Recent developments in the treatment of heart failure have stirred a renewed interest in the potential of targeted pharmacological strategies. One such agent, finerenone (Kerendia), has been subjected to significant scrutiny in clinical trials, particularly regarding its renal benefits for patients with heart failure and either mildly reduced or preserved ejection fraction. Findings from the FINEARTS-HF trial suggest that finerenone may not confer the anticipated renal benefits, casting a shadow over its role in this patient population.
Details from the FINEARTS-HF Trial
The secondary analysis of the FINEARTS-HF trial revealed disappointing results regarding finerenone’s ability to improve kidney health among heart failure patients. The trial found a concerningly higher incidence of a prespecified composite kidney outcome in those treated with finerenone compared to placebo; specifically, 75 events occurred in the finerenone group versus 55 in the placebo group (Hazard Ratio [HR] 1.33, 95% Confidence Interval [CI] 0.94-1.89). Similarly, a broader analysis incorporating declines in estimated glomerular filtration rate (eGFR) revealed 41 versus 31 events, maintaining a compelling trend favoring placebo over finerenone (HR 1.28, 95% CI 0.80-2.05).
In presenting these findings, Finnian R. McCausland from Brigham and Women’s Hospital emphasized that participants in the study were already considered to be at low risk for adverse kidney events. This assessment raises critical questions regarding the effectiveness of finerenone in a population that may have limited need for interventions targeting renal outcomes.
Chronic kidney disease (CKD) and heart failure are frequently intertwined, with approximately 50% of heart failure patients exhibiting some form of CKD. The implications of these findings are profound, as the presence of CKD is linked to a marked increase in morbidity and mortality. McCausland’s comments highlighted the importance of albuminuria, noting that its presence and severity serve as potent predictors for adverse cardiovascular and renal outcomes. This underscores the complexity and interrelated nature of these health issues, suggesting that merely targeting one condition may not sufficiently address the broader health spectrum experienced by these patients.
Despite its limited impact on overall composite kidney outcomes, finerenone did show potential in reducing the incidence of new-onset microalbuminuria (HR 0.76, 95% CI 0.68-0.83) and macroalbuminuria (HR 0.62, 95% CI 0.53-0.73). Moreover, the drug effectively reduced urine albumin-creatinine ratio (UACR) by approximately 30% over a six-month period, with these initial gains largely sustained throughout 36 months of follow-up.
The issue of albuminuria management raises speculative discussions among nephrologists. Ian de Boer from the University of Washington, who was not involved in the trial, noted that the reduction in albuminuria may eventually yield long-term eGFR benefits, although he cautioned that substantial renal improvements in this low-risk population might remain unlikely. The importance of considering long-term follow-up in CKD treatment is critical given its chronic nature, often advancing slowly over years or decades.
Regulatory Milestones and Future Research Directions
In the context of its regulatory journey, finerenone made history in 2021 by becoming the first non-steroidal selective mineralocorticoid receptor antagonist. It was approved specifically for reducing risks of sustained declines in eGFR and other cardiovascular outcomes in individuals with CKD linked to type 2 diabetes. Earlier analyses presented at the European Society of Cardiology highlighted finerenone’s efficacy in lowering urgent heart failure care and cardiovascular-related mortality (rate ratio 0.84, 95% CI 0.74-0.95).
As researchers reflect on the findings of the FINEARTS-HF trial, several questions emerge about the future role of finerenone in treating chronic conditions, particularly regarding its nephroprotective properties. There remains a crucial need for investigations that further explore long-term outcomes, dose-response relationships, and potential effects on diverse patient populations.
The findings of the FINEARTS-HF trial signify a pivotal moment in the investigation of finerenone for heart failure patients with mild renal impairment. While the initial enthusiasm around its kidney outcomes warrants careful re-evaluation, the findings also echo a broader narrative in nephrology and cardiology—the need for targeted treatment plans that comprehensively address the multifaceted nature of these chronic diseases. Future studies must aim to clarify the long-term renal benefits of finerenone and refine therapeutic strategies for managing heart failure in the context of CKD.
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