Beta-Blockers in Heart Failure Patients With Atrial Fibrillation: Do They Really Save Lives?

The development of heart failure (HF) in patients with atrial fibrillation (AF) is extremely common, with a prevalence that ranges from approximately 10% to 50%, depending on the severity of the HF and the assigned New York Heart Association Functional class.^1-6 HF in patients with AF is the result of neurohormonal activation and mechanical stretch, among other factors, and is associated with an increased risk of stroke.⁷ Because of the proven mortality benefit of beta-blockers in HF patients,^8-13 the findings of a recent study published in the Journal of American College of Cardiology – HeartFailure¹⁴ that cast doubt on their efficacy in HF/AF patients have become particularly relevant to clinical practice.

Current ACC/AHA guidelines for HF,^15,16 which do not differentiate between patients with and without AF, recommend beta blockade to reduce morbidity and mortality. AF guidelines^17,18 also recommend beta-blockers as first-line agents for rate control (not for mortality benefit) and especially for patients with comorbid HF-a “dual indication” for beta blockade. 

We are quickly learning, however, that all HF is not the same and that the effect of beta-blockers in patients with HF and AF is quite different from the effect in HF patients with normal sinus rhythm.

A recent meta-analysis from Reinstra and colleagues¹⁴ brought these differences to light. They included 4 randomized trials (CIBIS-II,¹² MERIT-HF,¹⁹ SENIORS²⁰) and the U.S. Carvedilol Trial¹¹ of beta-blockers in patients with HF (ejection fraction less than 40%). These trials covered the 4 currently approved beta-blockers for HF (bisoprolol, metoprolol extended-release, nevibolol, and carvedilol, respectively), and included a total of 8680 patients. After adjustment for confounding variables, beta blockade was not associated with a reduction in mortality across all patients (odds ratio [OR]=0.86; P=.28); in sinus-rhythm patients, however, there was a significantly lower mortality rate (OR=0.63; P<.0001). Furthermore, beta-blocker use was not associated with a reduction in HF hospitalizations in AF (OR=1.11; P=.44), whereas in patients experiencing sinus rhythm, a lower rate was observed (OR=0.58; P<.0001).

So we now stand at a difficult crossroads. Should we be taking patients with HF and AF off beta-blockers? Although this study was well conducted and included a large population, it would be premature to conclude that all patients with HF and AF should not be treated with a beta-blocker. Additional randomized studies are needed to definitely establish this. There are differences among beta-blockers, as well, and some (eg, bucindolol) have proved beneficial in comorbid HF and AF. It is becoming increasingly apparent, however, that HF is heterogeneous and that management should be individually tailored. 

So, the next time there is a patient in your clinic with AF and HF who cannot tolerate a beta-blocker, it may be worth a discussion with his or her cardiologist about whether the therapy can be safely discontinued.
 

References:
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