MRAs Show Varied Efficacy in Heart Failure Across Ejection Fractions

Sep 27, 2024

Photo Credit: Bluebay2014

A meta-analysis of about 14,000 patients with heart failure (HF) assessed the differential impact of mineralocorticoid receptor antagonists (MRAs) on patients with HF across the spectrum of ejection fractions. The conclusion was that although the evidence was somewhat stronger for patients with reduced ejection fractions, the non-steroidal MRA finerenone also showed efficacy in patients with higher ejection fractions.

While MRAs are well-established in reducing hospitalizations and mortality in HF with reduced ejection fraction (HFrEF), their benefits in HF with mildly reduced (HFmrEF) or preserved ejection fraction (HFpEF) have been less clear. Pardeep Jhund, MD, from University of Glasgow, in Scotland, presented the meta-analysis, which was simultaneously published in the Lancet. The analysis pooled data from four major trials: RALES and EMPHASIS-HF, which focused on HFrEF, TOPCAT, and FINEARTS-HF, which focused on HFmrEF and HFpEF^1-6.

The meta-analysis included 13,846 patients and revealed that MRAs significantly reduced the risk for cardiovascular death or HF hospitalization, with a hazard ratio (HR) of 0.77 (95% CI 0.72–0.83; P<0.001). However, the efficacy varied significantly between the HF subtypes. In patients with HFrEF, MRAs showed greater benefit, reducing the risk by 34% (HR 0.66; 95% CI 0.59–0.73; P<0.001). In contrast, the reduction was more modest in patients with HFmrEF or HFpEF, with a 13% risk reduction (HR 0.87; 95% CI 0.79–0.95; P=0.004).

The analysis also found that MRAs significantly decreased HF hospitalizations as an individual component in both HFrEF (HR 0.63; 95% CI 0.55–0.72; P<0.001) and HFmrEF/HFpEF (HR 0.82; 95% CI 0.74–0.91; P<0.001) populations. Cardiovascular death was reduced in patients with HFrEF (HR 0.72; 95% CI 0.63–0.82; P<0.001), but not in those with HFmrEF or HFpEF (HR 0.92; 95% CI 0.80–1.05; P=0.20). Similarly, all-cause mortality was reduced in HFrEF (HR 0.73; 95% CI 0.65–0.83; P<0.001) but not in patients with HFmrEF or HFpEF (HR 0.94; 95% CI 0.85–1.03; P=0.19).

In terms of safety, the use of MRAs was associated with a doubled risk for hyperkalemia compared with placebo (OR 2.27; 95% CI 2.02–2.56; P<0.001), though the incidence of severe hyperkalemia (serum potassium >6.0 mmol/L) remained low at 2.9% versus 1.4%, and there were no deaths due to hyperkalemia. Interestingly, MRAs also reduced the risk for hypokalemia by half (OR 0.51; 95% CI 0.45–0.57; P<0.001).

These findings suggest that while steroidal MRAs are highly effective in reducing cardiovascular death and hospitalizations in HFrEF, non-steroidal MRAs like finerenone offer similar benefits for patients with HFmrEF or HFpEF, albeit to a lesser extent. This new meta-analysis reinforces the need for tailored treatment approaches depending on the type of HF and ejection fraction at the individual level.