USPSTF Recommends Against Screening For Asymptomatic Carotid Artery Stenosis

Although stroke is a leading cause of death and disability in the United States, a relatively small proportion of all disabling strokes are due to Carotid Artery Stenosis (CAS).

The most commonly used screening test for severe CAS (60% to 99% stenosis) is duplex ultrasonography.  The accuracy of carotid duplex ultrasonography, by using digital subtraction angiography as the reference standard, estimate the sensitivity to be 86% to 90% and the specificity to be 87% to 94% for detecting CAS greater than 70%. The estimated sensitivity and specificity of carotid duplex ultrasonography to detect CAS of 60% or more are approximately 94% and 92%, respectively.  In 1996, the USPSTF reviewed the evidence for screening for bruits on physical examination and found that the test had poor reliability and poor sensitivity.  Good evidence indicates that duplex ultrasonography has moderate sensitivity and specificity but yields many false-positive results. A positive result on duplex ultrasonography is often confirmed by digital subtraction angiography, which is more accurate but is associated with complications. Given these facts, some people with a false-positive test results may receive unnecessary carotid endarterectomy surgery.

The evidence analyzed by the U.S. Preventive Services Task Force (USPSTF) indicates that in selected, high-risk trial participants with asymptomatic severe CAS, carotid endarterectomy by select surgeons reduces the 5-year absolute incidence of all strokes or peri-operative death by approximately 5%. These benefits would be less among asymptomatic people in the general population. For the general primary care population, the benefits are judged to be no greater than small.

Therefore evidence indicates that both the testing strategy and the treatment with carotid endarterectomy can cause harms. A testing strategy that includes angiography will itself cause some strokes. A testing strategy that does not include angiography will cause some strokes by leading to carotid endarterectomy in people who do not have severe CAS. In excellent centers, carotid endarterectomy is associated with a 30-day stroke or mortality rate of about 3%; some areas have higher rates. These harms are judged to be no less than small.

The U.S. Preventive Services Task Force concludes that for individuals with asymptomatic CAS there is moderate certainty that the benefits of screening do not outweigh the harms and its draft document gives a “D” recommendation.

Risk of Stroke due to Intracranial Atherosclerosis

Bos et al report in JAMA Neurology on the relationship between intracranial carotid artery calcifications and the risk of stroke in white populations.  As 80% to 90% of all strokes are due to acute ischemic strokes (AIS), it is important to recognize that atherosclerosis varies across the vascular beds and as such, different locations of vascular disease may have important role in AIS pathogenesis.  Atrial fibrillation and large-artery atherosclerosis such as in aortic arch and extra-cranial carotids are recognized as a major risk factors for AIS.  How common strokes occur after occlusion of the small intra-cerebral arteries, in so-called cerebral small-vessel disease is not well understood.

Between the years 2003 and 2006, a random sample of 2323 stroke-free persons (mean age, 69.5 years) underwent computed tomography scanning to quantify intracranial carotid artery calcification burden.  The population-based cohort was from the general community and part of the Rotterdam Study. All participants were continuously monitored for the occurrence of stroke until January 1, 2012.

During 14 055 person-years of follow-up, 91 participants had a stroke, of which 74 were acute ischemic strokes.  Large intracranial carotid artery calcification burden was related to a higher risk of stroke, independent of cardiovascular risk factors, ultrasound carotid plaque score, and calcification in other vessels.  Intracranial carotid artery calcification contributed to 75% of all strokes; for aortic arch and extra-cranial carotid artery calcification this incidence was only 45% and 25%, respectively.  As the sum of risk factors for strokes exceeds 100%, it suggests interaction between them as well as that unknown causes may contribute to AIS.

The findings of their study establish intracranial atherosclerosis as a major risk factor for stroke in the general white population and suggest that its contribution to the number of all acute ischemic strokes may be greater than atherosclerosis in common and internal carotid arteries as well as that from the arch of the aorta.

