In the past two decades, we have seen major advances in the treatment of transient ischemic attack (TIA) and acute ischemic stroke. Unfortunately, these advances have not benefited the majority of TIA and stroke patients. Reasons vary and include the failure of patients and providers to recognize the severity of early symptoms, resulting in critical delays in treatment. Other reasons include the inability of isolated emergency departments (EDs) to acquire life-saving technology or enhance provider expertise in recent medical advances. Effective treatment of TIA and stroke requires an integrated, systematic approach that begins in the ED, continues in the inpatient setting, and is maintained after discharge.
Stroke is the third most common cause of mortality and a leading cause of disability in the US.1 Unfortunately, many patients have not benefited from the advances in stroke treatment that have occurred over the past 20 years. Although the figures vary by institution, only an estimated 2–11% of patients who qualify for tissue-type plasminogen activator (tPA) receive it during an acute ischemic stroke.2,3
One reason for the under-use of advanced treatments may be that the symptoms associated with transient ischemic attack (TIA) and stroke are not always recognized as serious. In addition, many patients seek medical attention after they have missed the window of treatment opportunity. Another possible contributor to under-use of advanced treatments is that advanced stroke intervention requires the expertise of vascular neurologists and neurointerventionalists, which is not readily available in many emergency departments (EDs). Effective treatment of TIA and stroke requires a rapid, integrated, systematic approach, beginning with arrival of the patient at the ED and continuing with acute and subacute management in the inpatient setting through to long-term management to prevent secondary strokes.
Emergency Department Management of Acute Stroke and Transient Ischemic Attack
Acute management of TIA and stroke in the ED requires rapid assessment, diagnostic testing, neuroimaging, thrombolysis or thrombectomy if indicated, early antithrombotic intervention, dedicated neurologic monitoring, and supportive care.
Diagnosing Transient Ischemic Attack versus Stroke.TIA is currently defined as “a transient episode of neurological dysfunction caused by focal brain, spinal cord, or retinal ischemia, without acute infarction.”4 This new definition distinguishes itself from previous definitions in that there is no longer an arbitrary cut-off time (24 hours) after which a TIA would be considered a stroke.4
Although TIAs do not result in infarction and typically resolve quickly, they are not benign and must be treated as an emergency that could lead to stroke. Between 10 and 15% of patients who have a TIA will have a stroke within three months; half of these will occur within 48 hours.4 Prompt diagnosis and management of TIA may reduce future stroke rates. In one study, the risk dropped from 10.3% (32/310) to 2.1% (6/281) when median time to diagnosis decreased from three days to one day and the median time to first prescription decreased from 20 days to one day.5 In another study, rapid assessment and treatment in TIA triage units achieved a 90-day stroke rate of 1.24% (95% confidence interval [CI] 0.72–2.12) compared with a predicted stroke rate of 5.96%.6 These studies demonstrate that rapid initiation of treatment in patients having TIA may reduce the risk for stroke.5,6
To improve the speed of clinical assessment, diagnosis, and early management decisions for patients with TIA or stroke, a dedicated stroke team and protocol can be useful.7 Initial clinical assessment should be performed by physicians in the ED.7 The ABCD2 score, which considers age, blood pressure, clinical features, duration of symptoms, and diabetes history, predicts short-term stroke recurrence and can be key for helping ED physicians rapidly assess patients with suspected TIA or stroke.8,9 In addition, the National Institutes of Health Stroke Scale (NIHSS) provides information regarding the severity of the stroke.7
In general, the diagnostic studies performed when a patient presents to the ED with TIA or stroke include magnetic resonance imaging (MRI) with diffusion-weighted imaging or MR angiography of the head and neck to identify areas of ischemia that confirm stroke.4 Carotid artery sonography or transcranial Doppler may be used to determine whether a carotid lesion or extracranial source is responsible for symptoms.4 If a cardioembolic source is suspected, a transthoracic echocardiogram or a transesophageal echocardiogram may be performed. A hypercoagulable work-up may be warranted in a younger patient with no vascular risk factors and absence of other causes.4
Emergency Treatment of Acute Ischemic Stroke. Once a patient receives a diagnosis of acute ischemic stroke, a determination as to whether the patient qualifies for thrombolytic therapy needs to be made.10 Although use of intravenous (IV) tPA within 90 minutes of stroke onset is best, many patients benefit when treatment is initiated within 91–180 minutes.11 Recent results of the European Cooperative Acute Stroke Study (ECASS) III, a randomized trial, indicated that improved outcomes were achieved even in stroke patients who received IV tPA up to 4.5 hours after stroke onset.12 In the US, IV tPA is approved for treatment of acute ischemic stroke within three hours of onset in a broad spectrum of patients (see Table 1). When administered within three hours, IV tPA is effective at three months for the following outcome measures: Barthel Index, modified Rankin Scale, Glasgow Outcome Scale, and the NIHSS.11 In addition, patients treated with tPA are at least 30% more likely to have minimal or no disability at three months.11
