Recent AF diagnosis and multiple comorbidities warrants early rhythm control strategy

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EAST-AFNET 4 chief investigator Paulus Kirchhof

Patients with recently diagnosed atrial fibrillation (AF) with a high burden of comorbidities should be considered for early rhythm control to reduce cardiovascular outcomes, whereas those with fewer comorbidities may have less favourable outcomes with this strategy.

These are among the conclusions drawn from a subanalysis of the EAST-AFNET 4 trial published this month in Circulation and authored by Andreas Rillig (University Medical Center Hamburg–Eppendorf, Hamburg, Germany) et al.

In their paper, Rillig and colleagues compared the effectiveness and safety of early rhythm control with usual care, stratifying into patients with a higher burden of comorbidities (CHA2DS2-VASc score ≥4) and those with a lower burden of comorbidities.

Rhythm control therapy is typically delayed unless patients have persistent symptoms on otherwise effective rate control. EAST-AFNET 4 investigated whether rhythm control therapy—with antiarrhythmic drugs or ablation—delivered soon after diagnosis improves outcomes.

Results of the trial, delivered at 2020 European Society of Cardiology Congress (ESC 2020, 29 August–1 September, virtual) and published in The New England Journal of Medicine, led investigators to conclude that rhythm control therapy, initiated soon after diagnosis of AF, reduces cardiovascular complications without increasing time spent in hospital and without safety concerns.

In the latest analysis, Rillig et al report that there were a total of 1,093 patients with CHA2DS2-VASc score ≥4 (74.8±6.8 years, 61% female) and 1,696 with CHA2DS2-VASc score <4 (67.4±8.0 years, 37% female) randomised within the trial.

Early rhythm control was found to reduce the composite primary efficacy outcome of cardiovascular death, stroke, or hospitalisation in patients with CHA2DS2-VASc score ≥4 (early rhythm control [ERC], 127/549 patients with events; usual care [UC], 183/544 patients with events; hazard ratio [HR], 0.64 [0.51–0.81]; p<0.001) but not in patients with CHA2DS2-VASc score <4 (ERC, 122/846 patients with events; UC, 133/850 patients with events; HR, 0.93 [0.73–1.19]; p=0.56, P-interaction=0.037). The primary safety outcome of death, stroke, or serious adverse events of rhythm control therapy was not different between the study groups, researchers report.

“These prespecified subanalyses of EAST-AFNET 4 show that  systematic early rhythm control therapy reduces cardiovascular complications compared with usual care in patients with a high comorbidity burden, defined by a CHA2DS2-VASc score ≥4,” Rillig and colleagues write in their analysis of the findings.

These hypothesis-generating findings call for independent validation, the authors add, noting that “at face value”, they support a preferential use of early rhythm control.

“On the basis of these subanalyses of EAST-AFNET 4, patients with recently diagnosed AF and  multiple cardiovascular comorbidities should have rapid, priority access to rhythm control therapy to reduce cardiovascular outcomes,” Rillig et al conclude. “The safety signal identified in these analyses highlights the need to develop safer ways to deliver early rhythm control, especially in patients with few cardiovascular conditions, including techniques avoiding bradycardia-related events, AF hospitalisations, and drug toxicity. Specific trials are warranted to validate our hypothesis.”

Commenting on the findings of the study, Paulus Kirchhof (University Heart and Vascular Centre UKE Hamburg, Hamburg, Germany and University of Birmingham, Birmingham, UK) the chief investigator of the EAST-AFNET 4 trial, said: “Based on this subanalysis, we should preferentially consider systematic rhythm control therapy in patients with multiple comorbidities. This challenges the old paradigm of preferentially treating younger and healthier patients with AF. Future prospective trials are warranted to prospectively test these findings.”


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