Aug 2026· JACC. Heart failure· pp.
103295
· 1 citation· 39 references
Medicine
TL;DR
Incomplete implementation of quadruple GDMT in HFrEF remains a major modifiable opportunity to reduce preventable deaths and HF hospitalizations in the United States.
Abstract
Background
Despite robust evidence that quadruple guideline-directed medical therapy (GDMT), comprising angiotensin receptor-neprilysin inhibitors (ARNIs), evidence-based beta-blockers, mineralocorticoid receptor antagonists (MRAs), and sodium-glucose cotransporter 2 (SGLT2) inhibitors, reduces mortality and hospitalizations in heart failure with reduced ejection fraction (HFrEF), implementation in clinical practice remains markedly incomplete.
Objectives
This study aimed to provide updated national estimates of the eligible untreated HFrEF population and to quantify deaths and hospitalizations preventable with optimal implementation of quadruple GDMT in the United States.
Methods
The authors performed a population-level decision analytic modeling study using contemporary U.S. epidemiologic data. National HFrEF prevalence estimates were derived from the American Heart Association Heart Disease and Stroke Statistics 2026 report, and annual HFrEF hospitalization counts were derived from the National Inpatient Sample 2022-2023. Eligible untreated populations were estimated after sequential exclusions and therapy-specific contraindication adjustments using primary treatment rates from Epic Cosmos 2023-2025, with sensitivity analyses using alternative treatment-rate sources. Trial-derived numbers needed to treat and relative risk reductions were applied to estimate deaths preventable over 12 months and annual heart failure (HF) hospitalizations prevented.
Results
An estimated 2.76 million U.S. adults with chronic symptomatic HFrEF were eligible for quadruple GDMT, yet only 18.2% received it. Eligible untreated populations included 733,891 for beta-blockers, 1,856,531 for ARNIs, 1,543,967 for MRAs, and 1,717,444 for SGLT2 inhibitors. Class-specific projected deaths preventable over 12 months were 26,210 for beta-blockers, 34,495 for ARNIs, 26,620 for MRAs, and 26,422 for SGLT2 inhibitors; the aggregate estimate across treatment gaps was 113,747 (95% uncertainty interval [UI]: 90,173-149,875). Optimal implementation was also projected to prevent 357,332 HF hospitalizations annually (95% UI: 297,493-425,674).
Conclusions
Incomplete implementation of quadruple GDMT in HFrEF remains a major modifiable opportunity to reduce preventable deaths and HF hospitalizations in the United States.
Although ACEI/ARB/ARNI therapy showed high adherence, BBs and MRAs were less frequently used, and SGLT2Is were under-prescribed, greater efforts are needed to improve adherence to ESC recommendations at discharge.
Andrijana Stošić, Marija Polovina· Medicinski Podmladak· 0 citations
Guideline-directed medical therapy (GDMT) improves outcomes in heart failure with reduced ejection fraction (HFrEF). However, implementation remains suboptimal, and evidence for inpatient pharmacist-led interventions is limited. We evaluated the association between a pharmacist-led electronic medical record (EMR)-embedded checklist and GDMT use in hospitalized patients with acute heart failure.
A single-center, retrospective, non-randomized study with a historical control group was conducted. Adult patients hospitalized with acute heart failure from October 2021 to March 2023 were enrolled. Patients admitted between October 2022 and March 2023 formed the pharmacist-led GDMT checklist intervention group, whereas those admitted between October 2021 and March 2022 served as historical controls. Primary outcomes were discharge implementation and new initiation rates of individual GDMT agents (renin–angiotensin system inhibitors, beta-blockers, mineralocorticoid receptor antagonists [MRA], sodium–glucose cotransporter-2 inhibitors [SGLT2i]) and quadruple therapy. Exploratory multivariable logistic regression was performed for quadruple therapy use at discharge in patients with HFrEF. Secondary outcomes included target-dose achievement, exploratory 90-day heart failure readmission, and all-cause mortality.
A total of 103 patients were included (49 controls, 54 intervention). Among patients with HFrEF (22 controls, 23 intervention), the intervention group had higher prescription rates of MRA (87.0% vs. 59.1%,
p
= 0.047) and SGLT2i (95.7% vs. 72.7%,
p
= 0.047). Quadruple therapy was achieved in 78.3% vs. 40.9% (
p
= 0.016). The proportion of patients who newly achieved quadruple therapy during hospitalization was also higher in the intervention group (83.3% vs. 35.0%,
p
= 0.038). In the exploratory multivariable model, the intervention remained associated with higher odds of quadruple therapy use at discharge. Target-dose achievement was similar between groups. In mildly reduced/preserved EF, discharge SGLT2i use tended to be higher in the intervention group (
p
= 0.062). Exploratory 90-day outcomes showed no clear between-group differences and were limited by incomplete follow-up and insufficient statistical power.