Safety concerns with IV tPA were summarized in a meta-analysis of 15 open-label studies.13 The most common adverse effect of tPA is intracerebral hemorrhage (ICH), which occurs in 5.2–6.4% of patients.11,13 Other adverse effects are rare and include systemic bleeding, myocardial rupture, anaphylaxis, and angioedema.7 A recent report compared the rate of symptomatic ICH after IV tPA in patients receiving antiplatelet therapy at the time of their stroke.14 This prospective audit of the Safe Implementation of Treatments in Stroke-Monitoring Study (SITS) data showed that, compared with patients not receiving antiplatelet therapy prior to stroke onset, those receiving antiplatelet therapy had an absolute excess of symptomatic ICH of 1.4%, which was not associated with poor functional outcomes or higher mortality rates at three months. Of all antiplatelet therapy groups (aspirin, clopidogrel, aspirin + clopidogrel, dipyridamole, aspirin + dipyridamole, and ‘others’), the combination of aspirin + clopidogrel was a significant predictor of symptomatic ICH compared with antiplatelet-naive patients as per National Institute of Neurological Disorders and Stroke (NINDS) definition (odds ratio [OR] 1.74, 95% CI 1.11–2.73; p=0.0167) and ECASS II definition (OR 2.11, 95% CI 1.29–3.45; p=0.0031). Although thrombolysis is not contraindicated in patients receiving antiplatelet therapy, caution is warranted in those receiving aspirin + clopidogrel.14
Common reasons for not qualifying for tPA are contraindications to systemic exposure to fibrinolytic agents and being outside the time window for treatment. Patients with moderate to severe strokes (NIHSS ≥10) often have persistent major arterial occlusions and poorer outcomes.15 Such patients may qualify for intra-arterial (IA) thrombolytic agents. Criteria for use of these agents include middle cerebral artery (MCA) occlusion, treatment within six hours of stroke onset, and treatment at a stroke center.7
Research is being conducted on the combined use of IV/IA tPA to treat acute ischemic stroke. The Interventional Management of Stroke (IMS) trials achieved higher rates of early, successful reperfusion using IV/IA tPA in patients with moderate to severe strokes (NIHSS ≥10).15 IMS I showed that low-dose IV tPA followed by IA tPA via standard microcatheter may be more effective than standard IV tPA for moderate to severe strokes, with a similar safety profile.15,16 The mortality rate for the IMS treatment group (16%, 13/80) was not statistically different from that of the IMS placebo group (24%, 50/211) nor from that of the IV tPA-treated patients of the NINDS trial (21%, 39/182).16 IMS II had a similar design to IMS I but included the use of the EKOS small-vessel ultrasound infusion system (EKOS Corporation, Bothell, WA), which employs a microcatheter and ultrasonic energy source to facilitate access of the tPA to the thrombus.17
IMS II had a mortality rate of 16% (13/81) and significantly better outcomes than the placebo group in the NINDS standard tPA trial,17 providing support for further research into combined IV/IA tPA treatment. IMS III aims to determine whether IV/IA tPA is superior to standard IV tPA in subjects with moderate to severe strokes.15
Some large-vessel occlusions may not respond to IV tPA and may require mechanical removal of the clot. The Merci Retrieval System® (Concentric Medical, Inc., Mountain View, CA) is a mechanical clot-removal device for large-vessel occlusions.18–20 It consists of a balloon-guided microcatheter system that includes a coil-shaped retrieval device.20 The Merci device may be used in addition to IV tPA for occlusions of the proximal MCA/internal carotid artery or the basilar artery.18,19 The device should be used as early as possible, but successful results have been reported as late as 36 hours after stroke onset.21
In the Mechanical Embolus Removal in Cerebral Ischemia (MERCI) I trial, patients (n=141) with stroke onset between three and eight hours, or with duration of nought to three hours with a contraindication for IV tPA and with treatable vessels, were treated with the Merci Retrieval System to restore blood flow.22 Recanalization was observed in 48% (68/141; p<0.0001) of patients.22 At 90 days, a favorable outcome (modified Rankin score ≤2) was seen in 36.4% of the recanalized patients and in 22% of all Merci-treated patients.22
The Multi MERCI trial uses a family of Merci devices that differ in terms of coil shape. In this ongoing trial, 164 patients with occlusion locations similar to those of the patients in the MERCI trial underwent the procedure.18 Twenty-nine percent of patients failed to recanalize following IV tPA pre-treatment; 55% recanalized following use of the Merci devices.18 At 90 days, the mortality rate was 34% and the rate of symptomatic ICH was 9.8%.18 More than one-third of patients (36%) had a modified Rankin score ≤2.18
In another ongoing trial, Merci Retriever and REcanalization of Stroke Clots Using Embolectomy (MR RESCUE), diffusion–perfusion MRI is being used to select candidates for Merci.23 Plans are for this phase II trial to include 120 patients in 30 treatment centers and to allow patients to be treated up to eight hours after stroke onset.23 Imaging will assist clinicians in identifying and targeting the penumbra, where there is the best chance of ischemia recovery. It is hoped that this will result in better outcomes by identifying patients who have potential for recovery of brain tissue after clot removal.
