Modest clinical gain in an asymptomatic AF screening trial

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Some, perhaps many, previously unrecognized cases of atrial fibrillation (AF) will come to light in a screening program aimed at older asymptomatic adults. The key question is whether the challenges of this systematic but age-restricted AF screening in the community, with oral anticoagulation (OAC) to those with arrhythmia, are worth preventing events such as death or stroke.

There is now evidence to support this clinical benefit of a large prospective, randomized trial. A screening program restricted to people aged 75 or 76 in two Swedish communities, which required them to use a single hand driver ECG system at home intermittently for 2 weeks, was followed by a slight drop in clinical events for about 7 years.

4% risk reduction (Pg = .045) in the file STROKESTOP the “intention to treat” (ITT) analysis of the trial gave a number needed to treat 91; that is, many people had to be targets of the screening program to prevent a clinical event of primary purpose.

Included ischemic stroke, systemic thromboembolism, hospitalization for severe bleeding and death from any cause, the researchers reported on April 23 during the 2021 virtual congress of the European Heart Rate Association (EHRA).

If this benefit and its importance seem marginal, some secondary findings may be reassuring. Half of the target age population of the two communities (13,979 randomly selected people) were invited to join the trial and follow the selection protocol, which comprises the ITT cohort. The other half, with 13,996, was not invited and served as control subjects.

However, only 51% of the ITT cohort accepted the invitation and participated in the trial; they represented the cohort “as it was treated,” observed Emma Svennberg, MD, PhD, Karolinska Institute, Danderyd Hospital, Stockholm, who presented the analysis at EHRA sessions.

The screening protocol identified untreated AF, whether known or unknown previously, in approximately 5% of the 7165 screening participants treated; OAC was initiated in approximately three-quarters of these cases.

The treated group, by itself, benefited from a 24% drop in the defined secondary endpoint of ischemic stroke prospectively, compared with the entire control group.

The clinical benefit in the ITT population was “small but significant,” but during the same period of the treated cohort there was a very significant drop in the risk of ischemic stroke, Svennberg said. theheart.org | Cardiology Medscape.

According to her, the main message of the trial is that “the detection of atrial fibrillation in an elderly population reduces the risk of death and ischemic stroke without increasing the risk of bleeding.”

Warnings: As-Treated vs ITT

But there are warnings that complicate the interpretation of the judgment and, Svennberg proposed, point to the importance of this interpretation of both the ITT and the analyzes discussed.

“We detected significantly more atrial fibrillation in the randomized screening group. One of the strengths of our study was that we referred all of these people for structured follow-up within the study, “he said.” Although follow-up focused on oral anticoagulant therapy, other risk factors were also assessed and managed, such as hypertension and diabetes “.

It is possible that increased AF detection followed by this structured management contributed to the observed benefit, Svennberg proposed.

However, the exclusion of those from the pre-specified ITT population who refused to be examined or did not participate in any other way left a cohort treated healthier than the ITT population or the control group.

In fact, non-participating guests were sicker, with significantly more diabetes, vascular disease, hypertension, and heart attack, and upper CHA2DS2VASc stroke risk scores than those who agreed to participate.

“We took a more difficult route in setting up this study, as we identified all people aged 75 to 76 who resided in our two regions and did not exclude anyone,” Svennberg said in an interview. “This means that even people with end-stage disease, severe dementia, hiding in bed in residences, etc. were also randomized, but may not be likely to participate.”

Therefore, some guests were unable to join the study, although others may have declined “out of little interest” or for other personal reasons, he said. “We believe this mimics how a population-based screening program would be conducted if done in our country.”

In the ITT analysis, screening successfully identified cases of unknown or untreated AF previously, which led to increased use of OAC and intensification of risk factor management, “which was key to a successful outcome “.

In the analysis as it was treated, Svennberg said, “I think a combination of the intervention and that the population as a whole was healthier led to the secondary endpoint.”

Systematic vs. opportunistic projection

While current recommendations from the European Society of Cardiology recommend “opportunistic screening in people 65 and older,” systematic screening, such as that used at STROKESTOP, has a much weaker evidence base, he said. observe Renate B. Schnabel, MD, PhD, University Heart & Vascular Center, Hamburg, Germany, as a guest speaker after the STROKESTOP presentation.

