Early Rhythm Control Also May Help Lower-Risk AF Patients

Early rhythm control with ablation or antiarrhythmic drugs is associated with a lower risk of adverse cardiovascular outcomes compared with rate control in patients with newly diagnosed atrial fibrillation (AF), even when they have a low baseline risk of stroke, an observational study indicates.

The apparent benefits of such a strategy were observed regardless of whether patients would have been considered eligible or ineligible for the EAST-AFNET 4 trial, which demonstrated an advantage for early rhythm control over rate control. Some other trials, including ATHENA and CASTLE-AF, also have shown a reduction in CV outcomes with early rhythm control, although all of these trials have enrolled patients with stroke risk factors.

This new analysis, published online this week in Annals of Internal Medicine, “clearly showed that early rhythm control therapy was effective even in patients with low stroke risk,” Boyoung Joung, MD (Yonsei University College of Medicine, Seoul, South Korea), one of the senior authors, told TCTMD via email.

“We think that physicians should pursue early rhythm control in all patients diagnosed with AF regardless of CHA₂DS₂-VASc score,” he said, adding, however, that “additional studies about early rhythm control therapy might be needed in the elderly frail population.”

EAST-AFNET 4 trial enrolled patients with recently diagnosed AF and risk factors for stroke (median CHA₂DS₂-VASc score roughly 3), so there remain questions about how generalizable the findings might be to patients with few or no stroke risk factors.

The current study, with lead authors Daehoon Kim, MD (Yonsei University College of Medicine), and Pil-Sung Yang, MD (CHA University, Seongnam, South Korea), explored that question using claims data from the Korean National Health Insurance Service. The analysis included 54,216 patients who initiated rhythm control (ablation or antiarrhythmic drugs) or rate control within a year of being diagnosed with AF and survived for at least 180 days after the first prescription or procedure. Most patients (69.3%) were considered eligible for the EAST-AFNET 4 trial (median CHA₂DS₂-VASc score 4), and the remaining were deemed ineligible (median CHA₂DS₂-VASc score 1). Eligible patients were older (median age 70 vs 54) and less likely to be men (51% vs 84%) compared with their ineligible peers.

Catheter ablation was the initial method for rhythm control in just 0.9% of eligible and 1.6% of ineligible patients, with the proportions undergoing ablation at some point during follow-up reaching 4.9% and 12.4%, respectively. The rest of patients were managed with antiarrhythmic drugs, most commonly propafenone, flecainide, and amiodarone.

Through a median follow-up of roughly 3 years, early rhythm control versus rate control was associated with a lower risk of a composite of CV death, ischemic stroke, hospitalization for heart failure, or MI regardless of eligibility for EAST-AFNET 4:

• Eligible (weighted incidence rate 6.57 vs 7.68 events per 100 person-years; HR 0.86; 95% CI 0.81-0.92)
• Ineligible (weighted incidence rate 1.60 vs 2.00 events per 100 person-years; HR 0.81; 95% CI 0.66-0.98)

Risk of each of the individual components tended to be lower with early rhythm control, with the differences reaching statistical significance in the eligible population. The mean number of nights spent in the hospital each year was lower irrespective of eligibility as well.

There were no differences in safety outcomes between the rhythm and rate control strategies for either of the eligibility groups, “suggesting no need for trade-offs sacrificing safety for better cardiovascular outcomes,” the authors say.

Commenting for TCTMD via email, Peter Noseworthy, MD (Mayo Clinic, Rochester, MN), said “there is a growing consensus that early rhythm control strategies for AF may translate to better long-term outcomes. Although data are mixed, the EAST-AFNET 4 trial provided the best evidence that clinical outcomes are better when we take an aggressive early rhythm control strategy in patients with cardiovascular risk factors.”

But there was an open question regarding whether such benefits would also be seen in lower-risk patients, who experience fewer adverse outcomes overall. In this type of population, “it is much harder to demonstrate a benefit in the prospective clinical trials, since it is hard to power a trial for relatively infrequent endpoints,” Noseworthy said.

Nonetheless, despite the lack of randomized evidence in patients with low stroke risks, many patients with AF who choose rhythm control over rate control are on the lower end of the risk spectrum, he said.

“These patients may wish to pursue a rhythm control strategy for symptom control, but they often ask us if, in doing so, we will also reduce their risk of long-term cardiovascular events,” Noseworthy said. “The current study suggests that the benefits we expect in high-risk patients would also be seen in patients on the lower end of the risk spectrum.”

He cautioned that there’s the potential for residual confounding with any observational study, something the study authors also acknowledge. “I suspect, however, that we may never have definitive data from prospective trials in this low-risk population,” Noseworthy said. “I believe this study gives us one more data point to help us in our nuanced discussions with such patients.”