Guideline-directed medical therapies (GDMTs) are the mainstay of treatment for heart failure with reduced ejection fraction (HFrEF), but they are underused. Whether sex differences exist in the initiation and intensification of GDMT for newly diagnosed HFrEF is not well established.
Patients with incident HFrEF were identified from the 2016 to 2020 Optum deidentified Clinformatics Data Mart Database, which is derived from a database of administrative health claims for members of large commercial and Medicare Advantage health plans. The primary outcome was the use of optimal GDMT within 12 months of HFrEF diagnosis. Consistent with the guideline recommendations during the time period of the study, optimal GDMT was defined as ≥50% of the target dose of evidence-based beta-blocker plus ≥50% of the target dose of angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, or any dose of angiotensin receptor neprilysin inhibitor plus any dose of mineralocorticoid receptor antagonist. The probability of achieving optimal GDMT on follow-up and predictors of optimal GDMT were evaluated with time-to-event analysis with adjusted Cox proportional hazard models.
The study cohort included 63 759 patients (mean age, 71.3 years; 15.2% non-Hispanic Black race; 56.6% male). Optimal GDMT use was achieved by 6.2% of patients at 12 months after diagnosis. Female (compared with male) patients with HFrEF had lower use across every GDMT class and lower use of optimal GDMT at each time point at follow-up. In an adjusted Cox model, female sex was associated with a 23% lower probability of achieving optimal GDMT after diagnosis (hazard ratio [HR], 0.77 [95% CI, 0.71-0.83]; P<0.001). The sex disparities in GDMT use after HFrEF diagnosis were most pronounced among patients with commercial insurance (females compared with males; HR, 0.66 [95% CI, 0.58-0.76]) compared with Medicare (HR, 0.85 [95% CI, 0.77-0.92]); Pinteraction sex×insurance status=0.005) and for younger patients (age <65 years: HR, 0.65 [95% CI, 0.58-0.74]) compared with older patients (age ≥65 years: HR, 87 [95% CI, 80-96]) Pinteraction sex×age=0.009).
Overall use of optimal GDMT after HFrEF diagnosis was low, with significantly lower use among female (compared with male) patients. These findings highlight the need for implementation efforts directed at improving GDMT initiation and titration.

Despite recent advances in the use of guideline-directed medical therapy (GDMT) for patients with heart failure with reduced ejection fraction (HFrEF), achievement of target GDMT use and up-titration to goal dosages continue to be modest. In recent years, a number of interventional approaches to improve the usage of GDMT have been published, but many are limited by single-center experiences with small sample sizes. However, strategies including the use of multidisciplinary teams, dedicated GDMT titration algorithms and clinician audits with feedback have shown promise. There remains a critical need for large, rigorous trials to assess the utility of differing interventions to improve the use and titration of GDMT in HFrEF. Here, we review existing literature in GDMT implementation for those with HFrEF and discuss future directions and considerations in the field.

OBJECTIVE: Current heart failure (HF) guidelines recommend to prescribe four drug classes in patients with HF with reduced ejection fraction (HFrEF). A clear challenge exists to adequately implement guideline-directed medical therapy (GDMT) regarding the sequencing of drugs and timely reaching target dose. It is largely unknown how the paradigm shift from a serial and sequential approach for drug therapy to early parallel application of the four drug classes will be executed in daily clinical practice, as well as the reason clinicians may not adhere to new guidelines. We present the design and rationale for the real-world TITRATE-HF study, which aims to assess sequencing strategies for GDMT initiation, dose titration patterns (order and speed), intolerance for GDMT, barriers for implementation, and long-term outcomes in patients with de novo, chronic, and worsening HF.
RESULTS: A total of 4000 patients with HFrEF, HF with mildly reduced ejection fraction, and HF with improved ejection fraction will be enrolled in >40 Dutch centres with a follow-up of at least 3 years. Data collection will include demographics, physical examination and vital parameters, electrocardiogram, laboratory measurements, echocardiogram, medication, and quality of life. Detailed information on titration steps will be collected for the four GDMT drug classes. Information will include date, primary reason for change, and potential intolerances. The primary clinical endpoints are HF-related hospitalizations, HF-related urgent visits with a need for intravenous diuretics, all-cause mortality, and cardiovascular mortality.
CONCLUSIONS: TITRATE-HF is a real-world multicentre longitudinal registry that will provide unique information on contemporary GDMT implementation, sequencing strategies (order and speed), and prognosis in de novo, worsening, and chronic HF patients.

Heart failure (HF) is a significant event for public health. It has a prevalence between 1-2%, mortality rate between 7-17%, and hospitalization between 32-44%. This implies a risk to health and quality of life, but also great financial efforts for health systems. Sacubitril/valsartan is a medication recognized for its efficacy, and this consensus seeks to synthesize the available information regarding its use for the benefit of patients. This document consists of a description of the epidemiology of HF, pharmacology of the drug, clinical trials, use of the drug in cases with reduced ejection fraction, mildly reduced ejection fraction and preserved ejection fraction, available literature on HF guidelines, recommendations and conclusions.
La insuficiencia cardiaca (IC) es un evento significativo para la salud pública. Tiene una prevalencia entre el 1 y 2%, tasa de mortalidad entre el 7 y 17% y de hospitalización entre el 32 y 44%. Esto implica un riesgo a la salud y calidad de vida, pero también grandes esfuerzos financieros para los sistemas de salud. El sacubitrilo/valsartán es un medicamento reconocido por su eficacia, y este consenso busca sintetizar la información disponible respecto a su uso en búsqueda del beneficio de los pacientes. El presente documento se compone de una descripción de la epidemiología de la IC, farmacología del medicamento, estudios clínicos sobre este, uso del medicamento en casos con fracción de eyección reducida, fracción de eyección ligeramente reducida y fracción de eyección preservada, literatura disponible en guías de IC, recomendaciones y conclusiones.

