January 30, 2017
By Scott Baltic
NEW YORK (Reuters Health) - In patients with atrial fibrillation (AF) and heart failure with a reduced ejection fraction (HFrEF), beta-blockers are associated with significantly lower all-cause mortality, new research confirms.
Hospitalizations and cardiovascular mortality were also reduced in the study, but not to a statistically significant extent, leaving the research team and other experts puzzled.
The findings were consistent whether AF was paroxysmal or persistent AF, of recent onset or long-standing, and was a high or low burden to patients.
Overall, the authors concluded, "These results support current evidence-based recommendations for beta-blockers in patients with HFrEF, whether or not they have associated AF," barring contraindications.
The results challenge the conclusions of a 2014 meta-analysis published in The Lancet that found, in contrast to current North American and European guidelines for treatment of patients with HFrEF, no association of beta-blockers with reduced mortality.
For the new study, as reported online January 11 in JACC: Heart Failure, researchers with the Universite de Montreal analyzed data from the Atrial Fibrillation and Congestive Heart Failure (AF-CHF) trial.
From the 1,376 participants in the trial, they identified 229 patients without beta-blocker therapy at baseline and a propensity-matched group of 426 patients who received metoprolol, carvedilol, or bisoprolol.
The primary intention-to-treat analysis found that beta-blockers were associated with a 28% reduction in all-cause mortality over a median follow-up of 37 months (hazard ratio 0.721, P=0.0180).
The AF-CHF trial was designed to compare rate-control to rhythm-control therapies in patients with HF and AF and was not intended to address the effect of beta-blockers on mortality, co-author Dr. Paul Khairy explained by email. Still, he said, "a strong association was identified between beta-blockers and all-cause mortality".
"Since similar trends were observed for cardiovascular mortality," Dr. Khairy added, "it is possible that statistical significance would have been achieved with a larger study population."
Why was all-cause mortality reduced to a greater extent than cardiovascular mortality? That remains "speculative," Dr. Khairy said. "The confidence limits overlap substantially," he noted, adding "it is possible that some cardiovascular deaths may have been misclassified as non-cardiovascular deaths."
Regarding the nonsignificant reduction in hospitalizations, Dr. Khairy said, "Our analyses suggest that salutary effects of beta-blockers were counter-balanced, in part, by a trend toward a higher rate of hospitalizations for AF," reflecting the AF-CHF trial design. Here again, he said, a larger sample size might have yielded a significant reduction in hospitalizations.
In their editorial titled, "Don't Bury the Beta-Blockers Just Yet," Dr. Jonathan P. Piccini of Duke University Medical Center in Durham, North Carolina and Dr. Larry A. Allen of the University of Colorado School of Medicine in Aurora called the lack of an apparent decrease in cardiovascular or heart failure hospitalization "a bit puzzling given the observed mortality benefit."
Their advice for clinicians caring for patients with AF and HF: "At present, we believe clinicians should initially default to prescribing evidence-based beta-blockers in all patients with HFrEF, regardless of AF status . . . . Beta-blockers have a variety of positive actions in patients with AF, including rate control and prevention of tachycardia-induced cardiomyopathy."
Dr. Peter Bronnum Nielsen of Aalborg University Hospital in Denmark, and Dr. Gregory Y.H. Lip of the University of Birmingham, England, noted in an email to Reuters Health that although the underlying mechanisms are not fully understood, the study population seemed to fare better with beta-blocker treatment for all measured outcomes, even though not all outcomes reached statistical significance.
"This indicates that the practice performed in the AF-CHF studied appeared to be safe, and does not hint at any reason to withhold beta-blocker treatment in an AF patient with concomitant CHF," they said.
The AF-CHF trial was funded by the Canadian Institutes of Health Research.
JACC: Heart Failure 2017.
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