Impact of treatment crossovers on clinical outcomes in the rate and rhythm control strategies for atrial fibrillation: Insights from the AFFIRM (Atrial Fibrillation Follow‐up Investigation of Rhythm Management) trial

Abstract

We investigated the rates and reasons for crossover to alternative treatment strategies and its impact on mortality in patients who were enrolled in the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) trial. Over a mean follow-up period of 3.5 years, 842 patients underwent crossover to the alternative treatment arms in AFFIRM. The rate of crossover from rhythm to rate control (594/2,033, 29.2%) was more frequent than the rate of crossover from rate to rhythm control (248/2,027, 12.2%, P < 0.0001). The leading reasons for crossover from rhythm to rate control were failure to achieve or maintain sinus rhythm (272/594, 45.8%) and intolerable adverse effects (122/594, 20.5%). In comparison, the major reasons for crossover from rate to rhythm control were failure to control atrial fibrillation symptoms (159/248, 64.1%) and intolerable adverse effects (9/248, 3.6%). This difference in crossover pattern was statistically significant (P < 0.0001). There was a significantly decreased risk of all-cause mortality (adjusted HR: 0.61, 95% CI: 0.48-0.78, P < 0.0001) and cardiac mortality (adjusted hazard ratio [HR]: 0.61, 95% confidence interval [CI]: 0.43-0.88, P = 0.008) in the subgroup of patients who crossed over from rhythm to rate control as compared to those who continued in rhythm control. There was a nonsignificant trend toward decreased all-cause (adjusted HR: 0.76, 95% CI: 0.53-1.10, P = 0.14) and cardiac mortality (adjusted HR: 0.70, 95% CI: 0.42-1.18, P = 0.18) in patients who crossed over from rate to rhythm control as compared to those who continued rate control.

Strategies for Rhythm Control in Atrial Fibrillation

“…The landmark Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) trial, comparing these 2 strategies, failed to show a significant benefit for the rhythm control strategy over rate control. 8 However, subsequent subanalyses have suggested that although sinus rhythm is beneficial, this is offset both by adverse effects associated with antiarrhythmic drugs (AADs) used for the purpose as well as by the relatively poor efficacy of drugs in maintaining sinus rhythm in a good proportion of patients, 9, 10 In discussing the need for, as well as strategies for rhythm control in AF, it is useful to separately consider acute and chronic rhythm control.…”

The Care of Patients With Atrial Fibrillation and Heart Failure

“…Indeed, in both the A Comparison of Rate Control and Rhythm Control in Patients with Atrial Fibrillation (AFFIRM) and Rhythm Control versus Rate Control for Atrial Fibrillation and Heart Failure (AF-CHF) trials-the 2 landmark studies which investigated medical rate control versus medical rhythm control for the treatment of AF in the general population and in the HF population, respectively-worsening HF symptoms were the most common reasons to abandon a rate control strategy in favor of a rhythm control strategy. [10][11][12] Just as reversion to sinus rhythm may benefit patients with AF and HF, the development and persistence of AF may cause substantial harm. This is especially true for patients with HF with reduced ejection fraction (HFrEF) and AF.…”

Rate and rhythm control treatment in the elderly and very elderly patients with atrial fibrillation: an observational cohort study of 1,497 patients

“…Furthermore, we hypothesize that, because of the potential adverse drug effects (including lethal side effects) of antiarrhythmic drugs (AAD), older patients and those with more comorbidities are more likely to be prescribed a rate control strategy. 19,20…”