Week 2 – AFFIRM

“A Comparison of Rate Control and Rhythm Control in Patients with Atrial Fibrillation”

by the Atrial Fibrillation Follow-Up Investigation of Rhythm Management (AFFRIM) Investigators

N Engl J Med. 2002 Dec 5;347(23):1825-33. [NEJM free full text]

It seems like the majority of patients with atrial fibrillation that we encounter as residents today are being treated with a rate control strategy, as opposed to a rhythm control strategy. There was a time when both approaches were considered acceptable, and perhaps rhythm control was even the preferred initial strategy. The AFFIRM trial was the landmark study to address this debate.

Population: patients with atrial fibrillation (judged “likely to be recurrent”), age 65 or older “or who had other risk factors for stroke or death,” and in whom anticoagulation was not contraindicated

Intervention: rhythm control strategy with one or more drugs from a pre-specified list and/or cardioversion to achieve sinus rhythm

Comparison: rate control strategy with beta-blockers, CCBs, and/or digoxin to a target resting HR ≤ 80 and a six-minute walk test HR ≤ 110

– primary endpoint – death during follow-up (per Kaplan-Meier estimator)
– secondary endpoint – composite end point of death, disabling stroke, disabling anoxic encephalopathy, major bleeding, and cardiac arrest
– secondary analyses – primary end point in pre-specified subgroups (e.g. age ≥ 65, comorbid CAD, etc.)

4060 patients were randomized in this multi-center RCT. Death occurred in 26.7% of rhythm control patients versus 25.9% of rate control patients (HR 1.15, 95% CI 0.99 – 1.34, p = 0.08). The composite secondary endpoint occurred in 32.0% of rhythm control patients versus 32.7% of rate control patients (p = 0.33). Rhythm control strategy was associated a higher risk of death among patients older than 65 and patients with CAD (see Figure 2). Additionally, rhythm control patients were more likely to be hospitalized during follow-up (80.1% vs. 73.0%, p < 0.001) and to develop torsades de pointes (0.8% vs. 0.2%, p = 0.007).

A rhythm control strategy in atrial fibrillation offers no mortality benefit over a rate control strategy.

At the time of publication, the authors wrote that rate control was an “accepted, though often secondary alternative” to rhythm control. Their study clearly demonstrated that there was no significant mortality benefit to either strategy, that hospitalizations were greater in the rhythm control group, and in subgroup analysis that rhythm control led to higher mortality among the elderly and those with CAD. Notably, 37.5% of rhythm control patients had crossed over to rate control strategy by 5 years follow-up, whereas only 14.9% of rate control patients had switched over to rhythm control.

But what does this study mean for our practice today? Generally speaking, rate control is preferred in most patients, particularly the elderly and patients with CHF, whereas rhythm control may be pursued in patients with persistent symptoms despite rate control, patients unable to achieve rate control on AV nodal agents alone, and patients younger than 65. Both the AHA/ACC (2014) and the European Society of Cardiology (2016) guidelines have extensive recommendations that detail specific patient scenarios.

Further Reading:
1. Cardiologytrials.org
2. Wiki Journal Club
3. 2 Minute Medicine

Summary by Duncan F. Moore, MD

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