EBQ:AFFIRM

Under Review Journal Club Article

Wyse DG, et al. "A Comparison of Rate Control and Rhythm Control in Patients with Atrial Fibrillation". NEJM. 2002. 347(23):1825-1833.
PubMed Full text PDF

Clinical Question

Which is better for treating atrial fibrillation, rate control allowing Afib at a lower heart rate, or rhythm control by maintaining sinus rhythm?

Conclusion

Rhythm control for Afib offers no survival advantage over rate control, and rate control is potentially advantageous given the lower risk of adverse drug reactions with rhythm control medications.

Major Points

• AFFIRM was the largest trial comparing rate control vs rhythm control strategies in atrial fibrillation
• There was no survival advantage with rhythm control strategy; in fact, there was a trend toward increased mortality
• Rhythm control was associated with more hospitalizations and adverse drug effects
• The results challenged the prevailing assumption that maintaining sinus rhythm would improve survival
• Anticoagulation should be continued regardless of rhythm control strategy, as most strokes occurred after warfarin was stopped or when INR was subtherapeutic

Study Design

• Multicenter, randomized controlled trial

Population

N= 4060 (7401 patients eligible and offered enrollment)

• Rate control group N=2027
• Rhythm control group N=2033

Patient Demographics

• Mean age: 69.7
• Women: 39.3%
• Ethnic minority: 11.3%
• Predominant cardiac diagnosis:
  • CAD: 26.1%
  • Cardiomyopathy: 4.1%
  • HTN: 50.8%
  • Valvular disease: 4.9%
  • Other: 1.0%
  • None: 12.4%
• Duration of qualifying Afib >2days: 69.2%
• First episode of Afib: 35.5%

Inclusion Criteria

• Age 65 or older or risk factors for stroke or death
• Diagnosis of atrial fibrillation that was:
  • recurrent
  • likely to cause illness or death
  • likely to require extended treatment

Exclusion Criteria

• Contraindication to anticoagulation
• Unable to take at least 2 drugs in each treatment group
• Unable to immediately start therapy after randomization

Interventions

• Rhythm control group attempted to maintain sinus rhythm. Antiarrhythmic drugs including: amiodarone, disopyramide, flecainide, moricizine, procainamide, propafenone, quinidine, sotalol, and combinations of the drugs were all possible. Treating physicians were allowed to choose the drug of their choice. Cardioversion was allowed as necessary.

• Rate control group attempted to maintain heart rate of 80 bpm or less while resting and 110 bpm or less with walking. Beta blockers, calcium-channel blockerrs, digoxin or combinations of the drugs were allowed. Again treating physicians could chose the drug of their choice.
• Non-pharmacologic interventions such as ablation and pacing could be pursued after the failure of at least 2 drugs from either treatment group
• INR of 2-3 was anticoagulation goal
  • Rhythm control group had the option of discontinuing anticoagulation if sinus rhythm was maintained for at least 4 consecutive weeks
  • Rate control group was maintained on anticoagulation

Outcomes

Primary Outcome

• Overal mortality at 5 years
  • Rhythym control 23.8%
  • Rate control 21.3%
  • Hazard ratio of 1.15 for rhythm control group- not statistically significant (p=0.08)

Secondary Outcomes

• Composite of:
  • Death
  • Disabling stroke
  • Disabling anoxic encephalopathy
  • Major bleeding
  • Cardiac arrest
• No difference between the two groups

Criticisms & Further Discussion

• Enrolled an older population (mean age 70); results may not be generalizable to younger patients with symptomatic AF
• Antiarrhythmic drugs used (primarily amiodarone and sotalol) have significant toxicities that may have offset benefits of sinus rhythm
• Crossover rate was high: 37.5% of rhythm control patients were in AF at follow-up, and some rate control patients were in sinus rhythm
• Anticoagulation could be stopped in the rhythm control group at physician discretion, which may have contributed to stroke events
• Does not address whether rhythm control with newer, safer strategies (e.g., catheter ablation) would be beneficial

Funding

• National Heart, Lung, and Blood Institute (NHLBI)

See Also

• Ottawa Aggressive ED Cardioversion Protocol
• 48hr Cardioversion for Afib