PARIS – Beta-blocking drugs were as effective for improving survival in patients with moderately severe renal dysfunction as they were in patients with normal renal function in a meta-analysis of more than 13,000 patients, a finding that seemed to solidify the role for this drug class for essentially all similar heart failure patients, regardless of their renal function.
This evidence could reshape usual care because “renal impairment is often considered a barrier in clinical practice” for starting a beta-blocker drug in patients with heart failure with reduced ejection fraction (HFrEF),, said at the annual congress of the European Society of Cardiology.
“We have shown with sufficient sample size that beta-blockers are effective in reducing mortality in patient with HFrEF and in sinus rhythm, even in those with an eGFR [estimated glomerular filtration rate] of 30-44 mL/min per 1.73 m2,” said Dr. Kotecha, a cardiologist at the University of Birmingham (England). “The results suggest that renal impairment should not obstruct the prescription and maintenance of beta-blockers in patients with HFrEF.”
“This important study was a novel attempt to look at [HFrEF] patients with renal insufficiency to see whether they received the same benefit from beta-blockers as other patients, and they did. So renal insufficiency is not a reason to withhold beta-blockers” from these patients, commented, a heart failure physician and chief science and medical officer for the American Heart Association in Dallas. “The onus is on clinicians to find a reason not to give a beta-blocker to a patient with HFrEF because they are generally well tolerated and they can have enormous benefit, as we saw in this study,” she said in a video interview.
The analysis run by Dr. Kotecha and associates used data collected in 11 of the pivotal randomized, controlled trial run for beta-blockers during the 1990s and early 2000s, with each study comparing bucindolol, bisoprolol, carvedilol, metoprolol XL, or nebivolol against placebo. The studies collectively enrolled 18,637 patients, which the investigators whittled down in their analysis to 17,433 after excluding patients with a left ventricular ejection fraction below 50% or who were undocumented. The subgroup with HFrEF included 13,861 patient in sinus rhythm at entry, 2,879 with atrial fibrillation, and 693 with an unknown atrial status. The main analysis ran in the 13,861 patients with HFrEF and in sinus rhythm; 14% of this cohort had an eGFR of 30-44 mL/min per 1.73 m2 and 27% had an eGFR of 45-59 mL/min per 1.73 m2. The median age of all patients in the main analysis was 65 years, 23% were women, and their median left ventricular ejection fraction was 27%.
During follow-up of about 3 years, the impact of beta-blocker treatment on survival, compared with placebo, was “substantial” for all strata of patients by renal function, except for those with eGFRs below 30 mL/min per 1.73 m2. (Survival was similar regardless of beta-blocker treatment in the small number of patients with severe renal dysfunction.) The number needed to treat to prevent 1 death in patients with an eGFR of 30-44 mL/min per 1.73 m2 was 21, the same as among patients with an eGFR of 90 mL/min per 1.73 m2 or more, Dr. Kotecha said.
Among the subgroup of patients with atrial fibrillation, beta-blockers appeared to exert no survival benefit, compared with placebo. The investigators did not assess the survival benefits exerted by any individual beta-blocker, compared with the others, and Dr. Kotecha stressed that “my belief is that this is a class effect” and is roughly similar across all the beta-blockers used in the studies.
The analysis also showed good safety and tolerability of the beta-blockers in patients with renal dysfunction. The incidence of adverse events leading to treatment termination was very similar in the beta-blocker and placebo arms, and more than three-quarters of patients in each of the two subgroups with renal dysfunction were maintained on more than 50% of their target beta-blocker dosage.
Dr. Kotecha has been an advisor to Bayer, a speaker on behalf of Atricure, and has received research funding from GlaxoSmithKline and Menarini. Dr. Jessup had no disclosures.