AFFIRM (2002): Rate versus Rhythm Control

Clinical question: in patients at risk of stroke or death, what effect does rate or rhythm control of atrial fibrillation have on mortality?

Study design: multi-centre, randomized, parallel group controlled trial

Inclusion criteria:

• Age > 65
• Patients with AF likely to be recurrent and result in illness or death, for which long-term treatment was warranted
• Presence of other risk factors for stroke or death

Exclusion criteria:

• Anticoagulation contraindicated
• Patients who could not receive ≥ 2 drugs for either treatment strategy

Groups:

• Rhythm control: sinus rhythm maintained via pharmacotherapy or cardioversion. Continuous anticoagulation encouraged, but could be stopped if sinus rhythm maintained for at least four (preferably 12) weeks.
• Rate control: pharmacotherapy to maintain HR ≤ 80 at rest and ≤ 110 during a six-minute walk test, plus continuous anticoagulation with a target INR of 2 – 3.

Patient characteristics:

• 4060 patients, 2033 in rhythm control and 2027 in rate control group
• Average age 69.7, 39.3% female

Outcomes and results:

• Average follow-up 3.5 years, maximum of 6 years
• Primary endpoint: overall mortality at 5 years – no difference (p = 0.08)
  • Trend toward higher mortality in rhythm control group
• Secondary endpoints:
  • Composite of death, disabling stroke, disabling anoxic encephalopathy, major bleeding, cardiac arrest – no difference (p = 0.33)
  • Hospitalization – rhythm control 80%, rate control 73% (p < 0.001)
  • Ischaemic strokes – no difference
  • Intracranial haemorrhage – no difference

Limitations:

• Not generally applicable to younger patients or patients without other risk factors for stroke
• Patients deemed by investigators to be unsuitable for either arm in the study may not have been selected for inclusion – selection bias
• High prevalence of sinus rhythm in both groups – patients with paroxysmal AF included

Conclusions: in patients older than 65 with atrial fibrillation and other risk factors for stroke, a rhythm control strategy offers no mortality benefit over a rate control strategy.

Reference: Wyse DG, Waldo AL, DiMarco JP, Domanski MJ, Rosenberg Y, Schron EB, Kellen JC, et al. A comparison of rate control and rhythm control in patients with atrial fibrillation. N Engl J Med. 2002;347(23):1825-33