Another mechanical clot removal system, the Penumbra System® (Penumbra, Inc., Alameda, CA), provides two options for removal of an occlusion. The thrombus may be aspirated using a vacuum connected to a reperfusion catheter. If the thrombus cannot be aspirated, it may be directly removed using a ring attached to the catheter.24 The vacuum may assist in minimizing or avoiding unwanted embolization during recanalization. Similar to the Merci device, the Penumbra system is used in patients who have either passed the window for IV tPA or are not eligible for or are refractory to IV tPA.24 In the Penumbra pivotal trial (n=125), recanalization occurred in 81.6% of patients.24 At 90 days, the mortality rate was 32.8% (41/125) and the rate of symptomatic ICH was 11.2% (14/125).24 Twenty-five percent of patients (31/125) had a modified Rankin score ≤2.24
Finally, the Neuroflo™ catheter (CoAxia, Inc., Maple Grove, MN), a device that redirects blood flow to the brain by partially occluding aortic blood flow via a balloon, is being studied in a prospective, controlled, randomized, single-blind, multicenter trial. Investigators are comparing NeuroFlo treatment plus standard medical management versus standard medical management alone.25
Inpatient Management of Transient Ischemic Attack and Acute Ischemic Stroke
Following diagnosis and initial management of TIA or acute stroke in the ED, patients should be admitted as an inpatient. This is important because there is a higher risk for neurologic worsening or the development of complications in the first 24–48 hours following TIA or stroke.7
Antiplatelet Therapy. Antiplatelet therapy has been shown to aid in recurrent stroke prevention.7 Typically, aspirin 325mg is started within 24 hours of stroke or TIA onset in patients who have not been treated with tPA. In patients treated with tPA, aspirin 325mg should be delayed until 24 hours after thrombolytic therapy.7
Blood Pressure Control. Clinical studies have provided ambiguous data regarding blood pressure (BP) control during the acute phase of ischemic stroke.7,26 During the acute phase, the normal cerebral regulation of BP may be disrupted, leading to a direct relationship between mean arterial pressure (MAP) and cerebral blood flow (CBF). In the setting of stroke, CBF may be low or at risk for becoming inadequate, and treatment to lower BP may compound this condition and create dangerously low CBF.
Therefore, BP control should begin after the acute phase of stroke or TIA, usually defined as five to seven days. In patients not receiving IV tPA, American Heart Association (AHA)/American Stroke Association (ASA) guidelines recommend that emergency administration of antihypertensive agents should not be made during the acute stroke phase unless systolic BP (SBP) is >220mmHg or diastolic BP (DBP) is >120mmHg.7 In patients with elevated BP but who are otherwise candidates for IV tPA, BP may be lowered to allow for IV tPA (SBP ≤185mmHg; DBP ≤110mmHg); however, BP should be stable before IV tPA administration. Moreover, BP should be maintained at <180/105mmHg for the first 24 hours after IV tPA treatment.7 Excessively high BP may be associated with risk for symptomatic ICH.
Secondary Stroke Prevention in the Inpatient and Outpatient Settings
Secondary stroke prevention begins in the inpatient setting and continues after discharge. AHA and ASA guidelines recommend considering TIA and stroke similarly regarding secondary stroke prevention.4 Many risk factors are modifiable and should be part of a comprehensive effort to prevent future stroke. Some risk factors can be medically treated: hyperlipidemia, diabetes, hypertension, and heart disease (e.g. myocardial infarction [MI], atrial fibrillation). Others, such as cigarette smoking, physical inactivity, obesity, excessive alcohol use, and amphetamine use, are diet- and lifestyle-related. A summary of secondary stroke prevention components is presented in Table 2.
Antiplatelet Therapy. A key component of secondary stroke prevention is antiplatelet therapy; the type varies depending on whether the TIA or stroke was cardioembolic or non-cardioembolic. Cardioembolic stroke can result from non-valvular atrial fibrillation or left ventricular mural thrombus. Anticoagulation therapy, such as warfarin, may be recommended in many cardioembolic patients with atrial fibrillation, acute MI, left ventricular thrombus, cardiomyopathy, or valvular heart disease.27 In some cases, aspirin may be included adjunctly or in lieu of warfarin when patients are unable to take warfarin.27
In patients with non-cardioembolic ischemic stroke or TIA, AHA/ASA guidelines recommend antiplatelet agents, not oral anticoagulation, to reduce the risk for recurrent stroke and other cardiovascular events.28 Several landmark trials have been published that assist in understanding the benefits of antiplatelet therapy for secondary stroke prevention.
