The uptake and optimization of guideline-directed medical therapy (GDMT) for heart failure with reduced ejection fraction (HFrEF) remain poor in Singapore, owing to underprescription, inadequate dosing, and medication discontinuation, according to a retrospective study.
“Currently, four medication classes—ACE inhibitor (ACEi)/angiotensin II receptor blocker (ARB)/angiotensin receptor-neprilysin inhibitor (ARNI), β-blocker, mineralocorticoid receptor antagonist (MRA) and sodium-glucose cotransporter-2 (SGLT2) inhibitor—are recommended as part of standard HFrEF treatment, commonly referred to as ‘quadruple therapy’,” the authors said.
“Implementing quadruple GDMT at optimal doses has been estimated to reduce 12-month mortality by approximately 10 percent. Global projections suggest that full implementation of quadruple therapy could potentially prevent up to 1.2 million deaths over 12 months, with the highest impact observed in regions such as Southeast Asia, the Eastern Mediterranean, Africa, and the Western Pacific,” they added. [JAMA Cardiol 2024;9:1154-1158]
In Singapore, among 3,999 adults (median age 70 years, 71 percent male, 65 percent Chinese) hospitalized between 2020 and 2022 for a first heart failure and left ventricular ejection fraction ≤40 percent, only 29 percent received quadruple therapy at discharge even though between 80 percent and 99 percent of them met the criteria for each GDMT drug class. [BMJ Open 2026;16:e107127]
Moreover, most patients who were discharged on quadruple therapy received suboptimal drug doses. More than 90 percent of patients were prescribed ACEi/ARB/ARNI and beta-blockers at doses ≤50 percent of the guideline-recommended target dosage. However, dose uptitration slightly improved at the 6-month follow-up, with the percentage of patients receiving more than 50 percent of the target dosage increasing by 3 percent for both drug classes. In contrast, SGLT2 inhibitors were consistently prescribed at optimal doses, with nearly 100 percent of patients receiving more than 75 percent of the guideline-recommended target dosage both at discharge and at 6-month follow-up.
Prescription rates at the 6-month follow-up declined by 16 percent for ACEi/ARB/ARNI, 26 percent for beta-blockers, and 7 percent for MRAs. Conversely, more patients were on SGLT2 inhibitors at 6 months relative to discharge, “suggesting that more patients were initiated on this therapy postdischarge,” the authors noted.
“As a result, quadruple therapy usage slightly increased at 6 months, reflecting a delayed but improving uptake of comprehensive GDMT,” they said.
When analysed individually, prescription rates for all four drug classes remained suboptimal: 67 percent vs 99 percent eligible for ACEi/ARB/ARNI, 89 percent vs 95 percent eligible for beta-blockers, 40 percent vs 100 percent eligible for MRAs, and 46 percent vs 88 percent eligible for SGLT2 inhibitors.
The odds of receiving quadruple therapy were lower among older patients (odds ratio [OR], 0.97, 95 percent confidence interval [CI], 0.96–0.98) and those with higher chronic kidney disease stage (3a: OR, 0.65, 95 percent CI, 0.51–0.82; 3B: OR, 0.31, 95 percent CI, 0.23–0.41; 4: OR, 0.04, 95 percent CI, 0.01–0.08). Meanwhile, males were more likely to receive quadruple therapy than females (OR, 1.51, 95 percent CI, 1.22–1.89), as did patients with certain comorbidities (diabetes: OR, 1.81, 95 percent CI, 1.47–2.22; hypercholesterolaemia: OR, 2.19, 95 percent CI, 1.71–2.85; coronary artery disease: OR, 1.60, 95 percent CI, 1.26–2.04).
“The persistent treatment gap in GDMT for HFrEF in Singapore can be attributed to a combination of physician-, patient- and system-level factors that influence initial prescribing and long-term adherence,” the authors noted.
Physician-related barriers include clinical inertia, guideline misconceptions, prescribing assumptions and unfamiliarity with newer therapies. Patient comorbidities also lead to cautious prescribing despite the absence of contraindications. Lastly, while cost and formulary restrictions have historically played a role in limiting GDMT adoption, the transition from hospital to outpatient care represents a major challenge, given that this is the period where frequent dose titrations and monitoring are required, the authors explained.
“Structured postdischarge programmes, clinician education, financial support for newer therapies, and qualitative research might help refine strategies to enhance GDMT integration into routine care, ultimately improving patient outcomes and HF management,” they said.