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Effects of Finerenone With and Without Concomitant SGLT2 Inhibitor Use in Patients With Heart Failure
TAKE-HOME MESSAGE
- This prespecified analysis of the FINEARTS-HF trial investigated the effects of finerenone in patients with heart failure (HF) and an LVEF of 40% or greater, specifically focusing on the role of concurrent SGLT2 inhibitor use. Among 6001 patients, 13.6% were receiving SGLT2 inhibitors at baseline. After a median follow-up period of 2.6 years, finerenone reduced the risk of worsening HF events and cardiovascular death, regardless of SGLT2 inhibitor use (RRs, 0.83 with SGLT2 inhibitors and 0.85 without).
- These findings show the beneficial effects of finerenone, observed irrespective of SGLT2 inhibitor use, and suggest that combining finerenone with SGLT2 inhibitors may enhance cardiovascular protection in patients with HF.
abstract
This abstract is available on the publisher's site.
Access this abstract nowBACKGROUND
Patients with heart failure (HF) with mildly reduced or preserved ejection fraction face heightened long-term risks of morbidity and mortality. The sodium glucose-co-transporter-2 inhibitors (SGLT2i) and the non-steroidal mineralocorticoid receptor antagonist (MRA) finerenone have both been shown to reduce the risk of cardiovascular events in this population, but the effects of their combined use are not known.
METHODS
FINEARTS-HF was a randomized, double-blind, placebo-controlled trial of finerenone in patients with HF and left ventricular ejection fraction (LVEF) ≥40%. Baseline SGLT2i use was a prespecified subgroup. The primary outcome was a composite of total (first and recurrent) worsening HF events and cardiovascular death. We first assessed for evidence of treatment heterogeneity based on baseline SGLT2i use. We further examined SGLT2i uptake during the trial and evaluated the treatment effects of finerenone accounting for baseline and during trial use of SGLT2i in time-varying analyses.
RESULTS
Among 6,001 participants, 817 (13.6%) were treated with an SGLT2i at baseline. During 2.6-years median follow-up, treatment with finerenone similarly reduced the risk of the primary outcome in participants treated with an SGLT2i (rate ratio 0.83; 95% confidence interval 0.60 to 1.16) and without an SGLT2i at baseline (rate ratio 0.85; 95% confidence interval 0.74 to 0.98); Pinteraction=0.76. In follow-up, 980 participants initiated SGLT2i, which was less frequent in the finerenone arm compared with placebo (17.7% vs. 20.1%; hazard ratio 0.86; confidence interval 0.76 to 0.97). Time-updated analyses accounting for baseline and subsequent use of SGLT2i did not meaningfully alter the treatment effects of finerenone on the primary endpoint.
CONCLUSIONS
The treatment benefits of the non-steroidal MRA finerenone were observed irrespective of concomitant use of an SGLT2i. These data suggest that the combined use of SGLT2i and a non-steroidal MRA may provide additive protection against cardiovascular events in patients with HF with mildly reduced or preserved ejection fraction.
Additional Info
Disclosure statements are available on the authors' profiles:
Effects of the Non-Steroidal MRA Finerenone with and without Concomitant SGLT2 Inhibitor Use in Heart Failure
Circulation 2024 Sep 28;[EPub Ahead of Print], M Vaduganathan, BL Claggett, IJ Kulac, ZM Miao, AS Desai, PS Jhund, AD Henderson, M Brinker, J Lay-Flurrie, P Viswanathan, MF Scheerer, A Lage, CSP Lam, M Senni, SJ Shah, AA Voors, F Zannad, B Pitt, JJV McMurray, SD SolomonFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
Despite the high risks of mortality and hospitalization associated with heart failure with mildly reduced or preserved ejection fraction (HFmrEF/HFpEF), few evidence-based therapies are available. Recently, the Finerenone Trial to Investigate Efficacy and Safety Superior to Placebo in Patients With Heart Failure (FINEARTS-HF) demonstrated that finerenone, a nonsteroidal mineralocorticoid receptor antagonist (MRA), reduced the risk of total worsening heart failure (HF) events and cardiovascular death in patients with HFmrEF/HFpEF.1 During the conduct of this trial, the DELIVER and EMPEROR-Preserved trials demonstrated the beneficial effects of SGLT2 inhibitors in patients with HFmrEF/HFpEF, leading to recommendations for their use in European and American guidelines.2-5
In FINEARTS-HF, 13.6% of participants were prescribed an SGLT2 inhibitor at baseline, with 18.9% initiating treatment during follow-up. This raises the key question of whether the efficacy and safety of finerenone were modified by SGLT2 inhibitor use. Notably, there was no suggestion of a modification of the effect of SGLT2 inhibitors according to baseline MRA use in the DELIVER or EMPEROR-Preserved trials. In this context, the prespecified analysis according to background SGLT2 inhibitor use in FINEARTS-HF, published by Vaduganathan and colleagues, confirms that the benefits of finerenone were independent of SGLT2 inhibitor use.6 Notably, event rates were higher in patients on an SGLT2 inhibitor at baseline, likely reflecting higher rates of chronic kidney disease, type 2 diabetes, and recent hospitalization for HF in this group. SGLT2 inhibitors were also more likely to be initiated in the placebo group, likely driven by the higher risk of HF events and subsequent changes to therapy. Crucially, the concomitant prescription of finerenone and an SGLT2 inhibitor was safe, offering clinicians reassurance when initiating both therapies in patients with HFmrEF/HFpEF.
Ongoing trials will further our understanding of the combination of an SGLT2 inhibitor and MRA in patients with HFmrEF/HFpEF. The CONFIRMATION-HF trial (NCT06024746) is investigating the co-initiation of finerenone and SGLT2 inhibitors in patients hospitalized with HF, irrespective of LVEF. Additionally, the ongoing SPIRIT-HF (NCT04727073) and SPIRRIT (NCT02901184) trials of spironolactone may provide further insights into the combined use of an alternative MRA along with an SGLT2 inhibitor in patients with HFmrEF/HFpEF.
The central message of this prespecified analysis of the FINEARTS-HF trial is that the combined use of finerenone and SGLT2 inhibitors is a safe and effective approach for reducing the risk of worsening HF and cardiovascular death in patients with HFmrEF/HFpEF, providing clinicians with two pillars of therapy to manage this condition.
References