Beta-blockers may reduce mortality in patients with heart failure, renal dysfunction
Beta-blockers could reduce mortality risk in patients with heart failure with reduced ejection fraction (HFrEF) and moderate or moderately-severe renal dysfunction without causing harm, according to the BB-META-HF* trial presented at ESC 2019.
“We show conclusively that moderate or moderately-severe kidney dysfunction should not be a barrier to beta-blocker initiation or uptitration,” said principal investigator Dr Dipak Kotecha from the University of Birmingham, Birmingham, UK.
The multinational study population comprised 17,433 patients (median age 65 years, 23 percent female, median LVEF** 27 percent) with HFrEF from 10 randomized, double-blind controlled trials***, of whom 13,861 were in sinus rhythm and 2,879 had atrial fibrillation (AF).
Patients with AF had a lower eGFR# compared with those in sinus rhythm (median 60 vs 64 mL/min/1.73 m2), and 48.9 percent had an eGFR <60 mL/min/1.73 m2 compared with 42.9 percent of those with sinus rhythm. Patients with AF also had a higher mortality rate than those in sinus rhythm (21 percent vs 16 percent).
Over a mean 1.3-year follow-up, every 10 mL/min/1.73 m2 reduction in eGFR was associated with a 12 percent increased risk of death, primarily due to progressive heart failure in patients with severe renal dysfunction (eGFR <30 mL/min/1.73 m2). Sudden death was the most common cause of death among patients with preserved kidney function.
Among patients in sinus rhythm (LVEF <50 percent), beta-blockers reduced mortality risk by 27 percent (p<0.0001) and 29 percent (p=0.001) among patients with moderate (eGFR 45–59 mL/min/1.73 m2) and moderately-severe (eGFR 30–44 mL/min/1.73 m2) renal dysfunction, respectively, compared with placebo. [ESC 2019, FP number 4194]
The significant reduction in mortality with beta-blockers compared with placebo was seen across renal function (p<0.0001 and p=0.006 for patients with eGFR 60–89 and >90 mL/min/1.73m2, respectively), with the number needed to treat to prevent one death comparable between patients with moderately-severe dysfunction and preserved renal function (21.4 and 21.5, respectively).
Beta-blockers did not significantly reduce mortality risk compared with placebo in patients with AF regardless of renal function status (pinteraction=0.18), though beta-blockers did not exert any harm either.
Adverse events (AEs) leading to discontinuation occurred at a similar rate between patients receiving beta-blockers and placebo among those with moderate (14.8 percent vs 14.9 percent) and moderately-severe renal dysfunction (19.4 percent vs 20.9 percent), with a trend toward a higher rate of discontinuation among placebo than beta-blocker recipients with preserved renal function (15.1 percent vs 11.0 percent).
More than three-quarters of patients with moderate (77.9 percent) and moderately-severe renal dysfunction (76.3 percent) attained a >50 percent maximum targeted dose of beta-blockers, with 83.8 percent of those with preserved renal function attaining this dose.
Due to the limited number of patients with severe kidney disease, the researchers could not establish the efficacy and safety of beta-blockers in this group.
“Although there is no clear contraindication for most patients, it is not surprising that treatment initiation or uptitration of life-saving heart failure therapies is quite low in patients with coexisting renal dysfunction. Ironically, heart failure patients with impaired kidney function are at the highest risk of adverse outcomes and have potentially the most to gain from therapy,” said Kotecha.
“Most of the randomized trials that we base our clinical management on have excluded patients with significant renal impairment,” he said, noting that this has led to drawbacks pertaining to treating these patients.
“[The results show that] beta-blockers do not worsen renal dysfunction, even in patients with renal dysfunction at baseline,” said Kotecha. However, worsening renal dysfunction is accompanied by a higher mortality risk, which “highlights the importance of preserving kidney function by working with renal specialists,” he said.