American Heart Association

treatment

Article Commentary: “One-Year Home-Time and Mortality After Thrombolysis Compared With Nontreated Patients in a Propensity-Matched Analysis”

Jennifer Harris, MD
@JenHarrisMD

Yu AYX, Fang J, Kapral MK. One-Year Home-Time and Mortality After Thrombolysis Compared With Nontreated Patients in a Propensity-Matched Analysis. Stroke. 2019;50:3488–3493.

Thrombolytic therapy with intravenous recombinant tissue plasminogen activator (r-tPA) is an effective treatment in acute ischemic stroke. Several studies have examined functional outcome and mortality at 3 months after intravenous r-tPA treatment. However, data on long-term outcome are limited. Two randomized controlled stroke trials, the National Institute of Neurological Disorders and Stroke trial (NINDS) and the third International Stroke Trial (IST-3), have examined long-term mortality after intravenous r-tPA and revealed no differences in mortality rates among treated and nontreated patients at 12- and 18-months follow-up, respectively.

To explore long-term clinical outcome after intravenous r-tPA, Yu et al. conducted a nationwide register-based follow up study using a propensity score matching method. Using the Ontario Stroke Registry, they identified 29,036 patients with ischemic stroke and used propensity score methods to match the 4,449 patients treated with intravenous r-tPA to nontreated patients. The primary outcome was 1-year home-time, which was defined as the number of days spent outside of any healthcare institutions, and showed that compared with nontreated patients, those treated with intravenous r-tPA experienced a mean of 9.5 additional days at home in the first year. Now, while looking at these results from an individual patient perspective, this might seem like a rather small improvement; however, looking at the larger picture, it can mean significant cost savings for the healthcare system at large. With roughly 700,000 ischemic strokes occurring annually in the United States, and associated stroke care costs estimated at $34 billion each year, even a small increase in the rate of thrombolysis could potentially lead to reduced hospital stays and large costs savings.

Article Commentary: “Advances and Innovations in Aphasia Treatment Trials”

Burton J. Tabaac, MD
@burtontabaac

Berube S, Hillis AE. Advances and Innovations in Aphasia Treatment Trials. Stroke. 2019;50:2977–2984.

Aphasia is a disorder that results from damage to portions of the brain that are responsible for language. For most people, these areas reside in the left hemisphere of the brain. Aphasia usually occurs suddenly, often following a stroke or head injury, but it may also develop slowly, as the result of a brain tumor or a progressive neurological disease. The disorder impairs the expression and understanding of language, as well as reading and writing. Aphasia may co-occur with speech disorders, such as dysarthria or apraxia of speech, which also result from brain damage.1 This Stroke article summarizes advances in clinical trials of aphasia, secondary to stroke, and the treatment studied from clinical trials over the past 5 years. The authors discuss noninvasive brain stimulation, transcranial direct current stimulation, and transcranial magnetic stimulation, as well as pharmacological and medical interventions.

Drs. Berube and Hillis noted, “methodological weaknesses in many of the aphasia treatment studies compromise strong conclusions about efficacy.” Interestingly, the authors added, “The distribution of aphasia subtypes might influence efficacy … it is possible that individuals with Broca’s aphasia respond more to certain types of treatment, while those with Wernicke’s aphasia respond more to other types. However, none of the studies have been adequately powered to identify differential efficacy across subtypes.” Drs. Berube and Hillis concluded in their review that the most effective or efficient interventions currently available combine novel Speech-Language Therapy (SLT) with noninvasive brain stimulation (NIBS) or medications.

Hope for the Brokenhearted

Rachel Forman, MD

Siedler G, Sommer K, Macha K, Marsch A, Breuer L, Stoll S, et al. Heart Failure in Ischemic Stroke: Relevance for Acute Care and Outcome. Stroke. 2019.

The topic of heart failure (HF) is not uncommon in the stroke world. It is a known risk factor for stroke and is related to prothrombotic/proinflammatory states, worsening of cerebral tissue oxygenation, and hemodynamic impairment. There is also consideration if HF may affect the safety and efficacy of acute stroke therapies. Some concerns include reduced circulation after tPA with low cardiac output or difficulties with anesthesia management during MT. This study by Siedler et al. aimed to look at the effects of HF on stroke patients who received tPA, mechanical thrombectomy (MT), or both. The authors note the importance of this study and that many of the prospective clinical trials have excluded HF patients.

Patients who received tPA or MT at a university stroke center were included into a prospective registry. Patients with HF were identified based on their echocardiograms (transthoracic or transesophageal) done as a part of the stroke evaluation. The impairment of left ventricular ejection fraction (LVEF) was categorized as mild if >35% EF, moderate if 25-35% EF, and severe if <25% EF. Functional outcome was assessed after 90 days by telephone interviews and favorable outcome was considered mRS 0-2.  

