FINEARTS for fine hearts

Mineralocorticoid receptor antagonists (MRA), such as spironolactone, have been recommended as one of the key treatments for people with heart failure with reduced ejection fraction (HFrEF) for more than a decade. The Randomized Aldactone Evaluation Study (RALES) was the first major randomised trial to demonstrate the benefit of spironolactone in people with HFrEF and the results were published all the way back in 1999 (when I was still doing my GCSEs)! 

However, there has been uncertainty about whether MRAs should also be offered to people who have heart failure with preserved or only mildly reduced ejection fraction, so called HFpEF and HFmrEF. The first randomised trial in this population was called TOPCAT; Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist. TOPCAT reported that spironolactone had not reduced the primary composite endpoint of cardiovascular death, heart failure hospitalisations or aborted cardiac arrest and so the MRAs were not recommended for treatment of HFpEF. 

The results of the TOPCAT trial have been a topic of debate. It was multi-national study conducted across six countries (United States, Canada, Brazil, Argentina, Georgia and Russia) and a large difference in results was found between regions with a positive outcome among all of the North and South American countries. This led to a question as to whether the lack of efficacy for spironolactone was actually due to the different methods used for recruiting and treating patients in Russia and Georgia. A question mark has therefore remained over the role of MRA in HFpEF. 

Step forward the FINEARTS-HF study, presented at this year’s European Society of Cardiology Congress in August. “Remind me what finerenone is?” I hear you ask. It is a type of MRA and therefore a sister drug to spironolactone. However, whilst spironolactone is a steroidal and non-selective MRA, finerenone is both non-steroidal and selective meaning it is meant to produce greater anti-inflammatory and anti-fibrotic effects whilst avoiding some of the systemic side-effects of spironolactone, such as gynaecomastia. Finerenone has previously been shown to improve cardiovascular and kidney outcomes in people with diabetes and proteinuric chronic kidney disease. 

The FINEARTS-HF trail (it must be nice as a researcher to have a drug with a name that lends itself to catchy study titles!) randomised 6,000 patients who had symptomatic heart failure and a left ventricular ejection fraction ≥40% to receive either finerenone or placebo. The mean age of participants was 72 and 46% were female. Over nearly three year median follow-up, people randomised to finerenone had a 16% relative reduction in the primary outcome of cardiovascular death or worsening heart failure events (rate ratio 0.84, 95%CI 0.74-0.95, p=0.007). The treatment effect was similar irrespective of the left ventricular ejection fraction and was similar in magnitude to that seen in the studies of the SGLT2 inhibitors. 

FINEARTS-HF is the fourth major randomised trial of MRA in people with heart failure and the largest to date. An individual patient data meta-analysis of nearly 14,000 patients within these studies supports the use of spironolactone or eplerenone in people with heart failure and reduced ejection fraction but also finerenone for people with HFpEF, albeit with a smaller treatment effect. 

The bottom line? The trial results are certainly encouraging that finerenone might well play an increasingly important role in the treatment of people with heart failure and/or chronic kidney disease. Currently it is only licensed in the UK for people with proteinuric CKD and type 2 diabetes, but that may well change in light of these recent results. For patients, there is hope that finerenone will prove to be a medicine that can help improve outcomes in HFpEF but also may help with symptom benefit given its diuretic effect. Fine news indeed!