USPSTF Finds Insufficient Evidence for AF Screening

August 07, 2018

A final statement from the US Preventive Services Task Force (USPSTF) concludes that there is insufficient evidence to determine the balance of benefits and harms of screening for atrial fibrillation (AF) with electrocardiography (ECG) in asymptomatic adults. "Evidence is lacking, and the balance of benefits and harms cannot be determined," it says.

The recommendation comes after the Task Force undertook a detailed review of the evidence on screening for previously undiagnosed AF and the benefits and harms of stroke prevention treatment in populations and settings relevant to US primary care.

Their findings are reported in a paper published online in JAMA on August 7, together with a separate recommendation statement.

The Task Force published its very similar draft recommendations on the issue in December 2017. 

"Although screening with ECG can detect previously unknown cases of atrial fibrillation, it has not been shown to detect more cases than screening focused on pulse palpation," the Task Force states. "Treatments for AF reduce the risk of stroke and all-cause mortality and increase the risk of bleeding, but trials have not assessed whether treatment of screen-detected asymptomatic older adults results in better health outcomes than treatment after detection by usual care or after symptoms develop."

The Task Force notes that AF increases the risk for stroke and thromboembolism by reducing cardiac blood flow and predisposing to thrombus formation, particularly in the left atrial appendage. For persons with AF, the annual incidence of stroke increases by about 1.5% per decade, from 1.3% in those aged 50 to 59 years to 5.1% in those aged 80 to 89 years. 

Further, strokes attributable to AF are associated with a poor prognosis: Approximately 30% of patients die within 1 year of the stroke, and up to 30% of survivors are left permanently disabled.

Of patients who have a stroke attributable to AF, an estimated 20% or more are diagnosed with AF only at the time of the stroke or shortly thereafter. The current review therefore examined the evidence as to whether identifying asymptomatic AF and starting anticoagulation therapy may prevent strokes and deaths.

The Task Force reviewed 17 studies in a total of 135,300 individuals. None of these studies evaluated the effect of screening vs no screening on health outcomes.

The studies did show that systematic screening with ECG identified more new cases of AF than no screening (absolute increase from 0.6% to 2.8% over 12 months). However, a systematic approach using ECG did not detect more cases than did an approach using pulse palpation.

For potential harms, no eligible studies compared screening with no screening.

Warfarin (mean, 1.5 years) was associated with a reduced risk for ischemic stroke (relative risk, 0.32) and all-cause mortality (relative risk, 0.68) and with increased risk for bleeding, but patients in treatment trials were not screen detected, and most had long-standing persistent AF.

A network meta-analysis reported that novel oral anticoagulants were associated with a significantly lower risk for a composite outcome of stroke and systemic embolism (odds ratio, 0.32 - 0.44), and an increased risk for bleeding (odds ratio, 1.4 - 2.2), but confidence intervals were wide and differences between groups were not statistically significant.

The Task Force review and recommendations are also the subject of three editorials in different JAMA publications.

Effective AF Screening: A Public Health Priority

In the main JAMA journal, Jeffrey J. Goldberger, MD, and Raul D. Mitrani, MD, University of Miami Miller School of Medicine, Florida, say in their editorial that the development of an effective screening strategy for prevention of AF-associated cardioembolic stroke should be a public health priority, but this may involve other strategies beyond ECG screening.

To Medscape Medical News, Goldberger pointed out that ongoing studies are looking at whether AF screening prevents strokes, "but even if they are positive, which I hope they are, I believe we will still have to move beyond AF for stroke risk factor detection," he said. "The trouble with ECG screening is that a 10-second snapshot is not very helpful to pick up AF — that's worse that a needle in a haystack. We need inexpensive long-term monitoring. I suspect smart-watch apps will be the future." 

He pointed out that screening for atrial disease may be a more effective option altogether. "We used to believe that AF caused stroke, but we are leaning now that actually it is atrial disease that predisposes to blood clots that lead to stroke," he said. 

Atrial disease can also lead to AF, but it not necessarily a linear process of atrial disease leading to AF leading to stroke, he added. "Sometime AF can occur after the stroke or it may not occur at all. It is therefore better to detect atrial disease itself, and studies are now ongoing in patients who have had a cryptogenic stroke looking at other markers of atrial disease."

On the current recommendation. Goldberger said he thinks it is hard to be dogmatic. 

"Clearly if you find a pulse irregularity then, yes, you will want to do an ECG. Beyond that, the task force is right — there isn't enough data for a clear recommendation for mass screening. But I think we can make individual decisions on a case-by-case basis. If a patient has several risk factors for stroke, then I think it is justifiable to ask for an ECG.

"The kind of strategy of who to screen and how to screen is very much open to discussion," he added. "But I don't think we should abandon the whole notion of screening for a major factor for one of the most debilitating conditions. People complain about ECG screening being expensive but having a stroke is extremely expensive to society."

In an editorial in JAMA Cardiology, Rod Passman, MD, and Jonathan Piccini, MD, note that the European Society of Cardiology (ESC) and American Heart Association recommend opportunistic AF screening for successful stroke prevention with pulse palpation, followed by ECG only if results of the physical examination are abnormal. 

The USPSTF additionally notes in their recommendation statement that the ESC recommends considering systematic screening to detect AF in persons older than 75 years or those at high risk for stroke.