Article Commentary: “Low-Dose Tirofiban Treatment Improves Neurological Deterioration Outcome After Intravenous Thrombolysis”

Wayneho Kam, MD

Wu C, Sun C, Wang L, Lian Y, Xie N, Huang S, et al. Low-Dose Tirofiban Treatment Improves Neurological Deterioration Outcome After Intravenous Thrombolysis. Stroke. 2019.

The current standard of practice is to avoid the use of antithrombotic agents within the first 24 hours after receiving intravenous thrombolytics. This is due to concern that the concurrent use of antiplatelets or anticoagulants with recent thrombolytic administration may increase the risk for bleeding events. The concern may be unfounded, however, particularly given the relatively short half-life of alteplase.

There are instances, of course, when use of such medications within 24 hours of alteplase administration may be warranted, such as with concomitant endovascular therapy with stent placement or acute myocardial infarction.

What if early neurological deterioration occurs in patients after they received tPA, in the absence of a clear explanation, such as hemorrhagic conversion or cerebral edema? Will these patients benefit from early initiation of antiplatelet therapy?

Investigating the Causes of Declining Carotid Endarterectomies

Raffaele Ornello, MD

Johal AS, Loftus IM, Boyle JR, Naylor AR, Waton S, Heikkila K, et al. Changing Patterns of Carotid Endarterectomy Between 2011 and 2017 in England: A Population-Based Cohort Study. Stroke. 2019;50:2461–2468.

Carotid endarterectomy (CEA) is effective for secondary stroke prevention in symptomatic patients, while its effectiveness in asymptomatic patients is a matter of debate. Data suggest that CEAs are declining worldwide; however, the reasons for that decline are unclear.

To investigate those possible causes, the authors reviewed data from the English National Vascular Registry in the 2011-2017 period and confirmed a decline of CEAs in both symptomatic and asymptomatic patients. In detail, CEAs performed in asymptomatic patients declined by 63%, from 722 in 2011 to 265 in 2017, while those performed in symptomatic patients declined by 25%, from 4992 in 2011 to 3482 in 2017.

Article Commentary: “Obesity-Associated Organ Damage and Sympathetic Nervous Activity: A Target for Treatment?”

Adeola Olowu, MD

Lambert EA, Esler MD, Schlaich MP, Dixon J, Eikelis N, Lambert GW. Obesity-Associated Organ Damage and Sympathetic Nervous Activity: A Target for Treatment? Hypertension. 2019;73:1150–1159.

The authors of this review focused on obesity and a potential target for treatment. Obesity and increased body mass index are risk factors for diseases such as stroke, cardiovascular disease, and other medical conditions. This brief review focused on cardiovascular studies, studies demonstrating an association between weight gain with blood pressure, cardiovascular abnormalities, renal function, and endothelial dysfunction and its relationship with biochemical sympathetic nervous activity.

Being overweight or obese is a growing medical condition worldwide. Obesity is unique to other cerebrovascular risk factors because it may be the sole risk factor an individual may have for quite some time. However, the lack of other cerebrovascular risk factors such as hypertension and diabetes does not make being overweight or obese harmless. The studies reviewed showed hypertension prevalence to be at least 16% higher in the obese population compared to the normal-weight population in the United States. Pre-hypertension was found in approximately 40% of obese men and 30% in obese women in China. Observational studies demonstrated elevated plasma norepinephrine and increased MSNA with weight gain.

By |September 30th, 2019|clinical, treatment|0 Comments

Is Triple Antithrombotic Therapy History?

Victor J. Del Brutto, MD

Knijnik L, Rivera M, Blumer V, Cardoso R, Fernandes A, Fernandes G, et al. Prevention of Stroke in Atrial Fibrillation After Coronary Stenting: Systematic Review and Network Meta-Analysis. Stroke. 2019;50:2125–2132

Approximately one-fourth of patients with atrial fibrillation (AF) have coronary artery disease (CAD), and a significant number of them undergo percutaneous coronary intervention (PCI) and stent placement. This clinical scenario represents a special circumstance in which a combined antithrombotic regimen with platelet anti-aggregation (to prevent stent thrombosis and myocardial ischemia) and anticoagulation (to prevent AF-related cardioembolic stroke) is warranted. Previously, in the absence of randomized controlled trials, guidelines supported the use of a Vitamin K antagonist (VKA) and dual antiplatelet (DAPT), especially when drug eluting stents were used. This regimen known as “triple therapy” has shown to have a fourfold risk of bleeding complications when compared to oral anticoagulation alone.