The pharmacist-led EMR-embedded checklist intervention was associated with higher discharge implementation and in-hospital initiation of HFrEF-directed GDMT, particularly MRA, SGLT2i, and quadruple therapy. This simple checklist-based approach may support evidence-based pharmacotherapy optimization and warrants confirmation in larger multicenter studies with long-term follow-up.
Hikaru Katagiri, Komei Tanaka, Ryuji Kobayashi et al.· Journal of Pharmaceutical He...· 0 citations
Abstract Objective To evaluate the clinical effectiveness of sodium glucose cotransporter 2 (SGLT2) inhibitors in reducing the risk of hospital admission for heart failure and mortality in a contemporary nationwide cohort of patients with heart failure with preserved ejection fraction (HFpEF). Design Nationwide cohort study (REFINE-HFpEF). Setting 170 veteran health medical centres across the US, 1 January 2014 to 31 December 2021. Participants 2177 patients with type 2 diabetes and HFpEF; 1129 patients were newly prescribed SGLT2 inhibitors and 1048 were newly prescribed dipeptidyl peptidase 4 (DPP4) inhibitors or sulfonylureas. Main outcome measures The primary outcome was a composite of all cause mortality and hospital admission for heart failure. Secondary outcomes included all cause mortality only and serial changes in body weight. Hazard ratios were derived from Cox proportional hazards models, incorporating inverse probability of treatment weighting based on propensity scores to account for confounding. Results From a validated cohort of 179 288 patients with type 2 diabetes and HFpEF, the study included 1129 new users of SGLT2 inhibitors (active treatment) and 1048 new users of DPP4 inhibitors or sulfonylureas (comparators). After a median follow-up of 2.63 years, 46.4% of the study population had at least one hospital admission for heart failure (n=1011) and the overall mortality rate was 45.9% (n=1000). Use of SGLT2 inhibitors was associated with a relative risk reduction in the primary composite outcome of 18% compared with the use of DPP4 inhibitors or sulfonylureas (hazard ratio 0.82, 95% confidence interval 0.70 to 0.96; P=0.01). The adjusted hazard ratio for all cause mortality only was 0.73 (0.60 to 0.89; P=0.002). Weight loss was similar in the two groups. Conclusions In this large, contemporary, nationwide cohort of patients with HFpEF, type 2 diabetes, and high event rates, starting SGLT2 inhibitors was associated with a significantly lower risk of hospital admission for heart failure and all cause mortality compared with starting treatment with DPP4 inhibitors or sulfonylureas.
BACKGROUND
Despite strong evidence, adoption of guideline-directed medical therapy (GDMT) for heart failure with reduced ejection fraction remains suboptimal. The Get With The Guidelines-Heart Failure (GWTG-HF) program was designed to close gaps in care. We evaluated whether hospital participation in GWTG-HF was associated with greater GDMT intensity and improved outcomes.
METHODS
We conducted a retrospective analysis (2013-2021) of Medicare beneficiaries with part A and part D hospitalized with heart failure with reduced ejection fraction. Using a multiple baseline time series design, we compared changes in GDMT and outcomes before and after GWTG-HF enrollment with hospitals that never participated. Coprimary outcomes were a 90-day postdischarge GDMT score under a parallel and nonparallel slopes model. Secondary outcomes included class-specific medication fills, achievement of ≥50% target doses, and 30-day, 90-day, and 1-year all-cause and HF readmission and mortality. Mortality and first HF readmission were also evaluated using Cox proportional hazards models. We adjusted for baseline hospital performance, patient characteristics, and temporal trends.
RESULTS
Among 1274 863 Medicare beneficiaries hospitalized for heart failure with reduced ejection fraction, 53.5% were treated at hospitals that never participated in GWTG-HF and 9.6% at GWTG-HF hospitals. Unadjusted median GDMT scores increased from 3.0 in both groups to 4.0 in nonparticipating hospitals and 4.5 in GWTG-HF hospitals at 90 days (P<0.001). Hospital enrollment was associated with a higher 90-day GDMT score (+0.15 points [95% CI, 0.12-0.20]; P<0.001) and greater use of β-blockers, renin-angiotensin system inhibitors, and mineralocorticoid receptor antagonists but not angiotensin receptor-neprilysin inhibitors. GWTG-HF participation was associated with lower all-cause mortality at 30 days (odds ratio, 0.95 [95% CI, 0.92-0.98]) and 1 year (0.97 [95% CI, 0.95-0.1.00]; both P<0.05). Mortality differences were attenuated and no longer significant in the nonparallel slopes model.
