What were the outcomes of the EAST AFNET (Atrial Fibrillation Network) trial regarding early rhythm control in patients with atrial fibrillation?

EAST-AFNET 4 Trial Outcomes

Early rhythm control therapy in patients with recently diagnosed atrial fibrillation (within 12 months) significantly reduced major cardiovascular events compared to usual care, demonstrating a 21% relative risk reduction in the composite primary outcome of cardiovascular death, stroke, heart failure hospitalization, or acute coronary syndrome.

Primary Efficacy Outcomes

The EAST-AFNET 4 trial enrolled approximately 2,789-3,000 patients with AF diagnosed within the previous year who had cardiovascular risk factors (CHA₂DS₂-VASc score ≥2) 1, 2. The trial compared early rhythm control (antiarrhythmic drugs or catheter ablation initiated promptly) versus usual care (rate control with rhythm control reserved for persistent symptoms) 2.

Composite Cardiovascular Events

• Early rhythm control reduced the primary composite outcome of cardiovascular death, stroke, heart failure hospitalization, or acute coronary syndrome with a hazard ratio of approximately 0.79 compared to usual care 3
• The benefit was consistent across multiple subgroups, including patients with prior stroke (HR 0.52,95% CI 0.29-0.93) 1
• Real-world validation studies confirmed these findings, with adjusted hazard ratios of 0.823 for composite adverse events in a Taiwanese cohort of 301,064 patients 3

Stroke Prevention

• Early rhythm control was associated with lower ischemic stroke risk (aHR 0.771,95% CI 0.751-0.792) in real-world implementation 3
• Among patients with prior stroke history, early rhythm control reduced recurrent events from 7.4 to 3.7 per 100 person-years 1

Heart Failure and Mortality

• Heart failure hospitalization was reduced (aHR 0.851,95% CI 0.806-0.899) with early rhythm control 3
• All-cause mortality decreased significantly (aHR 0.794,95% CI 0.782-0.806) compared to usual care 3

Timing of Intervention Matters

The benefits of rhythm control were most pronounced when initiated within 3 months of AF diagnosis, with progressively diminishing advantages when delayed to 3-6 months, 7-9 months, or 10-12 months 3. This temporal relationship suggests that early intervention prevents irreversible atrial remodeling and preserves cardiac function 2.

Applicability Across Patient Populations

Asymptomatic Patients

• Early rhythm control provided similar benefits in asymptomatic patients (EHRA score I) as in symptomatic patients, with 30.4% of trial participants being asymptomatic at baseline 4
• The primary outcome occurred in 79/395 asymptomatic patients with early rhythm control versus 97/406 with usual care (HR 0.76,95% CI 0.6-1.03) 4
• This challenges traditional guideline restrictions limiting rhythm control to symptomatic patients only 4

Low-Risk Patients

• Benefits extended to patients with low stroke risk (CHA₂DS₂-VASc score 0-1) who would not have met EAST-AFNET 4 inclusion criteria 5
• In a Korean nationwide study of 16,659 low-risk patients, early rhythm control showed consistent benefit (HR 0.81,95% CI 0.66-0.98) 5

Safety Profile

• No significant differences in safety outcomes were observed between rhythm and rate control strategies 5
• Primary safety events (death, stroke, or serious adverse events related to rhythm control) occurred in 15% of early rhythm control patients versus 28% in usual care among those with prior stroke 1

Contrast with Historical Trials

This represents a paradigm shift from earlier trials (AFFIRM, RACE, PIAF, STAF) that showed no mortality benefit or even trends toward harm with rhythm control 6. The key differences explaining EAST-AFNET 4's success include:

• Earlier intervention (within 12 months vs. delayed approach in older trials) 2
• Modern rhythm control methods including catheter ablation and newer antiarrhythmic drugs 2
• Mandatory anticoagulation continuation regardless of rhythm status, addressing the major safety concern from AFFIRM where 70% of strokes occurred after anticoagulation discontinuation 6
• Structured follow-up with patient-operated ECG monitoring 2

Clinical Implementation Algorithm

For newly diagnosed AF patients (≤12 months):

1. Initiate anticoagulation immediately based on CHA₂DS₂-VASc score and continue indefinitely regardless of rhythm strategy 1, 2

2. Consider early rhythm control (within 3 months) for:

   • All patients with cardiovascular comorbidities (CHA₂DS₂-VASc ≥2) 3, 1
   • Symptomatic AND asymptomatic patients 4
   • Even low-risk patients (CHA₂DS₂-VASc 0-1) based on emerging evidence 5

3. Rhythm control options include:

   • Antiarrhythmic drugs as first-line 2
   • Catheter ablation for appropriate candidates 2
   • Combination approaches as needed 2

4. Maintain rate control therapy concurrently to manage breakthrough AF episodes 2

Critical caveat: The superior outcomes with early rhythm control depend on maintaining anticoagulation indefinitely, as silent AF recurrences remain common even with aggressive rhythm management 6, 1.