Early rhythm control for AF beneficial for older patients with high comorbidity burden
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In patients with recently diagnosed atrial fibrillation and a high comorbidity burden, early rhythm control therapy markedly reduced CV death, stroke or hospitalization for HF or ACS, according to new data from the EAST-AFNET 4 trial.
However, early rhythm control was not effective in patients with fewer CV comorbidities compared with usual care, and therapy-related bradycardia and drug toxicity also increased.
“Rhythm control therapy is often recommended for patients with symptoms to improve quality of life, and it is also recommended to patients who are younger and healthier,” Andreas Rillig, MD, cardiologist at University Heart and Vascular Center, University Medical Center Hamburg-Eppendorf, Germany, said during a press conference at Heart Rhythm 2022. “There are some safety concerns to treat patients with higher comorbidity levels with rhythm control therapy.”
As Healio previously reported, the main results of the EAST-AFNET 4 trial, presented at the 2020 European Society of Cardiology Congress, demonstrated that initiation of rhythm control therapy within 1 year of AF diagnosis in patients at risk for stroke lowered risk for CV events compared with usual care.
Risk by comorbidity burden
In a prespecified subanalysis of EAST-AFNET 4, researchers analyzed data from 2,789 patients with AF diagnosed within 1 year and concomitant conditions approximating a CHA2DS2-VASc score of at least 2, randomly assigned to systematic early rhythm control therapy (n = 1,395) or usual care (n = 1,394), including delayed, symptom-restricted rhythm control. Patients were stratified by low (< 4; n = 1,696) or high ( 4; n = 1,093) CHA2DS2-VASc score. The primary outcome was a composite of CV death, stroke and hospitalization with worsening HF or ACS.
For patients with a CHA2DS2-VASc score of 4 or greater, early rhythm control was associated with a 36% reduction in risk for the primary outcome, with an HR of 0.64 (95% CI, 0.51-0.81; P < .001). For patients with a CHA2DS2-VASc score of less than 4, early rhythm control did not impact risk for a primary outcome event (HR = 0.93; 95% CI, 0.73-1.19; P = .562; P for interaction = .037).
Differences in safety outcomes
There was no between-group difference in the primary safety outcome, a composite of death, stroke and serious adverse events related to rhythm control therapy, among patients with a high CHA2DS2-VASc score assigned to early rhythm control or usual care (HR = 0.84; 95% CI, 0.65-1.08; P = .175).
“There was even a trend toward a lower number of events in the patients treated with early rhythm control,” Rillig said.
However, among patients with a low CHA2DS2-VASc score, the primary safety outcome occurred more frequently among patients randomly assigned to early rhythm control therapy compared with usual care (HR = 1.39; 95% CI, 1.05-1.82; P = .019; P for interaction = .008).
In particular, patients with a low CHA2DS2-VASc score assigned to early rhythm control were more likely to experience drug toxicity related to AF treatment or drug-induced bradycardia vs. similar patients assigned to usual care and were significantly more likely to be hospitalized due to AF, Rillig said.
Rillig said the results are hypothesis-generating and suggest that older patients with recently diagnosed AF and multiple comorbidities should be preferentially treated with early rhythm control; however, dedicated trials are needed to validate the findings.
“It definitely makes sense to treat patients with higher comorbidity levels with early rhythm control because they derive the major benefit regarding reduction of CV endpoints,” Rillig said. “This finding does not mean that we should not treat symptomatic patients who are young. We have side effects, but we do not have a sign for higher death or stroke.”
Perspective
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Vivek Y. Reddy, MD
The original EAST-AFNET 4 was such a transformative study and its impacts have not even been felt yet. The community is just starting to understand it. However, questions remain: For someone older with high levels of comorbidities, does it make sense to make the effort to get that person into sinus rhythm? In that context, this is an important subanalysis.
The data show that patients with high comorbidity levels actually do derive a lot of benefit from early rhythm control. Importantly, they retain the benefit without an increase in safety events.
It is important to remember that patients with low comorbidity levels experience lower event rates overall. When you have lower event rates, you need more patients to prove anything. There were not enough patients with low comorbidity levels to say if they derive benefit or not.
Also, the original EAST-AFNET 4 study showed no difference in benefit by age groups. Operationally, if you have a low comorbidity index, then yes, perhaps it is not as critical to achieve rhythm control. The flipside is, this may be the time when it is easiest to achieve rhythm control. The longer you wait for a patient to go from low comorbidity to high before you intervene, the greater the chances are lower of achieving rhythm control.
It would be inappropriate to conclude from this analysis that young people do not benefit from early rhythm control. We are learning from other studies that the earlier you treat patients, the better your chances of success. The takeaway is not to avoid treating just because someone is older and has a high comorbidity index.
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Rillig A, et al. Late Breaking Clinical Trials: Updates and Registries. Presented at: Heart Rhythm 2022; April 29-May 1, 2022; San Francisco (hybrid meeting).
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