633 Efficacy of additional medical therapies in patients with heart failure, reduced ejection fraction, and chronic kidney disease already receiving neurohormonal inhibitors: a network meta-analysis

Abstract

Aims: We assessed the efficacy of add-on drugs in patients with heart failure with reduced ejection fraction (HFrEF) and concomitant chronic kidney disease (CKD) already receiving neurohormonal inhibition (NEUi). Methods and results: The literature was systematically searched for phase 3 randomized controlled trials (RCTs) involving ≥90% patients with left ventricular ejection fraction <45%, of whom <30% were acutely decompensated, and with published information about the subgroup of estimated glomerular filtration rate <60 ml/min/ 1.73 m2. Six RCTs were included in a study-level network meta-analysis evaluating the effect of NEUi, ivabradine, angiotensin receptor-neprilysin inhibitor (ARNI), sodium-glucose cotransporter-2 inhibitors (SGLT2i), vericiguat, and omecamtiv mecarbil (OM) on a composite outcome of cardiovascular death or hospitalization for heart failure. In a fixed-effects model, SGLT2i (HR: 0.78, 95% CrI: 0.69-0.89), ARNI (HR: 0.79, 95% CrI: 0.69-0.90), and ivabradine (HR: 0.82, 95% CrI: 0.69-0.98) decreased the risk of the composite outcome vs. NEUi, whereas OM did not (HR: 0.98, 95% CrI: 0.89-1.10). A trend for improved outcome was also found for vericiguat (HR: 0.90, 95% CrI: 0.80-1.00). In indirect comparisons, both SLGT2i (HR: 0.80, 95% CrI: 0.68-0.94) and ARNI (HR: 0.80, 95% CrI: 0.68-0.95) reduced the risk vs. OM; furthermore, there was a trend for a greater benefit of SGLT2i vs. vericiguat (HR: 0.88, 95% CrI: 0.73-1.00) and ivabradine vs. OM (HR: 0.84, 95% CrI: 0.68-1.00). Results were comparable in a random-effects model and in sensitivity analyses. SUCRA scores were 81.8%, 80.8%, 68.9%, 44.2%, 16.6%, and 7.8% for SGLT2i, ARNI, ivabradine, vericiguat, OM, and NEUi, respectively. Conclusions: Expanding pharmacotherapy beyond NEUi improves outcomes in HFrEF with CKD.