The Chinese Acute Stroke Trial (CAST), a large (n=21,106) randomized, placebo-controlled trial, investigated the effects of oral aspirin 160mg/day started within 48 hours of stroke onset and continued for four weeks.29 The aspirin group had a 3.3% mortality rate compared with the placebo group (3.9%; two-sided p=0.04),29 representing a 14% improvement in mortality attributable to aspirin.29 Significantly fewer ischemic and slightly more hemorrhagic strokes occurred in aspirin-treated versus placebo-treated patients (ischemic: 167/10,335 versus 215/10,320, respectively, two-sided p=0.01; hemorrhagic: 115/10,335 versus 93/10,320, respectively, two-sided p>0.1).29
The International Stroke Trial (IST), a large (n=19,435) randomized, open-label trial, studied heparin alone or in combination with aspirin.30 Heparin 500IU or 12,500IU twice daily for up to 14 days after acute stroke onset did not provide a significant outcomes advantage within 14 days or at six months after the event. Although aspirin was associated with fewer deaths within 14 days (872/9,719 versus 909/9,714) and with a smaller percentage of dead or dependent patients at six months (61.2 versus 63.5%), the differences were not significant. Patients receiving aspirin had fewer ischemic strokes in the first 14 days compared with those not receiving aspirin (2.8 versus 3.9%, two-sided p<0.001) with no difference in hemorrhagic strokes (0.9 versus 0.8%).30
The Second European Stroke Prevention Study (ESPS-2), a randomized, double-blind, placebo-controlled trial, studied the use of aspirin 50mg/day and/or extended-release dipyridamole (ER-DP) 400mg/day versus placebo in stroke or TIA patients (n=6,602) to prevent secondary stroke.31 Both aspirin and ER-DP had similar efficacy in preventing secondary stroke: OR 0.79, 95% CI 0.65–0.97 and OR 0.81, 95% CI 0.67–0.99, respectively.31 The effects of aspirin and ER-DP were additive and significantly reduced the risk for future strokes (OR 0.59, 95% CI 0.48–0.73) and for strokes and/or death (OR 0.71, 95% CI 0.59–0.84) compared with either agent alone.31
The European/Australasian Stroke Prevention in Reversible Ischemia Trial (ESPRIT), a randomized, controlled trial, assigned patients (n=2,739) with a history of TIA or minor stroke of presumed arterial origin in the past six months to aspirin 30–325mg/day with or without dipyridamole 200mg twice daily.32 The primary outcome was defined as death from all vascular causes: non-fatal stroke, non-fatal MI, or non-fatal bleeding complications.32 The hazard ratio for the effect of combination therapy compared with aspirin on primary outcome was 0.80 (95% CI 0.66–0.98).32 This result supported the findings of the ESPS-2 trial.
Recently, the Early treatment with aspirin plus extended-release dipyridamole for transient ischaemic attack or ischaemic stroke within 24 hours of symptom onset (EARLY) trial demonstrated similar safety/efficacy outcomes with aspirin plus dipyridamole therapy initiated within 24 hours compared with seven days from stroke onset in patients not receiving tPA.33 At 90 days, 56% (154/283) of patients beginning therapy early compared with 52% (133/260) of those beginning therapy at seven days had no to mild disability. Similarly, no statistical difference was detected between the groups in terms of the composite end-point (non-fatal stroke, TIA, non-fatal MI, major bleeding complications, and mortality): 28/283 in the early group and 38/260 in the late-initiation group.33
The Warfarin–Aspirin Recurrent Stroke Study (WARSS) was a randomized, multicenter, double-blind trial comparing warfarin and aspirin in 2,206 patients who had a non-cardioembolic ischemic stroke within 30 days.34 It failed to detect any difference between aspirin (325mg) and warfarin (international normalized ratio [INR] range 1.4–2.8) in preventing death from any cause or recurrent ischemic stroke.34
The Warfarin–Aspirin Symptomatic Intracranial Disease (WASID) trial compared aspirin 1,300mg/day with warfarin 5mg/day in patients with confirmed intracranial arterial stenosis within the past 90 days.35 The trial was stopped because of safety concerns. During a mean follow-up period of 1.8 years, the rates of death (4.3 versus 9.7%; p=0.02) and major hemorrhage (3.2 versus 8.3%; p=0.01) were significantly greater in the warfarin group compared with the aspirin group.35 The researchers concluded that warfarin was associated with higher rates of adverse events and afforded no benefit over aspirin.35
The Clopidogrel Versus Aspirin in Patients at Risk of Ischemic Events (CAPRIE) trial compared the safety and tolerability of clopidogrel and aspirin in patients (n=19,185) with atherosclerotic disease manifested as ischemic stroke, MI, or symptomatic peripheral artery disease.36 In this trial, clopidogrel significantly reduced the combined risk for ischemic stroke, MI, or vascular death by 8.7% compared with aspirin (p=0.043).36
