I'm Safia Chatur, Cardiologist at Massachusetts General Hospital and Instructor in Medicine at Harvard Medical School from Boston, Massachusetts. I'm pleased to discuss the risk benefit trade-off of finerenone across the spectrum of kidney function in the FINEARTS-HF trial.

What was the rationale for investigating finerenone specifically across the spectrum of kidney function in patients with HFmrEF/HFpEF?

Heart failure and chronic kidney disease frequently coexist and jointly contribute to increased risks of cardiovascular events, a progression of kidney disease and mortality. Such patients often face higher rates of premature drug discontinuation in part related to uncertainties around the safety and efficacy of guideline-directed medical therapy in this population, and this is particularly true of mineralocorticoid receptor antagonists or traditional mineralocorticoid receptor antagonists.

Widespread use of the steroidal MRA spironolactone has been particularly challenging in patients with heart failure and chronic kidney disease due to concerns about increased risks for hyperkalemia and worsening renal function. Finerenone is a non-steroidal MRA, a class of medications with different physiochemical properties, and so we wanted to better understand how chronic kidney disease may alter the risk benefit profile of finerenone, specifically in patients with mildly reduced and preserved ejection fraction.

Could you describe the study design and patient population of FINEARTS-HF, particularly focusing on the kidney function subgroups analyzed?

The FINEARTS-HF trial was a global randomised trial which enrolled patients with NYHA 2-4 heart failure with mildly reduced and preserved ejection fraction with an eGFR as low as 25. Patients were randomised to finerenone or placebo. Finerenone was titrated to a maximum dose of 20 milligrammes in patients with an eGFR less than or equal to 60 and a maximum dose of 40 milligrammes in patients with An eGFR greater than 60.

In this post hoc analysis of the FINEARTS-HF trial, we evaluated the relative and absolute treatment benefits of finerenone versus placebo on cardiovascular and safety outcomes across the spectrum of kidney function.

What were the key findings regarding the efficacy and safety of finerenone across different levels of kidney function?

There were three key messages. Patients at the lowest eGFR categories experienced the highest rates of cardiovascular events. Number two: both the relative and absolute treatment effects of finerenone relative to placebo on cardiovascular outcomes did not significantly differ across baseline kidney function. And three: while the absolute risks of hyperkalemia were amplified in the lowest eGFR categories, the risk of an adverse event leading to discontinuation were similar across the spectrum of kidney function.

What are the clinical implications of these results for managing patients with HFmrEF/HFpEF who have varying degrees of kidney function?

Despite being at high risk of adverse cardiovascular events, patients at this intersection of heart failure and kidney disease often face high rates of premature drug discontinuation or failure to initiate therapy altogether.

The main take-home message of this analysis is that the risk benefit trade-off of finerenone appears favourable and so kidney function alone should not detract from the initiation of finerenone. However, more frequent monitoring and dose adjustment at the lower eGFR categories may be required.

These data also highlight the importance of strategies to improve treatment persistence of MRA, particularly in these high-risk patients with chronic kidney disease. This includes the use of novel potassium binders as well as combination therapy with SGLT2 inhibitors, which has been shown to potentially mitigate the risk of hyperkalemia and enable more broad use of MRA, a strategy which might be particularly useful in patients with chronic kidney disease.

What further research questions emerge from these findings, and what next steps would you recommend in this therapeutic area?

The use of MRAs in heart failure care more broadly remains suboptimal and this is evident, a trend that is evident across healthcare registries globally. Considerations around the implementation of MRA use is a key next step as we start to think about real world implementation, cost is an important barrier.

While non-steroidal MRAs may have improved tolerability relative to steroidal MRAs, cost may be prohibitive and so a key question among many minds is, is there a class effect? The SPIRIT-HF trial and SPIRRIT-HFpEF trials which are ongoing will provide more data around the use of spironolactone in patients with preserved ejection fraction heart failure specifically.

What about the use of finerenone across various clinical settings? The ongoing MOONRAKER programme will provide insight on the use of finerenone across various clinical settings, among 15,000 patients including those hospitalised with heart failure, including among those with combination SGLT2 inhibitor therapy and in patients with heart failure with reduced ejection fraction who are intolerant or ineligible for steroidal MRA.

Lastly, zooming out, taking a 10,000 foot view of cardiovascular care, there is great imperative to develop best practise in drug implementation alongside data informing safety and efficacy and that involves exploring innovative new strategies which integrate digital technologies: principles from implementation science, and behavioural economics, and learning health systems in order to reduce clinical inertia and optimise cardiovascular care at scale at the population level.