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Despite the availability of lifesaving guideline-directed medical therapy (GDMT) for heart failure with reduced ejection fraction (HFrEF), there remain major gaps in utilization of these therapies among eligible patients. Simultaneous with these gaps in quality of care, HFrEF continues as a leading cause of death and hospitalization with associated clinical risk far exceeding most other cardiovascular and noncardiovascular conditions. In the context of this urgent need to improve provision of appropriate therapy, multiple lines of evidence support various implementation strategies. Such strategies include in-hospital initiation of GDMT, simultaneous or rapid sequence initiation of GDMT, participation in quality improvement registries to assess site performance and provide feedback, multidisciplinary titration clinics, virtual consult teams, reduction of cost-sharing, remote algorithm-based medication optimization, electronic health record-based interventions, and direct-to-patient educational initiatives. This review describes and contextualizes the evidence surrounding each of these potential avenues for improving use of foundational GDMTs for patients with HFrEF.

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We investigated the eligibility for vericiguat in a real-world heart failure (HF) population based on trial, guideline and label criteria.
From the Swedish HF registry, 23 573 patients with HF with reduced ejection fraction (HFrEF) enrolled between 2000 and 2018, with a HF duration ≥6 months, were considered. Eligibility for vericiguat was calculated based on criteria from (i) the Vericiguat Global Study in Subjects with Heart Failure and Reduced Ejection Fraction (VICTORIA) trial; (ii) European and American guidelines on HF; (iii) product labelling according to the Food and Drug Administration and European Medicines Agency. Estimated eligibility for vericiguat in the trial, guidelines, and label scenarios was 21.4%, 47.4%, and 47.4%, respectively. Prior HF hospitalization within 6 months was the criterion limiting eligibility the most in all scenarios (met by 49.1% of the population). In the trial scenario, other criteria meaningfully limiting eligibility were elevated N-terminal pro-B-type natriuretic peptide levels and nitrate use. In all scenarios, eligibility was higher among patients hospitalized for HF at baseline (44.3% vs. 21.4% [trial scenario] and 97.3% vs. 47.4% [guideline/label scenarios] for hospitalized vs. non-hospitalized patients). Overall, eligible patients were older, had more severe HF, more comorbidities, and consequently higher cardiovascular mortality and HF hospitalization rates compared with ineligible patients across all scenarios.
In a large and contemporary real-world HFrEF cohort, we estimated that 21.4% of patients would be eligible for vericiguat according to the VICTORIA trial selection criteria, 47.4% based on guidelines and labelling. Eligibility for vericiguat translated into the selection of a population at high risk of morbidity/mortality.

Clinical guidelines for patients with heart failure with reduced ejection fraction (HFrEF) strongly recommend treatment with a sodium-glucose cotransporter-2 inhibitor (SGLT2i) to reduce cardiovascular mortality or HF hospitalization. Nationwide adoption of SGLT2i for HFrEF in the US is unknown.
To characterize patterns of SGLT2i use among eligible US patients hospitalized for HFrEF.
This retrospective cohort study analyzed 49 399 patients hospitalized for HFrEF across 489 sites in the Get With The Guidelines-Heart Failure (GWTG-HF) registry between July 1, 2021, and June 30, 2022. Patients with an estimated glomerular filtration rate less than 20 mL/min/1.73 m2, type 1 diabetes, and previous intolerance to SGLT2i were excluded.
Patient-level and hospital-level prescription of SGLT2i at hospital discharge.
Of 49 399 included patients, 16 548 (33.5%) were female, and the median (IQR) age was 67 (56-78) years. Overall, 9988 patients (20.2%) were prescribed an SGLT2i. SGLT2i prescription was less likely among patients with chronic kidney disease (CKD; 4550 of 24 437 [18.6%] vs 5438 of 24 962 [21.8%]; P < .001) but more likely among patients with type 2 diabetes (T2D; 5721 of 21 830 [26.2%] vs 4262 of 27 545 [15.5%]; P < .001) and those with both T2D and CKD (2905 of 12 236 [23.7%] vs 7078 vs 37 139 [19.1%]; P < .001). Patients prescribed SGLT2i therapy were more likely to be prescribed background triple therapy with an angiotensin-converting enzyme inhibitor/angiotensin receptor blocker/angiotensin receptor-neprilysin inhibitor, β-blocker, and mineralocorticoid receptor antagonist (4624 of 9988 [46.3%] vs 10 880 of 39 411 [27.6%]; P < .001), and 4624 of 49 399 total study patients (9.4%) were discharged with prescriptions for quadruple medical therapy including SGLT2i. Among 461 hospitals with 10 or more eligible discharges, 19 hospitals (4.1%) discharged 50% or more of patients with prescriptions for SGLT2i, whereas 344 hospitals (74.6%) discharged less than 25% of patients with prescriptions for SGLT2i (including 29 [6.3%] that discharged zero patients with SGLT2i prescriptions). There was high between-hospital variance in the rate of SGLT2i prescription in unadjusted models (median odds ratio, 2.53; 95% CI, 2.36-2.74) and after adjustment for patient and hospital characteristics (median odds ratio, 2.51; 95% CI, 2.34-2.71).
In this study, prescription of SGLT2i at hospital discharge among eligible patients with HFrEF was low, including among patients with comorbid CKD and T2D who have multiple indications for therapy, with substantial variation among US hospitals. Further efforts are needed to overcome implementation barriers and improve use of SGLT2i among patients with HFrEF.

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