Aggressive screening for undiagnosed AF beneficial, but only in those most at risk
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More aggressive monitoring for undiagnosed atrial fibrillation may be beneficial in preventing future hospitalization, but the benefit may be limited to higher-risk patients, according to results from the VITAL-AF and mSToPS trials.
Presented at the virtual American Heart Association Scientific Sessions, these two trials evaluated point-of-care and active ECG monitoring methods for the detection of undiagnosed AF and evaluated their impact on guideline anticoagulation use and longer-term outcomes.
VITAL-AF
In VITAL-AF, investigators enrolled 30,722 patients (mean age, 74 years; 59% women; 83% white) from 16 practices within the Massachusetts General Hospital network to determine whether point-of-care rhythm assessment with a single-lead ECG (AliveCor) may increase newly diagnosed AF compared with a control group who received diagnosis at a follow-up visit.
“VITAL-AF examined the potential for patients with most likely persistent forms of AF to be diagnosed at the time of a primary care practice encounter using a point-of-care screen,” Steven A. Lubitz, MD, MPH, associate professor at Harvard Medical School and cardiac electrophysiologist at Massachusetts General Hospital, told Healio. “Other studies examining ambulatory or continuous rhythm monitoring or short-term repeated forms of monitoring are likely addressing a different question about paroxysmal forms of AF, for which we have less understanding of the potential risks of ischemic stroke.”
Overall, 3% of screened encounters in the primary care setting were identified as having possible AF, 12% were unclassified and 83% were normal; there was no analysis for the remaining 2%. Of those with possible AF, approximately 50% were accompanied by a same-day 12-lead ECG, compared with less than 10% of patients with an unclassified or normal screen.
Compared with individuals who were not screened in the point-of-care setting, single-lead ECG did not significantly affect new diagnosis of new AF in the overall population of the VITAL-AF trial (new diagnosis, 1.74% of screening group vs. 1.6% of control arm; P = .33). The incidence rate of new AF diagnosis per 100 person-years in the screening group was 2.59 compared with 2.35 in the control group (P = .27).
However, the association between point-of-care screening and new AF diagnosis was stronger among patients aged 85 years or older, with a risk difference of 1.88% (95% CI, 0.27-3.35) and a number needed to screen of 53 (95% CI, 30-337) compared with the control arm.
After analyzing the proportion of newly diagnosed AF in primary care encounters and the total number of event encounters, investigators determined that the likelihood of AF diagnosis in the primary care setting may be greater with single-lead ECG screening (100 events in 38,374 encounters) compared with the control group (72 events in 40,003 encounters; P = .02).
“VITAL-AF puts in perspective a strategy that has been endorsed in some, but not all, guidelines and that is that opportunistic screening at the time of a clinic encounter may be effective for identifying undiagnosed AF,” Lubitz said in an interview. “We know that if you look for AF, you can find AF, but one of the questions is what is the most efficient way for identifying AF that’s undiagnosed [but] high-risk enough to cause a potential stroke, and that remains an unanswered question.”
In a secondary analysis, researchers observed that although the rate of new anticoagulation initiation declined with increasing patient age, there was no significant difference between the intervention and control arms (P = .61).
“VITAL-AF definitively answers, in a contemporary U.S. practice like ours, the question of what the potential effect is of screening for AF using single-lead ECG,” Lubitz told Healio. “These results should help put in context existing recommendations for screening and identify new areas for future research.”
mSToPS
The second trial was a secondary analysis of the mSToPS study, in which investigators sought to determine whether AF screening via an ECG monitor (Zio patch, iRhythm Technologies) can improve clinical outcomes at 3 years after initiation of screening (mean age, 74 years; 41% women; median CHA2DS2 score, 3). The primary composite outcome was time to death or first stroke, systemic embolism or MI among participants with a diagnosis of AF at any time during the 3-year analysis and among the entire cohort at 3 years. The primary safety endpoint was incidence of hospitalization for bleeding.
