AFFIRM

Rate control vs rhythm control in atrial fibrillation
In older, higher-risk patients with AF, rhythm control did not improve survival compared with rate control and caused more hospitalizations and adverse drug effects. Anticoagulation remained critical regardless of apparent rhythm

Study design

  • Multicenter randomized trial
  • N = 4,060
  • Rhythm control vs rate control
  • Mean follow-up 3.5 years
  • Primary outcome: all-cause mortality

Population

Included
  • AF likely to recur
  • Long-term AF treatment warranted
  • Age ≥65 or another risk factor for stroke/death
  • Appropriate candidate for either rate or rhythm control
Typical patient
  • Older AF population
  • Hypertension common
  • Frequent CAD and structural heart disease
  • Higher thromboembolic risk
Mean age 69.7 39% women 71% HTN 38% CAD Warfarin era

Interventions

Rhythm control
  • Goal: restore and maintain sinus rhythm
  • Antiarrhythmic drugs
  • Cardioversion as needed
  • n = 2,033
Rate control
  • Goal: ventricular rate control
  • Beta-blocker, nondihydropyridine CCB, digoxin or combination
  • No routine attempt to maintain sinus rhythm
  • n = 2,027
Anticoagulation: Warfarin was initially used in both groups. In the rhythm-control strategy, anticoagulation could be stopped in selected patients maintaining sinus rhythm. Most ischemic strokes occurred after warfarin had been stopped or when INR was subtherapeutic

Primary outcome

All-cause mortality at 5 years
23.8% rhythm control vs 21.3% rate control
HR 1.15, 95% CI 0.99–1.34, P = 0.08

Rhythm control vs rate control

All-cause mortality at 5 years

30% 20% 10% 0%
23.8%
Rhythm control
21.3%
Rate control
23.8% vs 21.3%  |  HR 1.15  |  95% CI 0.99–1.34  |  P = 0.08

Rhythm control did not improve survival

Secondary outcomes

Ischemic stroke

Similar between strategies
Approximately 1%/year

Hospitalization

More frequent with rhythm control

Adverse drug effects

More frequent with rhythm control

Major composite outcome

No significant difference
P = 0.33

Clinical interpretation

  • Routine drug-based rhythm control did not improve survival
  • Rate control is reasonable in many older patients without a strong rhythm-control indication
  • Restoration of sinus rhythm does not eliminate thromboembolic risk
  • Do not stop anticoagulation solely because sinus rhythm has been restored
Key point: AFFIRM compared treatment strategies, not sinus rhythm itself. The trial does not show that maintaining sinus rhythm is harmful

Limitations

  • Predominantly older, higher-risk population
  • Rhythm control was primarily antiarrhythmic drug based
  • Predates modern AF ablation and contemporary early rhythm-control strategies
  • Anticoagulation discontinuation contributed to stroke events
  • Substantial crossover between treatment strategies
Modern rhythm control has evolved substantially. AFFIRM remains foundational for understanding rate vs rhythm control, but should not be interpreted as evidence against early rhythm control or catheter ablation in appropriately selected patients
Wyse DG, Waldo AL, DiMarco JP, et al. A Comparison of Rate Control and Rhythm Control in Patients with Atrial Fibrillation. N Engl J Med. 2002;347:1825–1833. doi:10.1056/NEJMoa021328. NEJM