The Management of Atherothrombosis With Clopidogrel in High-Risk Patients (MATCH) trial, a randomized, double-blind, placebo-controlled study, assessed whether clopidogrel 75mg/day plus aspirin 75mg/day provided improved prevention of vascular events compared with clopidogrel 75mg/day alone.37 Patients were eligible for the study if they had a TIA or ischemic stroke within the previous three months prior to randomization and had one or more of the five additional vascular risk factors—prior ischemic stroke, MI, stable or unstable angina pectoris, diabetes, or symptomatic peripheral arterial disease—within the previous three years.37 A total of 7,599 patients at high risk for stroke were randomized to receive either 75mg/day aspirin or placebo; both groups received 75mg/ day clopidogrel. Major and life-threatening hemorrhages were greater with combination treatment compared with clopidogrel alone: 2 versus 1% (p<0.0001) and 2.6 versus 1.3% (p<0.0001), respectively.37 No significant difference was detected between groups for the primary outcome (first occurrence of recurrent stroke, MI, vascular death, or re-hospitalization for acute ischemic event): 16% combination therapy versus 17% clopidogrel alone.37
Similar to the MATCH trial, the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance (CHARISMA) trial investigated the combination of aspirin 75–162mg/day plus clopidogrel 75mg/day compared with aspirin alone in high-risk patients (n=15,603).38 Patients had either clinically evident cardiovascular disease or multiple risk factors.38 Approximately 25% of patients had a history of stroke.35 As with the MATCH trial, no significant benefit was seen with combination therapy compared with monotherapy; however, the rate of moderate bleeding was significantly greater with combination therapy (2.1 versus 1.3%; p<0.001).38 The investigators concluded that the combination of aspirin and clopidogrel provides no efficacy advantage but confers considerable bleeding risk. Current guidelines specify that these drugs should not be used in combination in post-ischemic stroke and TIA patients.
The Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) trial was a randomized, 2x2 factorial, blinded study comparing aspirin 25mg plus ER-DP 200mg twice daily versus clopidogrel 75mg/day plus either telmisartan 75mg/day or placebo for prevention of recurrent stroke in patients (n=20,332) who had ischemic stroke within the previous 90 days.39 For the mean follow-up of 2.5 years, the incidence of recurrent stroke was similar in both groups: 9.0% with aspirin/ER-DP and 8.8% with clopidogrel.39 Although mean BP was 3.8/2.0mmHg lower in patients receiving telmisartan, no significant difference was detected in stroke recurrence (8.7% in the telmisartan group versus 9.2% in the placebo group).40
Lipid Therapy. As mentioned earlier, hyperlipidemia is a modifiable risk factor for TIA and ischemic stroke. In the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial, patients with recent stroke or TIA and without coronary heart disease (n=4,731) had a lower incidence of recurrent stroke (11.2 versus 13.1%; p<0.03, absolute risk reduction of 2.2% over a median of 4.9 years) and of cardiovascular events (22.4 versus 29.0%; p<0.001) when receiving 80mg/day of atorvastatin compared with placebo.41 A concern with the SPARCL trial is that repeatedly high liver enzyme levels were observed in 55 patients receiving atorvastatin compared with 11 of those receiving placebo (p<0.001).28,41,42 It is also unclear from the SPARCL trial whether the findings were the result of a class effect or specific to atorvastatin. With no data to the contrary, the effects are assumed to be associated with the drug class.28 Based on these results, statin therapy with intensive, lipid-lowering effects is recommended in patients with atherosclerotic ischemic stroke or TIA and without known coronary heart disease to reduce the risk for stroke and cardiovascular events.28
Antihypertensive Therapy. AHA/ASA guidelines recommend antihypertensive therapy after the hyperacute phase following stroke or TIA for all patients, regardless of history of hypertension.27 Because many lifestyle factors influence hypertension, behavioral change should be included as part of a comprehensive regimen.27 In general, a reduction of 10/5mmHg appears beneficial. Normal BP levels have been defined in the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) as <120/80mmHg.27,43 It remains unclear whether any particular antihypertensive drug or class offers any benefit over others, but data support the use of diuretics and the combination of diuretics and an angiotensin-converting enzyme inhibitor (ACEI).27
The Perindopril Protection Against Recurrent Stroke Study (PROGRESS) study, a randomized, double-blind trial with 6,105 hypertensive and non-hypertensive patients with history of stroke or TIA, aimed to determine the effects of BP lowering on prevention of secondary stroke.44 Patients received the ACEI perindopril 4mg/day (with diuretic indapamide at the physician’s discretion) or placebo.44 The mean BP lowering of 9/4mmHg was associated with a significant benefit in prevention of recurrent stroke: 10% recurrent stroke rate in the treated group compared with 14% in the placebo group (p<0.0001).44
