Guideline‐directed medical therapy in severe heart failure with reduced ejection fraction: An analysis from the HELP‐HF registry

Aim Persistent symptoms despite guideline‐directed medical therapy (GDMT) and poor tolerance of GDMT are hallmarks of patients with advanced heart failure (HF) with reduced ejection fraction (HFrEF). However, real‐world data on GDMT use, dose, and prognostic implications are lacking. Methods and results We included 699 consecutive patients with HFrEF and at least one ‘I NEED HELP’ marker for advanced HF enrolled in a multicentre registry. Beta‐blockers (BB) were administered to 574 (82%) patients, angiotensin‐converting enzyme inhibitors, angiotensin receptor blockers or angiotensin receptor–neprilysin inhibitors (ACEi/ARB/ARNI) were administered to 381 (55%) patients and 416 (60%) received mineralocorticoid receptor antagonists (MRA). Overall, ≥50% of target doses were reached in 41%, 22%, and 56% of the patients on BB, ACEi/ARB/ARNI and MRA, respectively. Hypotension, bradycardia, kidney dysfunction and hyperkalaemia were the main causes of underprescription and/or underdosing, but up to a half of the patients did not receive target doses for unknown causes (51%, 41%, and 55% for BB, ACEi/ARB/ARNI and MRA, respectively). The proportions of patients receiving BB and ACEi/ARB/ARNI were lower among those fulfilling the 2018 HFA‐ESC criteria for advanced HF. Treatment with BB and ACEi/ARB/ARNI were associated with a lower risk of death or HF hospitalizations (adjusted hazard ratio [HR] 0.63, 95% confidence interval [CI] 0.48–0.84, and HR 0.74, 95% CI 0.58–0.95, respectively). Conclusions In a large, real‐world, contemporary cohort of patients with severe HFrEF, with at least one marker for advanced HF, prescription and uptitration of GDMT remained limited. A significant proportion of patients were undertreated due to unknown reasons suggesting a potential role of clinical inertia either by the prescribing healthcare professional or by the patient. Treatment with BB and ACEi/ARB/ARNI was associated with lower mortality/morbidity. Rates of guideline‐directed medical therapy (GDMT) prescription in real‐world patients with severe heart failure (HF) with reduced ejection fraction (HFrEF), reasons for underdosing and association with outcome. Upper left panel: rates of GDMT prescription and dosing, including beta‐blockers, angiotensin‐converting enzyme inhibitors/angiotensin receptor blockers/angiotensin receptor neprilysin inhibitors (ACEi/ARB/ARNI) and mineralocorticoid receptor antagonists (MRA). Upper right panel: reasons for underdosing of beta‐blockers, ACEi