Introduction and methods

Beta-blockers in high-risk heart failure patients with reduced ejection fraction and moderately-severe renal dysfunction

Presented at ESC Congress 2019 in Paris, France by Dipak Kotecha (Birmingham, United Kingdom)

Renal dysfunction is common in heart failure (HF) patients and it is associated with worse outcomes. Randomised trials typically exclude patients with significant renal impairment. Previous studies based on sub-groups of trials have had insufficient patients to make any robust conclusions on those with moderate or moderately-severe renal dysfunction. This has implications for clinicians and for the assumed effectiveness of treatment. This impacts prescription of guideline-recommended therapy, dosage given and the maintenance of drugs.

The Beta-blockers in Heart Failure Collaborative Group (BB-meta-HF) therefore examined the effect of renal dysfunction on outcomes in patients with HF and reduced ejection fraction (HFrEF), using the totality of individual patient data (IPD) from the landmark, double-blind, randomized controlled trials (RCT) comparing beta-blockers with placebo. BB-meta-HF is a multinational project that has systematically harmonized clinical trial data to improve management and outcomes in patients with HF. In this study, they test the hypothesis that compared to placebo, beta-blockers reduce mortality in HFrEF patients with moderate and moderately-severe renal dysfunction. Further, they look at the prognostic impact of renal dysfunction and associated variables, how change in renal function affects mortality, and the effect of heart rhythm.

Main results

• Renal dysfunction is a key marker of mortality, as shown by a graph that plots adjusted HR (cubic spline) and baseline eGFR, which depicts a declining slope, which flattens in higher eGFR ranges.
• In sinus rhythm, the beneficial effect of beta-blockers extends to patients with moderate and moderately severe renal impairment. This was shown in graphs for different eGFR categories, which showed significantly lower event curves for beta-blockers as compared with placebo, in all categories from eGFR 30-44 upwards (not in eGFR <30).
• Use of beta-blockers does not worsen renal function, even in those with reduced eGFR at baseline. In baseline eGFR categories up to 45-59 (including <30), eGFR is stable between baseline, interim, and final measurements.
• Worsening renal function was associated with much higher mortality.
• Patients with HFrEF and concomitant atrial fibrillation had no apparent benefit from beta-blockers at any level of eGFR.

Conclusions

This analysis demonstrated with a sufficient sample size that beta-blockers are effective in reducing mortality in patients with HFrEF and sinus rhythm, even in those with moderately-severe renal dysfunction (as low as an eGFR of 30-44 mL/min/1.73m²). Despite the higher rates of comorbidities, the absolute benefit in this group was similar to patients with preserved renal function. Discontinuation due to adverse events was the same for both beta-blockers and placebo in these double-blind trials and renal function did not appear to worsen, even in those with kidney dysfunction at baseline. Hence, these results suggest that renal impairment should not obstruct the prescription and maintenance of beta-blockers in patients with HFrEF.

Discussion

New medications are often used as additives to base therapies, such as ACE inhibitor and beta-blockers. Outcomes are dependent on the use of these base therapies. However, they are often not used and patients do not receive optimal treatment in this case.

Someone in the audience asked what the message to primary care is and Kotecha said that primary care physicians could be confident to give beta-blockers in patients with impaired renal function.

Would Kotecha expect any differences between beta-blockers? He did not think so: four are guideline-recommended therapies and a class effect has been observed for beta-blockers.

- Our reporting is based on the information provided at the ESC congress -