An Integrated, Systematic Approach
An integrated, systematic approach that incorporates guideline-driven protocols can increase the percentage of patients receiving thrombolytic therapy. In one community study, educating the public to respond quickly to stroke symptoms raised the use of tPA from 7% in a comparison community to 14% in the intervention community.2 The use of tPA then increased to 52% compared with 6% in the comparison community after a medical professional educational campaign that included development of ED protocols for stroke.2 At another larger community hospital, establishment of a primary stroke center significantly increased the use of tPA in ischemic stroke patients from 1.5 to 10.5% during a two-year period (p<0.0001).45
The Joint Commission, in collaboration with the ASA, designates primary stroke centers based on recommendations by the Brain Attack Coalition.46 The standardized measures for stroke at primary stroke centers are shown in Table 3. Many of the criteria used by the Joint Commission to certify primary stroke centers have been associated with a significant increase in the use of tPA.3 These criteria include care protocols, integrated emergency medical services, organized EDs, and continuing medical education in stroke.
Telemedicine is a method for extending the expertise of stroke center staff to physically remote areas.47 In the typical scenario, once a potential stroke or TIA victim is identified in the ED, the ED physician performs the initial assessment and work-up while the ‘telestroke’ system is activated. The ED physician and patient are then connected via live video feed to a stroke specialist.48 In one telestroke system, the number of patients treated with IV tPA in the networked hospitals was 5% (n=80) compared with 0% (n=4) in control hospitals.47,49 Fewer telestroke patients died, were institutionalized, or were disabled at three months compared with non-telestroke patients (44 versus 54%).49
Recent advances in treating TIA and acute ischemic stroke provide new hope for patients in terms of recovery and secondary stroke prevention. Currently, IV tPA remains the only therapy that has a proven long-term outcome benefit in acute stroke treatment. However, advances in diagnosis and management have improved recanalization rates and reperfusion. Although improved recanalization does not necessarily lead to improved outcome, these advanced therapies and interventions offer promise.
Because many of the treatments require early intervention to preserve brain tissue, rapid assessment to determine whether the treatments are indicated is critical. After the acute phase of treatment, ongoing care is required to prevent secondary strokes. Key preventive approaches include antiplatelet therapy and reduction of modifiable medical, behavioral, and lifestyle risk factors.
This work was supported by Boehringer Ingelheim Pharmaceuticals, Inc (BIPI). Writing and editorial assistance was provided by Tracy E Bunting-Early, PhD, of Publication CONNEXION (Newtown, PA), which was contracted by BIPI for these services. The author meets criteria for authorship as recommended by the International Committee of Medical Journal Editors (ICMJE), was fully responsible for all content and editorial decisions, and was involved at all stages of manuscript development. The author received no compensation related to the development of the manuscript.
- Lloyd-Jones D, Adams R, Carnethon M, et al., Heart disease and stroke statistics—2009 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee, Circulation, 2009;119:e21–181.
- Morgenstern LB, Staub L, Chan W, et al., Improving delivery of acute stroke therapy: the TLL Temple Foundation Stroke Project, Stroke, 2002;33:160–6.
- Douglas VC, Tong DC, Gillum LA, et al., Do the Brain Attack Coalition’s criteria for stroke centers improve care for ischemic stroke?, Neurology, 2005;64:422–7.
- Easton JD, Saver JL, Albers GW, et al., Definition and evaluation of transient ischemic attack: a scientific statement for healthcare professionals from the American Heart Association/American Stroke Association Stroke Council; Council on Cardiovascular Surgery and Anesthesia; Council on Cardiovascular Radiology and Intervention; Council on Cardiovascular Nursing; and the Interdisciplinary Council on Peripheral Vascular Disease. The American Academy of Neurology affirms the value of this statement as an educational tool for neurologists, Stroke, 2009;40:2276–93.
- Rothwell PM, Giles MF, Chandratheva A, et al., Effect of urgent treatment of transient ischaemic attack and minor stroke on early recurrent stroke (EXPRESS study): a prospective population-based sequential comparison, Lancet, 2007;370:1432–42.
- Lavallée PC, Meseguer E, Abboud H, et al., A transient ischaemic attack clinic with round-the-clock access (SOS-TIA): feasibility and effects, Lancet Neurol, 2007;6:953–60.
