MRAs in heart failure with renal impairment

A common scenario in heart failure (HF) management is a decline in eGFR that occurs with the disease trajectory, commonly resulting in guideline-directed medical therapies either not being initiated or stopped. Recent evidence, however, suggests with mineralocorticoid receptor antagonists that a decline in eGFR is not necessarily a concern.

Mineralocorticoid receptor antagonists (MRAs) are often withheld or discontinued because of renal dysfunction. Investigators hypothesised that, in participants treated with an MRA, a decline in eGFR to <30 mL/min/1.73 m² would occur more often, but this decrease would not compromise the benefits of the therapy or result in an unacceptable safety profile. 

To test this hypothesis, a post hoc analysis of individual patient data pooled from the RALES and EMPHASIS-HF trials was conducted. RALES compared spironolactone and matched placebo in individuals with a left-ventricular ejection fraction (LVEF) ≤35% and severe HF symptoms with an ACE inhibitor (if tolerated) and a loop diuretic. EMPHASIS-HF compared eplerenone and matched placebo in people with LVEF ≤35% and mild HF symptoms with an ACE inhibitor or ARB and a beta-blocker (unless contraindicated).

In the pooled analysis comprising 4355 participants, 2162 of which were randomised to an MRA and 2193 to placebo. In total, a deterioration in eGFR to <30 mL/min/1.73 m² was experienced at least once by 295 (6.8%) participants. These individuals had greater impairment of baseline cardiac and kidney function (eGFR, 47.3±13.4 vs 70.5±21.8 mL/min/1.73 m²). They also had a higher risk of the primary outcome of cardiovascular death or HF hospitalisation than participants without eGFR deterioration (HR, 2.49; 95% CI, 2.01–3.08; P<0.001).

The risk reduction in the primary outcome with an MRA, however, was similar in those who experienced a decrease in eGFR to <30 mL/min/1.73 m² (HR, 0.65; 0.43–0.99) compared with those who did not (HR, 0.63; 0.56–0.71) (P_interaction=0.87). In those with an eGFR decrease to <30 mL/min/1.73 m², 21 fewer individuals (per 100 person-years) experienced the primary outcome with MRA treatment versus placebo, compared with an excess of 3 more participants with severe hyperkalaemia (defined as >6.0 mmol/L).

The authors concluded that while those treated with an MRA are more likely to experience a decline in eGFR to <30 mL/min/1.73 m², the relative efficacy of this therapy is maintained in these people, and the safety profile is similar to that seen in those not experiencing such a decline. As those experiencing a decrease in eGFR to <30 mL/min/1.73 m² are at very high risk, the absolute risk reduction with an MRA in these individuals is large and this decline should not automatically lead to treatment discontinuation.

The full article can be read here.