Efficiencies Result in Better Outcomes in Patients with Strokes

Despite two decades of efforts to initiate therapy of patients with acute ischemic strokes (AIS) quickly, less than one-third of patients presenting with AIS in the United States, were treated within the guideline-recommended door-to-needle (DTN) time with tissue plasminogen activator (tPA).  Fonarow et al¹ article in JAMA discusses strategies that were implemented in a consortium of hospitals in order to reduce DTN time to 60 minutes or less for the initiation of thrombolysis with tPA in patients with acute ischemic strokes.

The Stroke initiative made recommendations to 1030 participating hospitals that treated 71 169 patients with AIS with tPA (27 319 during the pre-intervention period and 43 850 during the post-intervention period).  The quality stroke initiative included pre-notification of hospitals by emergency medical services (EMS), fast performance and interpretation of brain CT scans, immediate initiation of treatment for eligible patients, rapid feedback on performance and public recognition of high-performing hospitals.

Median DTN time for tPA administration declined from 77 minutes during the pre-intervention period to 67 minutes during the post-intervention period (P < .001). The DTN times for tPA administration of 60 minutes or less increased from 26.5% of patients during the pre-intervention period to 41.3% during the post-intervention period (P < .001). The annual rate of improvement in DTN times of 60 minutes or less increased from 1.36% per year pre-intervention to 6.20% per year post-intervention (P < .001). In-hospital all-cause mortality improved significantly from the pre-intervention to the post-intervention period from 9.93% to 8.25%, respectively (P < .001), symptomatic intracranial hemorrhage within 36 hours decreased from 5.68% to 4.68% (P < .001), and discharge to home was more frequent from 37.6% to 42.7% (P < .001).

Prior studies² have established that thrombolysis with tPA is effective when administered early with the goal being to initiate treatment within 60 minutes or less from the time patients arrive in the hospital.  The authors report that their initiative was associated with improved timeliness of thrombolysis following acute ischemic stroke on a national scale, and that this improvement was associated with lower in-hospital mortality and intracranial hemorrhage, along with an increase in the percentage of patients discharged home.

1.  Fonarow G, Zhao X, Smith E, Saver J et al. Door-to-Needle Times for Tissue Plasminogen Activator Administration and Clinical Outcomes in Acute Ischemic Stroke Before and After a Quality Improvement Initiative; JAMA. 2014;311(16):1632-1640.    doi:10.1001/jama.2014.3203.

2.  Hacke W, Donnan G, Fieschi C, Kaste M et al, Association of outcome with early stroke treatment: pooled analysis of ATLANTIS, ECASS, and NINDS rt-PA stroke trials. Lancet 2004 Mar 6; 363(9411): 768-74.

Ambulance-Based Thrombolysis in Acute Ischemic Stroke

Ebinger et al report in JAMA the result a specialized ambulance has in the initiation of treatment in patients with acute ischemic strokes.

Their study was conducted in Berlin, Germany over a 21 months period between 2011 and 2013 when a Stroke Emergency Mobile (STEMO) unit was dispatched every other week to care of patients with strokes. The STEMO was an ambulance equipped with a CT scanner, point-of-care laboratory, with telemedicine connection, a physician, a paramedic and an x-ray technician. Thrombolysis was started before transport to hospital if ischemic stroke was confirmed and contraindications excluded.  During the study period 6182 adult patients were included.

There was a reduction of 25-minutes in alarm-to-treatment times for STEMO compared to control weeks.  The 25-minute reduction was due to faster alarm-to-imaging and imaging-to-treatment intervals. Fifty eight percent of patients were treated within 90 minutes of onset versus 37% in the control.  The intervention also resulted in 33% patients treated with tPA versus 21% in the control.  STEMO deployment incurred no increased risk for intra-cerebral hemorrhage (7/200 vs 22/323); or 7-day mortality (9/199 versus 15/323).

A prior study by Walter et al¹ who also used a mobile stroke unit and treated patients with acute ischemic stroke with tPA safely within 70 to 80 minutes.

The authors conclude the use of ambulance-based thrombolysis resulted in decreased time to treatment without an increase in adverse events. 

1.  Walter S, Kostopoulos P,  Haass A et al. Diagnosis and treatment of patients with stroke in a mobile unit versus hospital: a randomized study controlled trial Lancet Neurol. 2012;11(5):397-404