Better is the Enemy of Good

Elena Zapata-Arriaza, MD
@ElenaZaps

García-Tornel A, Requena M, Rubiera M, Muchada M, Pagola J, Rodriguez-Luna D, et al. When to Stop: Detrimental Effect of Device Passes in Acute Ischemic Stroke Secondary to Large Vessel Occlusion. Stroke. 2019;50:1781–1788

The achievement of mTICI 3 after one pass, known as first pass effect, is clearly associated with better functional outcome, as compared with those patients with more passes needed to obtain full recanalization. But how many passes should we attempt before stop procedure? Or maybe we should pursue a good (TICI 2B) but not perfect recanalization, instead of seeking TICI 3, because such recanalization is more than enough for patient outcome?

These are some of the aims of this study, in addition to finding the relation between number of passes and recanalization degree and clinical outcome.

Article Commentary: “Sphenopalatine Ganglion Stimulation to Augment Cerebral Blood Flow”

Yan Hou, MD, PhD

Bornstein NM, Saver JL, Diener HC, Gorelick PB, Shuaib A, Solberg Y, et al.. Sphenopalatine Ganglion Stimulation to Augment Cerebral Blood Flow. A Randomized, Sham-Controlled Trial. Stroke. 2019;50:00-00.

Preclinical studies have demonstrated that sphenopalatine ganglion (SPG) stimulation is a potent method to enhance collateral flow and reduce infarct size in stroke animal models. The ImpACT-24A Investigators performed a sham-controlled, randomized trial to test the efficacy and safety of SPG stimulation as a potential therapy for patients with acute anterior circulation ischemic stroke who are not eligible for reperfusion therapy.

A total of 253 patients with acute anterior circulation ischemic stroke with moderate deficit (median NIHSS of 11) within 24 hours of onset not treated with tPA or thrombectomy either received SPG (n=153) or sham (n=100) stimulation. The primary efficacy outcome is mRS improvement beyond expectation at 90 days, which was defined as an mRS score one or more points better than expected based on a prognostic model. Although SPG stimulation only showed a 9.7% higher rates of mRS improvement beyond expectations in the intention to treat population (SPG vs. sham: 49.7% vs. 40%, odd ratio 1.48, p=0.13); there was a 23% higher rate of mRS improvement beyond expectations in the subgroup of patients with confirmed cortical involvement (SPG vs. sham: 50% vs. 27%, odd ratio 2.7, p=0.03). The different beneficial effects of SPG stimulation between patients with cortical infarcts and deep subcortical infarcts was considered due to more robust collateral arterial networks in superficial leptomeningeal arteries supplying the cortical layers. SPG stimulation was not associated with any increase in serious adverse events, symptomatic intracranial hemorrhage, or mortality. Only two serious adverse events were considered possibly related to the implantation (one epistaxis and one torn extraction).

Antiplatelet Therapy in Stroke: The Old and the New

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

Hackam DG, Spence JD. Antiplatelet Therapy in Ischaemic Stroke and Transient Ischaemic Attack. Stroke. 2019; 50:773–778.

Antiplatelet therapy reduces the burden of recurrent vascular events in patients with non-cardioembolic ischaemic stroke or TIA and the authors present an overview of major trials.  The IST and CAST studies, conducted over 20 years ago, highlight the benefits of aspirin in the acute setting and the benefits of aspirin in the longer term are demonstrated by the Antithrombotic Trialists’ Collaboration.  It was later shown that aspirin and dipyridamole in combination is more effective than aspirin alone, with most data coming from the ESPS-2 and ESPRIT studies, although dipyridamole requires twice daily dosing and many patients develop headache.  The PRoFESS trial shows rates of recurrent stroke are similar with clopidogrel compared to aspirin and dipyridamole, although clopidogrel has once-daily dosing and fewer patients develop headache.

The landmark CHANCE and POINT trials demonstrate that DAPT with clopidogrel and aspirin reduces the risk of stroke and vascular events in patients with high-risk TIA or minor stroke compared to aspirin alone and the benefit is confined to the early period.  This may explain why longer-term trials of DAPT (MATCH, SPS3 and CHARISMA) found no benefit. The SOCRATES trial found that DAPT with ticagrelor and aspirin is not superior to aspirin in reducing vascular events, although ticagrelor shows a strong trend toward reduced stroke in the acute setting and is more efficacious in patients with large artery disease or patients already taking aspirin.  The THALES trial is studying ticagrelor in this context and will help to better define the role of ticagrelor in acute stroke. Importantly, we can reduce the risk of haemorrhage associated with antiplatelet therapy by effectively managing bleeding risk factors, including blood pressure control, treatment of Helicobacter pylori infection and proton pump inhibitors for high risk patients.