Beta-Blockers Have No Benefit in HF Patients With Atrial Fibrillation

Shelley Wood

September 03, 2014

BARCELONA, SPAIN — Beta-blockers are of zero benefit in patients with heart failure and reduced ejection fraction if they also have atrial fibrillation[1].

Those are the persuasive findings of a large and meticulously conducted meta-analysis that, according to one commentator, sets a new bar for how these types of analyses should be done.

Dr Dipak Kotecha (University of Birmingham, UK) presented the analysis Tuesday during the final clinical-trial-update session of the European Society of Cardiology (ESC) 2014 Congress ; it was published simultaneously in the Lancet.

As he reminded a standing-room-only auditorium, atrial fibrillation and heart failure are "two emerging epidemics of the 21st century" and often coexist. Yet no study has ever specifically addressed whether beta-blockers, a mainstay of care in heart failure with reduced ejection fraction (HFrEF), are safe and effective when patients also have AF.

Patient-Level Data

Kotecha and colleagues pulled individual patient data from 10 randomized controlled trials that compared beta-blockers and placebo in HFrEF that included data on all-cause mortality and included a minimum of 300 patients and at least six months of follow-up. In all, 18 254 patients could be included in the analysis: 13 946 of whom were in sinus rhythm at the study outset and 3066 of whom had atrial fibrillation.

After a mean follow-up of 1.5 years, 16% of patients in sinus rhythm (non-AF patients) had died, compared with 21% of those with atrial fibrillation. When deaths were analyzed according to beta-blocker use vs placebo, beta-blockers were associated with a 27%, highly significant reduction in all-cause death among patients in normal sinus rhythm. By contrast, however, among patients with AF, no mortality reduction was seen for the group as a whole or for a wide-range of subgroup analyses that included age, sex, LVEF, NYHA class, heart rate, and other medical therapies.

Further analysis indicated significant reductions with beta-blockers in cardiovascular death, first CV hospital admission, and first HF-related hospital admission for patients in normal sinus rhythm, but here again, no such reductions were seen among patients with atrial fibrillation.

"Based on our findings, beta-blockers should not be used preferentially over other rate-control medications and not regarded as standard therapy to improve prognosis in patients with concomitant heart failure and atrial fibrillation," Kotecha and colleagues conclude.

Guidelines Say Otherwise

A "cause for concern," they add, is that all current guidelines, including those from the ESC and the ACC/AHA, recommend beta-blockers in patients with HF and atrial fibrillation. However, no signal of harm was seen with beta-blockers in these patients—and that should reassure physicians who have patients needing beta-blockers for other indications.

"However, for the primary reasons of preventing [major adverse cardiac events] MACE in patients with chronic HF and reduced LVEF, beta-blockers do not seem to be effective in patients with AF and should no longer be regarded as standard therapy to improve prognosis," they write.

So what should be used instead? That was one of the questions put to Kotecha by session moderator Dr Günter Breithardt (University of Münster, Germany) following Kotecha's presentation.

"Digoxin is the obvious alternative, [but] I think we need a trial to check that," Kotecha said. Some countries depend quite heavily on calcium-channel blockers (CCBs) over beta-blockers, including several countries in Eastern Europe, he added. In the UK, he continued, "we don't use CCBs in patients with HF because of some of the observational data suggesting increased mortality."

The discussant for the Kotecha's presentation, Dr Lars Rydén (Karolinska Institutet, Stockholm, Sweden), found little fault with the study, praising it as "an extremely well-performed meta-analysis; very few, I would say, live up to this standard."

The commitment to extracting patient-level data from all these studies sets a new bar for future meta-analyses, he continued. "I presume this must have taken several years of work and correspondence to perform."

Still, there are "some issues" that warrant further consideration, he added, pointing out that the mean age of the patients in the combined trials was relatively young: 64 for patients in sinus rhythm and 69 for those with AF. In the real world, AF patients tend to be considerably older yet are typically excluded from randomized clinical studies.

Ultimately, Rydén concluded saying he is highly encouraged by these results and, like Kotecha, called for a large randomized trial to settle the question.

Kotecha disclosed funding from the National Institute for Health Research in the UK. Disclosures for others are listed in the paper.


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