As Healio previously reported at the 2018 American College of Cardiology Scientific Session, an ECG patch conferred improved diagnosis of AF, use of guideline-recommended therapies and increased health care utilization.
“The mSToPS trial was a unique, direct-to-participant, siteless design carried out within the Aetna health payer system and was primarily digital outreach recruitment and enrollment,” Steven R. Steinhubl, MD, director of digital medicine at Scripps Translational Science Institute and a cardiologist at Scripps Health, said during his presentation. “Individuals who agreed to participate were sent a Zio patch, which they placed on themselves and the results from the Zio patch were sent back to the participant, and if they agreed, were sent to their physician. No guidance was provided to the physicians as to what to do with the results. Just an explanation of the trial and a brief evaluation of what was found overall.”
Overall, 11.4% of actively monitored patients were diagnosed with AF compared with 7.7% of the matched control group (P < .01). However, 68% of AF diagnoses in the ECG patch group were attributed a clinical diagnosis, not active monitoring.
Anticoagulants were initiated in approximately 44% of the actively monitored cohort and 45.2% of matched controls (P = .84).
Investigators found that participants in the ECG patch group experienced fewer events (4.5 per 100 person-years) compared with the control arm (5.5 per 100 person-years; adjusted HR = 0.79; P < .01).
The association was stronger when researchers looked at only those who received a diagnosis of AF during the 3-year study period, with 8.4 events per 100 person-years in the actively monitored group and 13.8 events per 100 person-years in the control arm (aHR = 0.53; P < .01).
In addition, patients in the actively monitored group who received their AF diagnosis via ECG patch first experienced fewer occurrences of the composite endpoint (2.6 events per 100 person-years) compared with those who were actively monitored and diagnosed clinically and the control group (P for both < .01).
Moreover, incidence of the composite outcome among participants in the ECG patch group who were diagnosed clinically was not significantly different compared with the control group (10.9 vs. 13.8 events per 100 person-years; P = .21).
“When outcomes for the AF diagnosis subset are broken down by the mode of diagnosis, as expected, there is no difference between those who are clinically diagnosed, as their pathway in health care and diagnosis will be similar. It is only those diagnosed with ECG patch that experienced significantly better outcomes,” Steinhubl said during the presentation. “It is important to highlight that these analyses are likely confounded by spectrum bias, and it therefore is being shown purely for mechanistic consideration only.”
For the safety endpoint, patients who were actively monitored had a lower incident rate for total hospitalizations (adjusted incident rate [IR] = 0.69; 95% CI, 0.63-0.76; P < .01) and hospitalizations for bleeding (aIR = 0.47; 95% CI, 0.26-0.85; P = .01).
“We need to keep several limitations in mind. Foremost, the comparison between individuals choosing to participate in a randomized trial, making up a low single-digit percentage of individuals who received an invitation, and the observational cohort, may be biased by unmeasured confounding, despite adjusting for all comorbidities and baseline health care utilization,” Steinhubl said.
“Active screening for AF as part of a pragmatic direct-to-participant nationwide study was associated with significant improvement in clinical outcomes and safety at 3 years relative to routine care,” Steinhubl said during the presentation. “However, independent replication that these results are required in order to be confident that aggressive pursuit of diagnosing atrial fibrillation and people at high risk but without symptoms is warranted.”
Reference:
- Steinhubl SR, et al. LBS.06: To screen or not to screen, and then what? Studies of detection and treatment of AF. Presented at: American Heart Association Scientific Sessions; Nov. 13-17, 2020 (virtual meeting).
Perspective
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Annabelle Santos Volgman, MD, FACC, FAHA
Preventing strokes is the ultimate reason to carry out screening for AF. We strive to lower our patients’ BP and cholesterol and control their diabetes to prevent strokes. Despite these efforts, there are patients who still suffer from strokes. It is devastating when we find out that they had asymptomatic AF. This scenario haunts any clinician. The international effort to discover occult AF to prevent strokes became much more possible with the approval of the non-vitamin K anticoagulants and cost-effective technology to detect AF.
