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Rhythm control linked to superior long-term outcomes vs. rate control drug treatment

Issue: September 2012

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Results of an observational study that examined the comparative effectiveness of rhythm control vs. rate control drug treatment on mortality in patients with atrial fibrillation suggest that there was little difference in mortality within 4 years of treatment, but rhythm control may be associated with more effective long-term outcomes.

“Controversy continues concerning the choice of rhythm control vs. rate control treatment strategies for AF. A recent clinical trial showed no difference in 5-year mortality between the two treatments. We aimed to determine whether the two strategies have similar effectiveness when applied to a general population of patients with AF with longer follow-up,” Raluca Ionescu-Ittu, PhD, of the Harvard School of Public Health, and colleagues wrote in the study.

The researchers used population-based databases from Quebec, Canada, from 1999 to 2007 to select patient aged 66 years and older hospitalized with AF. Patients did not have AF-related drug prescriptions in the year before they were hospitalized, but received a prescription within 7 days of discharge.

The 26,130 patients were followed for a mean of 3 years. During that time, there were 13,237 deaths (49.5%). After adjustment, researchers found that the effectiveness of rhythm vs. rate control drugs changed over time. There was a small increase in mortality among patients treated with rhythm control in the first 6 months following initiation (HR=1.07; 95% CI, 1.01-1.14), after which mortality was similar until year 4. After 5 years, mortality decreased steadily among patients treated with rhythm control (HR=0.89; 95% CI, 0.81-0.96) through 8 years (HR=0.77; 95% CI, 0.62-0.95).

“For the first 4 years after treatment initiation, our results in a population-based sample are similar to the results from the recent clinical trials. In addition, we found a tendency toward a long-term protective effect for rhythm control drugs. The long-term benefits of rhythm control drugs in AF found in this study need to be assessed in future studies,” the researchers wrote.

In an accompanying editorial, Thomas A. Dewland, MD, and Gregory M. Marcus, MD, MAS, of the University of California, San Francisco, asked: “How do we best interpret this unexpected result given contrary evidence from prior randomized trials?

“Although the findings … are provocative, they are insufficient to recommend a universal rhythm control strategy for all patients with AF. Randomization is a powerful tool that unfortunately cannot be reliably produced with statistical modeling,” they wrote in the editorial.

For more information:

Ionescu-Ittu R. Arch Intern Med. 2012;doi:10.1001/archinternmed.2012.2266.

Dewland TA. Arch Intern Med. 2012;doi:10.1001/archinternmed.2012.2332.

Disclosure: This research was supported by grants from the Canadian Institutes for Health Research to principal investigators. Some researchers also disclosed support and affiliations; see the full study for details. Dr. Marcus is a consultant for In-Carda Therapeutics and reports receiving research support from Astellas, Gilead and St. Jude Medical.