'Lousy' Prognosis for Incidentally Detected, Asymptomatic AF, but OACs Lower Risk

September 04, 2014

BARCELONA, SPAIN — Incidentally detected atrial fibrillation (AF) in asymptomatic and ambulatory patients is associated with a significantly increased risk of stroke, MI, and all-cause mortality, but treating the detected arrhythmia with oral anticoagulants can significantly improve the prognosis of these patients, according to the results of a new study.

The new data suggest that it would be worthwhile to initiate a communitywide screening program to detect and treat AF in these asymptomatic patients. Such a screening program would even be cost-effective, say researchers.

Dr Ben Freedman (Concord Hospital, University of Sydney, Australia) told heartwire that the prevalence of AF worldwide is only going to increase with the aging baby boomers. "This epidemic is looming," he said. "In the next 10 or 20 years, we're going to see this enormous increase in atrial fibrillation. It's going to be asymptomatic and silent."

And unfortunately, the first manifestation of AF can be devastating. "Often, in patients, the first time you learn they have atrial fibrillation is when they present with a stroke," said Freedman. In fact, he said that AF is responsible for 20% to 33% of all strokes and that 20% to 45% of individuals who have an AF-related stroke did not have a prior diagnosis of AF.

Freedman, along with colleagues Dr Carlos Martinez (Institute for Epidemiology, Statistics, and Informatics, Frankfurt, Germany) and Dr Nicole Lowres (University of Sydney), published the new data on the prognosis of incidentally detected ambulatory AF in the August 2014 issue of Thrombosis and Haemostasis[1] and also presented more research on the topic here at this week's European Society of Cardiology (ESC) 2014 Congress .

Communitywide Screening Not in Place

At present, the ESC guidelines recommend opportunistic screening for asymptomatic AF in patients >65 years. This can be done with pulse palpation or an ECG. The American Heart Association/American College of Cardiology/Heart Rhythm Society (AHA/ACC/HRS) update on AF does not advocate for such screening, stating only that "clinically unrecognized and asymptomatic AF is a potentially important cause of stroke," and this supports "efforts at early detection of AF in at-risk individuals."

In a systematic review published last year, Lowres along with Freedman reported that a single ECG or pulse check to screen for incidental ambulatory AF in those >65 years would detect 1.4% of individuals with AF both in the general population and clinic. Similarly, the researchers conducted a study known as SEARCH-AF , a study looking at the feasibility of using a novel iPhone ECG technology (AliveCor, San Francisco, CA) in community pharmacies and also found that the technology picked up asymptomatic AF in 1.5% of those screened.

"But people said, hang on, these people are asymptomatic," Freedman told heartwire . "Their heart rate is only 78 beats per minute. Is this really as bad as atrial fibrillation in patients who come to the hospital? The next part of the puzzle for us was to determine the prognosis of these patients."

To address how incidentally detected, ambulatory AF patients fared, Freedman teamed up with Martinez and analyzed data from the UK Clinical Practice Research Datalink, one of the largest primary-care databases in the world.

The analysis identified patients with a first diagnosis of atrial fibrillation and excluded any patients who were sent to the hospital for AF, those with symptoms for AF, or those who had a clinical event associated with AF. In the end, 5555 patients with asymptomatic AF were included, and their outcomes were compared with 24 705 age- and gender-matched controls. Patients were followed for a mean of 3.5 years.

Compared with the matched controls, there was a significant excess risk of stroke, MI, and all-cause mortality among individuals with silent AF. Regarding stroke, the incidence rate was 19.4 events per 1000 person-years among those with AF and 8.4 events per 1000 person-years among the controls. For all-cause mortality, the incidence rate was 40.1 deaths per 1000 person-years among the AF patients vs 20.9 per 1000 person-years in the control arm.

"They have a bad prognosis," said Freedman. "They have a doubling in their risk of stroke, a doubling in their risk of death, an increased risk of MI, and an increased risk of bleeding." This risk existed despite half of the patients receiving oral anticoagulants, he noted.

How Do They Respond to Treatment?

At the ESC, Freedman presented data on the response to oral-anticoagulant treatment in these incidentally detected, asymptomatic AF cases. Although it was not a randomized trial, he reported that the adjusted cumulative incidence of stroke at 18 months was just over 4% among the untreated AF patients, and this was reduced to almost 1% with oral anticoagulants but not by aspirin. All-cause mortality was reduced approximately from 7% to 4%, and the risk of fatal and nonfatal MI reduced approximately from 3% to 1.5% at 18 months. For stroke, the risk was reduced to the same level as the age- and gender-matched controls without AF.

In a multivariate-adjusted risk model, those who received a vitamin-K antagonist had a 65% lower risk of fatal and nonfatal stroke and a 44% lower risk of all-cause mortality compared with untreated incident AF individuals. Treatment with aspirin alone provided no benefit.

"That's another finding from this study," said Freedman. "Don't prescribe aspirin for this condition. It's not safe and it's not effective."

Given the prevalence of asymptomatic patients with AF, Freedman and his group are advocates for communitywide screening. They have tested various handheld ECG devices, often in community pharmacies, but have had the best success with the iPhone ECG screening tool. The technology allows a single lead ECG to be recorded on a standard iPhone when individuals place two fingers of each hand on the left and right electrodes on the back of the iPhone case. They published data on its sensitivity and specificity with an automated algorithm for detecting AF in 2013 in the International Journal of Cardiology and concluded the device would be ideal for community screening[2].

At the ESC meeting, Lowres presented cost-effectiveness data from the SEARCH-AF study using the iPhone to screen for AF[3]. Assuming the cost of the screen would be A$20 and that 55% of patients would be prescribed warfarin if AF were detected, she said the incremental cost-effectiveness ratio for extending the iPhone ECG screening tool into the community would be A$5988 per quality-adjusted life-year (QALY) gained and the cost of preventing one stroke would be A$30 481.

"So for me, we've sort of closed the loop," said Freedman. "We showed that incidentally detected asymptomatic atrial fibrillation is a common condition in people over 65. If you find it, it has a lousy prognosis. If you treat it, you can undo most of that lousy prognosis, but you've got to find it. And we found a really easy way of finding it, of diagnosing it, that's effective and cost-effective."

If just half of 65-year-olds were screened and only half of those prescribed oral anticoagulants, 123 strokes per year would be prevented in Australia, he added. If more were screened and anticoagulants used in more patients, between 200 and 300 strokes could be prevented each year, said Freedman. "This is something that has major health ramifications, in my view. I also believe that if we do this on a more widespread scale, we'll increase awareness of AF and increase adherence to prescriptions for oral anticoagulants."

Freedman reports research support and/or serving on advisory boards of Bayer, Sanofi, Boehringer-Ingelheim, Bristol-Myers Squibb, Servier, and AstraZeneca. Martinez reports grants, payment, and nonfinancial support from Bayer Pharma, payments from Boehringer Ingelheim, and grants and payments from CSL Behring. Lowres has reported no relevant financial relationships.

Editor's note: An original version of this story contained errors and misinterpreted the results. It was corrected and updated with new information from the ESC 2014 Congress.

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