- Adams HP Jr, del Zoppo G, Alberts MJ, et al., Guidelines for the early management of adults with ischemic stroke: a guideline from the American Heart Association/American Stroke Association Stroke Council, Clinical Cardiology Council, Cardiovascular Radiology and Intervention Council, and the Atherosclerotic Peripheral Vascular Disease and Quality of Care Outcomes in Research Interdisciplinary Working Groups: the American Academy of Neurology affirms the value of this guideline as an educational tool for neurologists, Stroke, 2007;38:1655–1711.
- Johnston SC, Rothwell PM, Nguyen-Huynh MN, et al., Validation and refinement of scores to predict very early stroke risk after transient ischaemic attack, Lancet, 2007;369:283–92.
- Josephson SA, Sidney S, Pham TN, et al., Higher ABCD2 score predicts patients most likely to have true transient ischemic attack, Stroke, 2008;39:3096–8.
- National Stroke Association Web Site. Guidelines for the Management of TIA. Available at: www.stroke.org/site/DocServer/TIA_Guidelines_070506_sm.pdf?docID=2361 (accessed December 4, 2009).
- National Institute of Neurological Disorders and Stroke Rt-PA Study Group, Tissue plasminogen activator for acute ischemic stroke, N Engl J Med, 1995;333:1581–7.
- Hacke W, Kaste M, Bluhmki E, et al.; ECASS Investigators, Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke, N Engl J Med, 2008;359:1317–29.
- Graham GD, Tissue plasminogen activator for acute ischemic stroke in clinical practice: a meta-analysis of safety data, Stroke, 2003;34:2847–50.
- Diedler J, Ahmed N, Sykora M, et al., Safety of intravenous thrombolysis for acute ischemic stroke in patients receiving antiplatelet therapy at stroke onset, Stroke, 2010;41:288–94.
- Khatri P, Hill MD, Palesch YY, et al.; Interventional Management of Stroke III Investigators, Methodology of the Interventional Management of Stroke III Trial, Int J Stroke, 2008;3:130–7.
- IMS Study Investigators, Combined intravenous and intra-arterial recanalization for acute ischemic stroke: the Interventional Management of Stroke Study, Stroke, 2004;35:904–11.
- IMS Trial II Investigators, The Interventional Management of Stroke (IMS) II Study, Stroke, 2007;38:2127–35.
- Smith WS, Sung G, Saver J, et al., Mechanical thrombectomy for acute ischemic stroke: final results of the Multi MERCI trial, Stroke, 2008;39(4):1205–12.
- Clarencon F, Blanc R, Gallas S, et al., Thrombectomy for acute basilar artery occlusion by using double Merci retriever devices and bilateral temporary vertebral artery flow reversal.: technical note, J Neurosurg, 2009;111:53–6.
- Stroke Trials Registry, MERCI, Internet Stroke Center website. Available at: www.strokecenter.org/trials/trialDetail.aspx?tid=619 (accessed December 4, 2009).
- Noufal M, Schmidley JW, Erdem E, Keyrouz SG, Basilar artery occlusion treated with mechanical thrombectomy beyond eight hours with successful recanalization and good functional outcomes, Cerebrovasc Dis, 2009;27:614–15.
- Smith WS, Sung G, Starkman S, et al.; MERCI Trial Investigators, Safety and efficacy of mechanical embolectomy in acute ischemic stroke: results of the MERCI trial, Stroke, 2005;36:1432–8.
- Stroke Trials Registry, MR RESCUE, Internet Stroke Center website. Available at: www.strokecenter.org/trials/trialDetail. aspx?tid=559 (accessed December 4, 2009).
- Penumbra Pivotal Stroke Trial Investigators, The penumbra pivotal stroke trial: safety and effectiveness of a new generation of mechanical devices for clot removal in intracranial large vessel occlusive disease, Stroke, 2009;40:2761–8.
- Stroke Trials Registry, SENTIS, Internet Stroke Center website. Available at: www.strokecenter.org/trials/TrialDetail.aspx?tid=618 (accessed December 4, 2009).
- Brott T, Bogousslavsky J, Treatment of acute ischemic stroke, N Engl J Med, 2000;343:710–22.
- Sacco RL, Adams R, Albers G, et al., Guidelines for prevention of stroke in patients with ischemic stroke or transient ischemic attack: a statement for healthcare professionals from the American Heart Association/American Stroke Association Council on Stroke: cosponsored by the Council on Cardiovascular Radiology and Intervention: the American Academy of Neurology affirms the value of this guideline, Stroke, 2006;37:577–617.
- Adams RJ, Albers G, Alberts MJ, et al., Update to the AHA/ASA recommendations for the prevention of stroke in patients with stroke and transient ischemic attack, Stroke, 2008;39:1647–52.
