162 Return of the MRA: Comparative Tolerability and Safety of ARNI With MRA Co-Prescription in HFrEF

Abstract

Angiotensin receptor-neprilysin inhibitors (ARNI) and mineralocorticoid receptor antagonists (MRA) are guideline directed medical therapy (GDMT) in managing HF with reduced EF (HFrEF). The perceived risk of hyperkalaemia and reduced renal function with both agents may influence prescribing practices. We sought to determine the tolerability and safety of MRA co-prescription during ARNI initiation and titration. A retrospective single-centre analysis of 265 consecutive HFrEF patients commenced on ARNI between 2016-19 was performed to evaluate tolerability of ARNI and incidence of hyperkalaemia or renal function reduction, with or without MRA co-prescription. Of the 265 patients, 159(60%) were co-prescribed MRA at the time of ARNI initiation. Eleven patients (10%) without MRA had a documented contraindication due to prior hyperkalaemia. Frequency of achieving target dose ARNI (97/103mg BiD) was similarly high among those with MRA (58%) and without MRA (49%). MRA co-prescription was not associated with lower rate of successful ARNI titration (OR 1.5; 95% CI 0.9, 2.5; p=0.12). MRA was ceased in 28(18%) patients during ARNI titration (3 due to hyperkalemia, 4 due to renal impairment). In contrast, 21(20%) patients were commenced on MRA after ARNI initiation. Overall, incidence of hyperkalaemia was comparable (4.5% with MRA; 6.6% without MRA; p=0.45). Reduction in renal function (defined as change in CKD class) was higher among those co-prescribed MRA (19% vs 9.1%; p=0.09). Despite concerns, MRA co-prescription was not associated with increased risk of hyperkalaemia or reduced tolerability of target dose ARNI. MRA underutilization, independent of ARNI tolerability, remains a gap in real-world implementation of GDMT.