Commenting for Medscape Medical News, Passman said he agrees with the opportunistic approach. "Routine ECG screening to look for AF is clearly not cost-effective," he said. "It doesn't find more than opportunistic screening in patients who have irregular pulse or heart sounds picked up on physical exam. The current USPSTF paper reinforces that view."

He advises that patients who have two or more stroke risk factors, such as age and blood pressure, diabetes, and vascular disease, should undergo regular physical exams and pulse checks at routine office visits and then be referred for ECG if irregularities are found at the physical exam.

"However, as AF is a very strong risk factor for stroke — and we know anticoagulation reduces this risk — I do think we should be considering widespread screening programs for the whole population at a certain age using just a physical exam/pulse check in the first instance. That would be a lot cheaper than ECG screening."

But Passman pointed out that because of the intermittent nature of much AF, many cases would still be missed. "We have to ask how can we leverage new technology to screen people over the long term. Implantable devices are very expensive, but I think smart phones or watches are the way forward," he said. "There are already apps available for AF screening and in future I think we will be training our patients to screen themselves in this way."

Number Needed to Screen to Prevent One Stroke: 10,000?

In another editorial, this time in JAMA Internal Medicine, John Mandrola, MD, Baptist Health Louisville, Kentucky, and  Andrew Foy, MD, and Gerald Naccarelli, MD, Penn State University College of Medicine, Hershey, Pennsylvania, drum home the inefficacy of AF screening by analyzing data from the STROKESTOP study of intermittent ECG recordings among individuals aged 75 to 76 years in Sweden. They calculate that the number needed to screen to prevent one stroke equals 10,000.

For comparison, they say the number needed to screen for abdominal aortic aneurysm to save one disease-specific death is 250, and for fecal occult blood testing screening it is 625.8.

"A cost analysis is sobering," they write. "If an ECG costs $100, society would pay $1 million (100 × 10 000 NNS [number needed to screen]) to prevent 1 stroke in persons older than 75 years, and even more in younger persons."

In response to these calculations, Goldberger said he thinks these numbers are "overly pessimistic" and that Mandrola et al have underestimated the risk reduction from anticoagulation and only looked at a 1-year time frame.

He gave a different estimate for the calculation using a 1-year risk for stroke in patients not anticoagulated of 4.5%, and an 80% relative reduction in stroke with anticoagulation that extended over 5 years he said would reduce the number needed to screen to 1250 people to prevent one stroke.

"If we had better tools to identify which patients with AF need anticoagulation, the benefit of anticoagulation would be larger and the number needed to screen would go down further," he added.

To Medscape Medical News, Mandrola said he "strongly agrees" with the Task Force recommendation.

"I think it is unlikely that mass screening or even focused screening will deliver reduced outcomes for many reasons," he said. "ECG screening picks up very few cases of AF and we don't know whether the AF picked up by screening is harmful or not. We don't know what a 2-minute period of AF means. The trials of anticoagulants were done in the 1990s in patients referred with AF. That is different to AF identified by screening the whole population."

Then there is the issue of misdiagnosis, he said. "AF has a low incidence in the whole population, many people will be misdiagnosed and subjected to a cascade of different tests which will have complications, as well as the bleeding side effects of anticoagulant use, and of course the costs will be enormous."

Mandrola said he can't argue against doing ECG in those with an irregular pulse. "Yes sure, if someone is aged 75 and has high blood pressure and an irregular pulse then an ECG should be certainly be done, but that's not screening." 

On longer-term methods of screening, Mandrola said these may offer a more effective way of detecting AF but it is unknown whether this will translate into reduced stroke outcomes. 

"The recent mSToPS study using a patch worn for 2 weeks to screen for AF picked up a small amount of short duration AF," he pointed out. "That showed that if you look for AF you will find it and this leads to an increase in the use of anticoagulants and an increase in spending on resources, but it's not clear that this will result in a reduction in outcomes," he added.

"We don't have that data. We are saying that we don't think this is a sure win. We need evidence of benefit before recommending mass screening or even focused screening, so the way forward is systematic pragmatic studies."

Lead author of the mSToPS study, Steven R. Steinhubl, MD, Scripps Translational Science Institute in La Jolla, California, responded to Medscape Medical News that: "Additional follow-up in mSToPS will provide much better data around the consequences of ECG screening in terms of additional healthcare utilization, as well as whether screening and detecting AF improves outcomes." 

He also noted out that further follow-up of the STROKE STOP study should be available later this year and may help answer the value of AF screening in terms of stroke prevention.

Steinhubl pointed out that a recent analysis of claims data in relatively young people (average age < 63 years) found that of people with AF and a stroke that for over half their AF was not diagnosed until they had a stroke. "I believe we can significantly impact that with proper screening programs."

He added: "I believe we need to start thinking of AF discovered by screening to be considered a risk marker that should drive more aggressive preventative therapies, not just anticoagulation. Studies have shown that interventions such as weight loss, treatment of sleep apnea, and therapies for hypertension and diabetes can impact AF risk. There is still much to learn about what exactly is best for individuals with newly diagnosed AF and that data is forthcoming. I hope and believe that data available in the near future will make today's USPSTF recommendations out-of-date very rapidly."

JAMA. Published online August 7, 2018.  Recommendation statement, Evidence report, Editorial

JAMA Cardiol.  Published online August 7, 2018. Editorial

JAMA Intern Med. Published online August 7, 2018. Editorial

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