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Beta-blockers safe, effective for certain patients with HFrEF, reduced renal function

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PARIS — Beta-blockers reduced mortality in patients with sinus rhythm and HF with reduced ejection fraction, even in those with moderately severe renal dysfunction, according to the results of a meta-analysis using patient-level data conducted by the BB-meta-HF Collaborative Group.

Therefore, renal impairment should not be considered a barrier to the prescription of beta-blockers for patients with HFrEF, Dipak Kotecha, MBChB, PhD, PCAP, MSc, MRCP, FHEA, FESC, a clinician scientist in cardiovascular medicine at the University of Birmingham and National Institute for Health Research (NIHR) fellow, said during a presentation at the European Society of Cardiology Congress.

Moreover, discontinuation was similar in both beta-blocker and placebo groups, and beta-blockers were not associated with worsening renal function, Kotecha said.

“The problem with renal dysfunction is that it is so common that we often forget about it in our heart failure patients,” he said. “But we need to remember because it is associated with worse outcomes, and the real problem is that most of the randomized trials that we base our heart failure management on have excluded patients with renal impairment. That is a problem because if we want to look at patients with moderate or moderately severe renal dysfunction, we’re left with insufficient information.”

To try to get answers about beta-blockers in patients with HFrEF and impaired renal function, Kotecha and colleagues pooled data from 11 trials of 17,433 patients (median age, 65 years; 23% women; median left ventricular EF, 27%). The patients were stratified by baseline heart rhythm.

Of note, Kotecha said, only 11% of patients had preserved renal function, defined as an estimated glomerular filtration rate (eGFR) of 90 mL/min/1.73 m² or higher.

According to the meta-analysis, there was a 12% increase in mortality risk in patients with HFrEF for every 10 mL/min/1.73 m² lower eGFR (95% CI, 10-15). Kotecha noted there was a twofold increase in death for patients with an eGFR of 35 mL/min/1.73 m² compared with patients with eGFR of 60 mL/min/1.73 m², and that patients with low eGFR tended to die of HF-related causes while patients with high eGFR most commonly died from sudden causes.

In patients who were in sinus rhythm, beta-blockers were associated with reduced mortality risk compared with placebo across most strata of eGFR (P for interaction = .021), according to the researchers. Kotecha said the benefit was most pronounced in those with moderately severe or moderate renal dysfunction, and the number needed to treat was similar in patients with moderately severe renal dysfunction and in those with normal renal function (21.4 vs. 21.5, respectively).

In patients with atrial fibrillation, eGFR was lower than for the sinus rhythm cohort, and mortality at a mean follow-up of 1.3 years was higher (21% vs. 16%), Kotecha said, noting beta-blockers had no impact on mortality in the AF cohort regardless of eGFR (P for interaction = .18).

Study drug discontinuation in the beta-blocker group was numerically lower than in the placebo group across various renal function strata, according to the researchers.

“Renal dysfunction is a big problem in heart failure because it changes our thoughts on commencing, uptitrating and maintaining therapy for heart failure,” Kotecha said. “In this study, we’ve shown conclusively with sufficient power than even patients who have moderately severe renal dysfunction ... can benefit from beta-blockers if they have heart failure with reduced ejection fraction and sinus rhythm. The benefit we saw had the same impact on patients whether they had moderately severe or moderate renal dysfunction or preserved renal function.” – by Scott Buzby

Reference:

Kotecha D, et al. Hot Line Session 4. Presented at: European Society of Cardiology Congress; Aug. 31-Sept. 4, 2019; Paris.

Disclosure: Kotecha reports he received grants to support administration from Menarini Farmaceutica, data extraction support from GlaxoSmithKline, a collaborative research grant from IRCCS San Raffaele and speaker fees from Atricure, and serves as an advisory board member for Bayer.