CONCLUSIONS
Hospital participation in GWTG-HF was associated with modest but significant improvements in postdischarge GDMT intensity, supporting the value of quality improvement initiatives to address persistent treatment gaps in heart failure with reduced ejection fraction.
Aradhana Verma, Greg C. Fonarow, Paul A. Heidenreich et al.· Circulation: Heart Failure· 0 citations
OBJECTIVE
To investigate the impact of the 2021 guideline update on guideline-directed medical therapy (GDMT) utilization in patients with heart failure (HF).
BACKGROUND
The 2021 update of the Japanese guidelines for HF management followed the introduction of sacubitril/valsartan and dapagliflozin into clinical practice. However, the impact of this guideline update on drug utilization patterns remains unclear.
MATERIALS AND METHODS
Patient data were obtained from the Japanese employee health insurance claims database (JMDC). The simple GDMT score was determined based on the combination and dose of four key pharmacological classes: β-blockers, renin-angiotensin system inhibitors, mineralocorticoid receptor antagonists, and sodium-glucose cotransporter 2 inhibitors. Because a simple GDMT score of ≥ 5 has been associated with improved prognosis in patients with HF, patients with scores ≥ 5 were classified into the high-score group for analysis.
RESULTS
Following the guideline update, the proportion of patients in the high-score group increased from 6.97% (n = 4,013) to 9.33% (n = 6,363), standardized difference 0.09. The mean simple GDMT score also showed a small but statistically significant increase (5.72 ± 0.79 vs. 6.00 ± 1.09) with standardized difference 0.28. This upward trend was particularly marked for the prescription rates of sacubitril/valsartan and dapagliflozin (sacubitril/valsartan: 1.40% before the update vs. 22.57% after the update; standardized difference, 0.69; dapagliflozin: 12.41% before the update vs. 26.64% after the update; standardized difference, 0.36).
CONCLUSION
The 2021 guideline update was associated with increased use of sacubitril/valsartan and dapagliflozin, resulting in greater overall GDMT intensity. However, these findings are limited to data from 2021, and further long-term studies are needed to evaluate trends in GDMT utilization.
T. Uno, K. Hosomi, S. Yokoyama· International journal of cli...· 0 citations
BACKGROUND AND AIMS
It is uncertain whether the effect of vericiguat varies across levels of background guideline-directed medical therapy (GDMT) in heart failure with reduced ejection fraction (HFrEF).
METHODS
We conducted an exploratory analysis of VICTOR, which enrolled 6105 ambulatory patients with HFrEF without recent worsening. GDMT exposure was classified as basic adherence (on vs. off), indication-corrected adherence (accounting for eligibility and contraindications), and dose-corrected adherence (≥50% target dose). A GDMT intensity score was computed from class-specific dose levels. The primary endpoint was the composite of cardiovascular death or first HF hospitalization. Stratified Cox proportional hazards regression models estimated adjusted hazard ratios for vericiguat versus placebo within GDMT strata, with treatment-by-GDMT interaction test.
RESULTS
Baseline contemporary GDMT use was high (any ARNI/ACE/ARB 93.9%, ARNI 56%, SGLT2i 59%, MRA 78%, beta-blocker 94%). Basic adherence: adjusted HRs for the primary endpoint were similar whether or not patients were on ACEi/ARB, ARNI, any RAS inhibitor, beta-blocker, or SGLT2i. Dose-corrected adherence: adjusted HRs favored vericiguat in ARNI target-dose users (0.73; 0.57-0.93) and in any RAS target-dose users (0.77; 0.64-0.93), with lower risk on vericiguat in patients not meeting MRA target dose (0.67; 0.48-0.95); interaction P-values were nominally significant. The GDMT intensity score showed no significant interaction with treatment. Patterns for cardiovascular death and all-cause death paralleled the primary endpoint.
CONCLUSIONS
In ambulatory patients with HFrEF receiving contemporary GDMT, we did not find convincing evidence that the neutral effect of vericiguat on cardiovascular death or first HF hospitalization was modified by GDMT class, dose attainment, or overall intensity, in a cohort with very high background GDMT use and limited power for interaction testing. These exploratory, hypothesis-generating findings do not establish independent efficacy or pathway additivity for vericiguat and should not be used to guide clinical recommendations regarding GDMT sequencing.
Justin A. Ezekowitz, J. Butler, Derek Cyr et al.· European Journal of Heart Fa...· 0 citations
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