- CAST (Chinese Acute Stroke Trial) Collaborative Group, CAST: randomised placebo-controlled trial of early aspirin use in 20 000 patients with acute ischaemic stroke, Lancet, 1997;349:1641–9.
- International Stroke Trial Collaborative Group, The International Stroke Trial (IST): a randomised trial of aspirin, subcutaneous heparin, both, or neither among 19435 patients with acute ischaemic stroke, Lancet, 1997;349:1569–81.
- Diener HC, Cunha L, Forbes C, et al., European Stroke Prevention Study 2: dipyridamole and acetylsalicylic acid in the secondary prevention of stroke, J Neurol Sci, 1996;143:1–13.
- ESPRIT Study Group, Aspirin plus dipyridamole versus aspirin alone after cerebral ischaemia of arterial origin (ESPRIT): randomised controlled trial, Lancet, 2006;367:1665–73.
- Dengler R, Diener HC, Schwartz A, et al., Early treatment with aspirin plus extended-release dipyridamole for transient ischaemic attack or ischaemic stroke within 24 h of symptom onset (EARLY trial): a randomised, open-label, blinded-endpoint trial, Lancet Neurol, 2010;9:159–66.
- Mohr JP, Thompson JL, Lazar RM, et al.; Warfarin-Aspirin Recurrent Stroke Study Group, A comparison of warfarin and aspirin for the prevention of recurrent ischemic stroke, N Engl J Med, 2001;345:1444–51.
- Chimowitz MI, Lynn MJ, Howlett-Smith H, et al.; Warfarin-Aspirin Symptomatic Intracranial Disease Trial Investigators. Comparison of warfarin and aspirin for symptomatic intracranial arterial stenosis, N Engl J Med, 2005;352:1305–16.
- Harker LA, Boissel JP, Pilgrim AJ, Gent M; CAPRIE Steering Committee and Investigators, Comparative safety and tolerability of clopidogrel and aspirin: results from CAPRIE, Drug Saf, 1999;21:325–35.
- Diener HC, Bogousslavsky J, Brass LM, et al.; MATCH Investigators, Aspirin and clopidogrel compared with clopidogrel alone after recent ischaemic stroke or transient ischaemic attack in high-risk patients (MATCH): randomised, double-blind, placebo-controlled trial, Lancet, 2004;364:331–7.
- Bhatt DL, Fox KA, Hacke W, et al.; CHARISMA Investigators, Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events, N Engl J Med, 2006;354:1706–17.
- Sacco RL, Diener HC, Yusuf S, et al.; PRoFESS Study Group, Aspirin and extended-release dipyridamole versus clopidogrel for recurrent stroke, N Engl J Med, 2008;359:1238–51.
- Yusuf S, Diener HC, Sacco RL, et al.; PRoFESS Study Group, Telmisartan to prevent recurrent stroke and cardiovascular events, N Engl J Med, 2008;359:1225–37.
- Amarenco P, Bogousslavsky J, Callahan A 3rd, et al.; Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) Investigators, High-dose atorvastatin after stroke or transient ischemic attack, N Engl J Med, 2006;355:549–59.
- Cohen JS, Statin therapy after stroke or transient ischemic attack, N Engl J Med, 2006;355:2368.
- Chobanian AV, Bakris GL, Black HR, et al.; National Heart, Lung, and Blood Institute Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure; National High Blood Pressure Education Program Coordinating Committee, The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report, JAMA, 2003;289:2560–72.
- PROGRESS Collaborative Group, Randomised trial of a perindopril-based blood-pressure-lowering regimen among 6,105 individuals with previous stroke or transient ischaemic attack, Lancet, 2001;358:1033–41.
- Lattimore SU, Chalela J, Davis L, et al., Impact of establishing a primary stroke center at a community hospital on the use of thrombolytic therapy: the NINDS Suburban Hospital Stroke Center experience, Stroke, 2003;34:e55–7.
- Alberts MJ, Hademenos G, Latchaw RE, et al.; Brain Attack Coalition, Recommendations for the establishment of primary stroke centers, JAMA, 2000;283:3102–9.
- Schwamm LH, Audebert HJ, Amarenco P, et al., Recommendations for the implementation of telemedicine within stroke systems of care: a policy statement from the American Heart Association, Stroke, 2009;40:2635–60.
- Levine SR, Gorman M, ‘Telestroke’: the application of telemedicine for stroke, Stroke, 1999;30:464–9.
- Audebert HJ, Schenkel J, Heuschmann PU, et al., Effects of the implementation of a telemedical stroke network: the Telemedic Pilot Project for Integrative Stroke Care (TEMPiS) in Bavaria, Germany, Lancet Neurol, 2006;5:742–8.