What is the preferred initial approach for managing atrial fibrillation according to the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) trial?

AFFIRM Trial: Key Findings and Clinical Implications

Primary Finding

The AFFIRM trial demonstrated that rate control with anticoagulation is non-inferior to rhythm control for mortality and stroke prevention in patients with atrial fibrillation, and may actually be safer due to fewer hospitalizations and adverse drug effects. 1, 2

Trial Design and Patient Population

The AFFIRM (Atrial Fibrillation Follow-up Investigation of Rhythm Management) trial enrolled 4,060 patients with a mean age of 69.7 years who had atrial fibrillation and high risk for stroke or death 1, 2. Key patient characteristics included:

• 70.8% had hypertension 2
• 38.2% had coronary artery disease 2
• 64.7% had left atrial enlargement 2
• 26.0% had depressed left ventricular function 2
• Mean follow-up was 3.5 years 1, 2

Mortality Outcomes: No Difference Between Strategies

The primary endpoint of all-cause mortality showed no significant difference between groups 1, 2:

• Rate control group: 310 deaths (21.3% at 5 years) 1, 2
• Rhythm control group: 356 deaths (23.8% at 5 years) 1, 2
• Hazard ratio: 1.15 (95% CI: 0.99-1.34; p=0.08) 2

Notably, there was a trend toward increased mortality in the rhythm-control group, particularly among patients older than 65 years, those without congestive heart failure, and those with coronary heart disease 1.

Stroke and Thromboembolic Events: Anticoagulation is Critical

Stroke rates were similar between groups 1, 2:

• Rate control: 88 strokes/embolic events 1
• Rhythm control: 93 strokes/embolic events 1

The critical finding: 70% of all strokes occurred in patients who had stopped anticoagulation or had subtherapeutic INR (<2.0) 1, 2. This demonstrates that anticoagulation must be continued regardless of rhythm strategy, as clinically silent AF recurrences were common even in the rhythm-control group 1.

Rhythm Control Limitations and Adverse Effects

Despite aggressive rhythm control attempts, only 63% of patients in the rhythm-control group maintained sinus rhythm at 5 years (compared to 35% in rate control group) 1. This means 37% failed rhythm control despite antiarrhythmic drugs 1.

The rhythm-control strategy had significant disadvantages 1, 2:

• More hospitalizations (p<0.001) 1, 2
• More adverse drug effects from antiarrhythmic medications 1, 2
• Higher treatment burden without mortality benefit 2

Rate Control Efficacy and Drug Selection

In the rate-control arm, adequate rate control was achieved in the majority of patients, but required frequent medication adjustments 3:

• Beta-blockers were most effective: 70% achieved rate control (with or without digoxin) 3
• Calcium channel blockers: 54% achieved rate control (with or without digoxin) 3
• Digoxin alone: 58% achieved rate control 3
• Overall, 58% achieved adequate rate control with first drug or combination 3

Beta-blockers were superior to other drug classes and had fewer switches to alternative agents (p<0.0001) 3.

Heart Failure Outcomes: No Difference

Heart failure development or deterioration did not differ significantly between strategies 1:

• Rate control: 2.1% developed heart failure 1
• Rhythm control: 2.7% developed heart failure 1
• Hospitalization for heart failure: 3.5% (rate control) vs 4.5% (rhythm control) 1

Clinical Practice Recommendations Based on AFFIRM

Rate control with chronic anticoagulation is the recommended initial strategy for the majority of patients with atrial fibrillation 1. This recommendation is based on:

1. No mortality benefit from rhythm control 1, 2
2. Lower hospitalization rates with rate control 1, 2
3. Fewer adverse drug effects with rate control 1, 2
4. Difficulty maintaining sinus rhythm despite aggressive therapy 1

When to Consider Rhythm Control

Rhythm control remains appropriate for specific situations 1:

• Highly symptomatic patients despite adequate rate control 1
• Younger patients without significant comorbidities 1
• Hemodynamic instability (symptomatic hypotension, angina, acute heart failure) requiring immediate cardioversion 1
• Patient preference after informed discussion of risks and benefits 1

Critical Anticoagulation Mandate

Anticoagulation must be continued indefinitely in high-risk patients regardless of rhythm strategy chosen 1, 2. The AFFIRM trial clearly demonstrated that most strokes occurred when anticoagulation was stopped or subtherapeutic, even in patients believed to be in sinus rhythm 1, 2.

Common Pitfalls to Avoid

• Never discontinue anticoagulation based solely on apparent sinus rhythm maintenance, as asymptomatic AF recurrences are common 1, 2
• Do not assume rhythm control provides stroke protection without anticoagulation 1, 2
• Avoid pursuing aggressive rhythm control in older patients with multiple comorbidities, as they showed trend toward worse outcomes 1
• Do not overlook rate control as "giving up"—it is evidence-based first-line therapy with better safety profile 1, 2

Intensity of Rate Control

Subsequent analysis comparing AFFIRM's stricter rate control targets (resting HR ≤80 bpm) versus RACE's more lenient approach (resting HR <100 bpm) found no significant difference in clinical outcomes 4. However, patients with mean heart rates ≥100 bpm had worse outcomes than those with rates <100 bpm (hazard ratio 0.58 for <100 vs ≥100 bpm) 4.