We awaited trials to inform us on whether we should encourage our patients to buy monitors to discover that elusive AF. VITAL-AF investigators studied more than 35,000 patients in a primary care setting with no history of AF to determine if point-of-care single-lead rhythm determination would identify patients with occult AF. The study found that actively screening for AF was only effective in patients older than 85 years. The usual care was as good as active screening in younger patients. VITAL-AF will continue to try to answer two more questions: What is the adherence to anticoagulation, and whether stroke prevention outweighs the risk for bleeding.
The mSToPS trial gave us a glimpse of the answers to those two questions. It is a study by an insurance company to determine if screening for AF using an ECG patch can improve clinical outcomes at 3 years after the initiation of screening. The study found that the patch increased the diagnosis of AF and about 45% of the patients were anticoagulated. After 3 years, the study found that there is significant improvement in deaths in the actively monitored group but no difference in strokes or other endpoints, compared to the control group. There were also less hospitalizations and bleeding in the monitored group.
The study proved that screening for AF can detect AF and the monitored patients had less deaths and hospitalizations and bleeding compared with the control group. This tells us that monitored patients do better since they are more closely followed, but it does not demonstrate that strokes can be prevented by screening for AF. We await other studies to shed light on whether screening for AF can decrease strokes.
Perspective
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Jim W. Cheung, MD, FACC
In the VITAL-AF trial, investigators examined the effectiveness of single-lead ECG screening in a primary care setting to diagnose AF. This large study enrolled over 35,000 patients, and interestingly, the researchers found no significant differences in new AF diagnoses between the screening group and the control group. It was only in the subgroup of patients aged 85 years or older did screening identify an increased proportion of patients with AF.
This study might dampen some of the enthusiasm for widespread screening of patients for AF in the absence of assessing for risk factors such as advanced age and other comorbidities. These findings may lead to questions about the role for other wearable technologies for AF screening, as many of these devices are typically worn by younger patients who are at even lower baseline risk for AF than patients in the VITAL-AF trial. The proper strategy for AF screening will need to be refined to yield meaningful increases in new AF diagnoses.
In the mSToPS trial, the researchers conducted a pragmatic direct-to-participant study and found that patients who enrolled in active monitoring with an ECG patch had a significant reduction in the primary endpoint of combined death, stroke, myocardial infarction and systemic embolism when compared with a matched cohort of patients who did not undergo active monitoring. This is a provocative study, as it points to an association between enrollment in active monitoring for AF and improved outcomes.
However, there are several limitations that should be considered. First, in the active monitoring arm, only 32% of them had their AF detected by the ECG while 68% received the AF diagnosis on a clinical basis. Second, among the patients for whom pharmacy data were available, only a minority of patients who had an AF diagnosis were actually on anticoagulation. This raises questions about whether the improvement in outcomes associated with active monitoring could, in fact, be attributed to anticoagulation intervention. Finally, it should be noted that patients who consent to a study involving active monitoring are more likely to be patients who are more apt to follow-up with physicians, to be compliant with medications, and to engage the health care system in an active manner. Such patients are likely to have unadjusted confounders that are associated with improved health outcomes. Previously published observational studies showing improved outcomes among patients undergoing remote monitoring of cardiac implantable electronic devices have similar limitations. Despite these limitations, the mSToPS trial is an important study, as it introduces a blueprint for future pragmatic studies examining the impact of AF screening in large populations.
The researchers behind both the VITAL-AF and mSToPS trials should be commended for undertaking large studies that examine the utility of AF screening in a clinically relevant way. The findings from these two studies chart a path for refining strategies for meaningful AF screening to improve outcomes.
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Lubitz SA, et al. LBS.06: To screen or not to screen, and then what? Studies of detection and treatment of AF. Presented at: American Heart Association Scientific Sessions; Nov. 13-17, 2020 (virtual meeting).
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