Aims: We assessed the efficacy of the drugs developed after neurohormonal inhibitors (NEUi) in patients with heart failure with reduced ejection fraction (HFrEF) and concomitant chronic kidney disease (CKD). 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/1.73m2. 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. Conclusion: Expanding pharmacotherapy beyond NEUi improves outcomes in HFrEF with CKD.

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

Ameri, Pietro;De Marzo, Vincenzo;Canepa, Marco;Porto, Italo
2021

Abstract

Aims: We assessed the efficacy of the drugs developed after neurohormonal inhibitors (NEUi) in patients with heart failure with reduced ejection fraction (HFrEF) and concomitant chronic kidney disease (CKD). 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/1.73m2. 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. Conclusion: Expanding pharmacotherapy beyond NEUi improves outcomes in HFrEF with CKD.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11567/1066373
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