LOOP and STROKESTOP: Impact of AF screening may influence arrhythmia burden

In older people at high risk for stroke, the benefits of screening for atrial fibrillation (AF) – and then treating it when it is detected – may depend on the types of episodes discovered, suggest results from the LOOP and STROKESTOP studies .

In the LOOP study, testing for AF with an implantable loop recorder (ILR) and then initiating anticoagulation for any episode lasting longer than 6 minutes did not significantly reduce the risk of stroke or systemic arterial embolism compared to standard care, Jesper Svendsen, MD (Copenhagen University Hospital – Rigshospitalet, Denmark), reported in a Hot Line session at the European Society of Cardiology (ESC) Virtual Congress 2021.

On the other hand, the results of STROKESTOP, published in the Lancet with LOOP but not part of the ESC program, show that screening individuals with ECGs twice daily for 2 weeks, then treating those with detected AF, led to a small but significant reduction in strokes ischemic / hemorrhagic, systemic embolism, bleeding resulting in hospitalization and death from all causes (HR 0.96; 95% CI 0.92-1.00; P = 0.045).

The difference is that the results between the two trials are likely related to the types of AF episodes detected using the respective screening approaches, according to Renate Schnabel, MD (University Heart & Vascular Center Hamburg, Germany), who said more frequent and longer TCTMD episodes are thought to be associated with a higher risk of stroke compared to less frequent and shorter episodes. ILR monitoring detected very short episodes in LOOP, while intermittent ECG screening in STROKESTOP likely identified individuals with more clinically significant AF, she said. “Now we need to rethink that not all atrial fibrillation is created equal. “

Indeed, the LOOP results in particular “could imply that not all atrial fibrillations are worth screening, and that not all atrial fibrillations detected by screening are worthy of anticoagulation,” write Svendsen et al in their report. article.

Taken together, Schnabel said, LOOP and STROKESTOP indicate “that screening for atrial fibrillation in those at risk – either by age or by enriched risk factors – may reduce stroke, systemic embolism and mortality, and can be profitable, if we find the right burden of atrial fibrillation that requires anticoagulation, ”said Schnabel.

The LOOP study

The idea behind population screening for AF is that many patients with arrhythmia have no symptoms, go undiagnosed, and therefore do not reap the benefits of oral anticoagulation for stroke prevention.

“European and American guidelines recommend opportunistic screening for atrial fibrillation in people aged 65 and over using pulse palpation or standard [ECG], while systematic or more intensive screening is recommended in people at high risk of stroke, ”note Svendsen et al. “These recommendations are based on studies showing that screening is feasible and will detect more cases of atrial fibrillation, while the effect on stroke prevention remains unknown.”

The LOOP study, carried out in four Danish centers, was designed to help answer this open question. Researchers recruited 6,004 patients aged 70 to 90 (mean age 74.7 years; 47.3% female) who had at least one of the following risk factors: hypertension, diabetes, heart failure or stroke. anterior cerebral. They were randomized 1: 3 for ILR monitoring – with Reveal LINQ (Medtronic) – or standard care, which involved an annual interview with a study nurse and typical interactions with the participant’s general practitioner. Most of the participants (90.7%) had hypertension, and the median CHA₂DS₂-The VASc score was 4.

As expected, with a median follow-up of 65 months, AF was more likely to be diagnosed in the ILR group (31.8% vs. 12.2%; P <0.001), for which the median duration of monitoring was 39.3 months. The initiation rate of oral anticoagulation was also higher (29.7% vs. 13.1%; P <0.0001).

However, this did not translate into a significantly lower rate of stroke or systemic arterial embolism with ILR monitoring compared to standard care (4.5% vs. 5.6%; HR 0.80; CI at 95% 0.61-1.05). A subgroup analysis suggested that screening reduced this endpoint in patients with the highest systolic blood pressure, but Svendsen stressed that the result only gives rise to speculation.

There were also no differences in all-cause deaths (11.2% vs. 11.3%; HR 1.00; 95% CI 0.84-1.19), deaths from CV (2.9% vs. 3.5%; HR 0.83; 95% CI 0.59-1.16) bleeding (4.3% vs. 3.5%; HR 1.26; 95% CI 0.95-1.69).

STOPPING THE RACE

The results of STROKESTOP were initially presented by Emma Svennberg, MD, PhD (Karolinska University Hospital Huddinge, Stockholm, Sweden), at the European Heart Rhythm Association Virtual Congress 2021 earlier this year. Residents aged 75 and 76 living in two regions of Sweden were randomized to be invited for screening, which consisted of intermittent ECG readings taken twice a day for 2 weeks, or not.

A total of 28,768 people were randomized and about half of those invited for screening (51.3%) actually participated.

The median follow-up in STROKESTOP — 6.9 years — was longer than the follow-up in the LOOP study. During this period, there was a slightly but significantly lower rate of the composite primary endpoint in the screening group (31.9% vs. 33.0%; P = 0.045).

These results “suggest that screening for atrial fibrillation in an older population has a net beneficial effect and should be considered part of health policy,” conclude Svennberg et al.

Time to strengthen the guidelines?

Discussing LOOP results after Svendsen’s presentation, Isabelle Van Gelder, MD, PhD (University Medical Center Groningen, The Netherlands), said the study helps fill some knowledge gaps regarding the population to be screened for, how do so and the importance of a low AF load.

She reviewed some possible explanations for the negative test result, including the detection of short subclinical episodes of AF; the use of a more restrictive primary endpoint compared to STROKESTOP; higher than expected AF detection rate in the control group; and the 12% early termination rate of ILR monitoring.

“The LOOP study contributes to the evidence that short episodes of subclinical AF are not worth screening for – lower stroke rate, no benefit from anticoagulation,” said Van Gelder. Together, she added, LOOP and STROKESTOP “suggest that atrial fibrillation detected by ECG in high-risk patients may more accurately identify those who benefit from anticoagulation due to clinical AF.”

But more studies on screening for AF are needed, she concluded.

For Schnabel, the results, in particular from STROKESTOP, confirm the current recommendations of the AF screening guidelines and may support their strengthening. The guidelines indicate that routine screening in people 75 years of age or older or with additional risk factors, such as in STROKESTOP, should be considered. “This will probably get an even stronger recommendation in the next guidelines,” Schnabel predicted.

What is important to stress, she added, is “that it is not only about the screening as it is done in these studies, but also as the STROKESTOP study shows. , there must be a platform for further examination, a reference, [and a] decision on oral anticoagulation to really implement effective screening policies. You probably don’t need intensive long-term monitoring. Intermittent monitoring may be sufficient, but screening for atrial fibrillation in individuals at risk should definitely be considered.

Additionally, screening programs need to step up efforts to reach people who are not participating, she said, noting that in STROKESTOP, those most at risk for adverse outcomes were those who were invited for screening but did not participate.