only when the diameters of both the inferior and superior branches were equal and the associated perfusion defect was ≈50% of MCA territory, the branches were considered codominant. DSA-only procedures were cases in which the target occlusion resolved or migrated too distally (M3 or M4 branches) caused by contrast flushing or manipulation with the catheter, without actual performing of intended EVT.

By |April 16th, 2019|clinical|0 Comments

Phosphodiesterase-3 Inhibitors: The New Kid on the Block

Victor J. Del Brutto, MD

Bieber M, Schuhmann MK, Volz J, Kumar GJ, Vaidya JR, Nieswandt, et al. Description of a Novel Phosphodiesterase (PDE)-3 Inhibitor Protecting Mice From Ischemic Stroke Independent From Platelet Function. Stroke. 2018;50:478–486.

Inhibition of phosphodiesterase-3 (PDE-3) in platelets increases intracellular cAMP levels resulting in blockage of platelet aggregation induced by collagen, adenosine diphosphate, arachidonic acid, and epinephrine. In addition, PDE-3 inhibitors have a pleiotropic effect over blood vessels, which include arteriolar vasodilation, endothelial repair, smooth muscle anti-proliferative effect, and reduction of endothelial inflammatory response.

Although considered to have a central antiplatelet mechanism of action, PDE-3 inhibitors exert its vascular protective effect through the diverse therapeutic targets listed above. Cilostazol, a PDE-3 inhibitor prototype, is often used chronically in patients with peripheral vascular disease, as well as for coronary artery disease and stroke secondary prevention, particularly in Asian countries. There is growing evidence on the long-term efficacy and safety of cilostazol used among patients with non-cardioembolic stroke, especially when used in combination with aspirin or clopidogrel. However, little is known about its neuroprotective effects during acute ischemic injury.