STROKESTOP “is one of the first, if not the first, studies that demonstrates a clinical benefit derived from AF screening, Schnabel said.

During the trial fewer primary outcome events were seen than projected and the event curves for controlled and controlled participants did not begin to separate until about 4 years into the study, he said. Therefore, it may take a long time for selected seniors to realize the clinical benefits of screening.

Studies like the recent one SCREEN-AF i mSTOPS have widely demonstrated that screening for AF in asymptomatic elderly people can reveal hitherto unrecognized AF much more frequently than would be detected in routine practice, allowing them the opportunity to go to OAC. But the trials were unable to demonstrate whether the benefits of this management outweigh the risks or costs.

In fact, on April 20, the U.S. Prevention Services Working Group (USPSTF) released a draft statement of recommendation concluding that “the current evidence is insufficient to assess the balance of benefits and harms” associated with AF screening in asymptomatic individuals at least 50 years of age.

However, at STROKESTOP, the benefit for the primary outcome reached prominence in the pre-specified ITT analysis and “appeared to be driven by the reduction in the incidence of ischemic stroke,” Schnabel said.

“Future guidelines have yielded solid evidence to judge on the systematic screening of atrial fibrillation” as carried out during the trial, he said. “How to implement atrial fibrillation screening, including systematic screening in healthcare systems across Europe and beyond, remains an open question.”

A random population

STROKESTOP considered all children aged 75 and 76 living in the Swedish county of Stockholm (n = 23,888) and the Halland region (n = 4,880) and randomly assigned them to the ITT group or a control group, with stratification for sex, year of birth, and geographic region. In both groups, 54.6% were women and the average CHA2DS2The VASc score was 3.5.

People assigned to the ITT cohort were invited to be examined and followed up. Those who agreed to participate were subjected to an ECG-based evaluation to detect or rule out permanent AF. OAC and guideline-based follow-up were offered to those who encountered arrhythmia. Those with a sinus rhythm with no history of AF used a monofuel ECG handheld recorder (Zenicor) for 30 seconds twice a day for 14 days.

Structured management, including the OAC, was offered to anyone who demonstrated sufficient AF, i.e., at least one p-wave combat in a 30-second recording or at least two such episodes of 10 at 29 seconds during the 2-week projection period.

In the ITT analysis, the hazard ratio (FC) for the final compound clinical value was 0.96 (95% CI, 0.920 – 0.999; Pg = 0.045), but in the treatment analysis, the HR of ischemic stroke was 0.76 (95% CI: 0.68 – 0.87; Pg <.001).

“I think this will probably be generalizable to older people in most countries,” Svennberg said. “I think if we can find a significant difference in our large population in Sweden, most countries will be able to do it or find even more significant results.”

This is because “basal detection of FA in Sweden is high,” he said, “so new detection is likely to be more difficult.” Also in Sweden, “care can be requested without monetary worries and low-cost prescriptions are provided for patients.” Therefore, patients recently identified with AF, whether in studies or not, “would probably begin therapy.”

It will be important to know if the selection strategy is cost-effective, Schnabel said, because “the overall effect, with a risk ratio of 0.96, is not too great and the costs of systematic screening are comparatively high.”

STROKESTOP “now provides solid information for cost-effectiveness analysis, which has so far been largely based on assumptions.”

STROKESTOP received partial support from Carl Bennet AB, Boehringer-Ingelheim, Bayer, Bristol-Meyers Squibb and Pfizer. Svennberg reveals receipt of fees for conferences or consultations from Bayer, Bristol-Meyers Squibb, Pfizer, Boehringer-Ingelheim, Merck Sharp & Dohme and Sanofi; and institutional grants from Roche Diagnostics and Carl Bennett Ltd.

Congress of the European Heart Rate Association (EHRA) 2021. Late rupture clinical trials. Filed on April 23, 2021.

Follow Steve Stiles on Twitter: @ SteveStiles2. For more information at theheart.org | Medscape Cardiology, follow us Twitter i Facebook.





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