Heart failure (HF) refers to a condition of circulatory disorders caused by the inability of the heart to adequately pump venous blood due to impaired systolic and/or diastolic function, thereby resulting in venous congestion and insufficient arterial perfusion (Rogers and Bush, 2015). HF is characterized by symptoms such as shortness of breath, ankle swelling, and fatigue, alongside signs like elevated jugular venous pressure, pulmonary crackles, and peripheral edema (Metra and John R, 2017). As a rapidly progressing public health concern, it is estimated that there are currently over 64.3 million HF patients, and its prevalence continues to be on the rise (Savarese et al., 2023). The 30-day readmission rate of HF is as high as 20%–25% (Groenewegen et al., 2020). Furthermore, in 2012, the annual global healthcare costs for HF were over $108 billion and are expected to increase to $210 billion by 2030, thus creating a significant economic burden on society (Savarese et al., 2023). Extensive data also showed that each hospitalization decreases a patient’s health-related quality of life (HRQoL) and increases both 6-month and 1-year mortality rates (Setoguchi et al., 2007; Keidan et al., 2019).

Guideline-directed medical therapy (GDMT) refers to the standardized pharmacological treatment for specific diseases, particularly chronic conditions, based on recommendations from authoritative clinical guidelines and evidence from large-scale randomized clinical trials (Van der Meer et al., 2019). With objectives to improve survival rates, prevent recurrent hospitalizations, and enhance functional capacity, GDMT serves as the cornerstone of drug therapy for heart failure patients (Patel et al., 2023). According to “2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure” (Ponikowski et al., 2016) and “2018 Chinese Guidelines for the Diagnosis and Treatment of Heart Failure” (Liang, 2018), GDMT primarily includes five medication classes: diuretics, angiotensin receptor-neprilysin inhibitors (ARNI)/renin-angiotensin system inhibitors (ACEI/ARB), Beta-blockers, mineralocorticoid receptor antagonists (MRA), and sodium-glucose cotransporter-2 inhibitors (SGLT-2i). Therefore, one of the objectives of this study was to statistically analyze current medication usage among HF patients and identify existing treatment issues to promote GDMT implementation, ultimately improving patient outcomes and reducing disease burden.

In clinical practice, HF can be classified as heart failure with reduced ejection fraction (HFrEF, LVEF <40%), heart failure with mildly reduced ejection fraction (HFmrEF, 40% ≤LVEF <50%), and heart failure with preserved ejection fraction (HFpEF, LVEF ≥50%) (Lips and Cerny, 2022). Over time, pharmacological treatment for HF has evolved from a traditional approach focused on “positive inotropes, diuretics, and vasodilators” to the “triple-drug regimen” (ACEI/ARB + Beta-blockers + MRAs), and more recently, to novel HF medications, such as ARNIs and SGLT-2i. Currently, the pharmacological treatment for HFrEF primarily includes ACEIs, Beta-blockers, MRAs, and SGLT-2i, which have been shown to significantly improve patient prognosis (Rossignol et al., 2019). Previous studies have demonstrated that, compared to traditional therapies, a comprehensive approach combining multiple pharmacologic strategies can reduce cardiovascular hospitalization and mortality rates (Lim, 2020). Most medications that are effective for HFrEF do not demonstrate significant efficacy for HFpEF (Rossignol et al., 2019). Although some mediators of HFpEF are considered promising targets for pharmacological treatment, currently only the EMPEROR-Preserve randomized trial of empagliflozin has demonstrated the ability to reduce cardiovascular hospitalization and mortality rates in HFpEF patients (Packer et al., 2021). Additionally, there is a notable lack of prospective studies on HFmrEF. Thus, GDMT is critical for improving clinical outcomes in HF patients. Conversely, the absence of GDMT may lead to rapid disease progression and complications. Therefore, the other objectives of this study were to assess the relationship between different types of HF, the use of various medications, and readmission rates, thereby providing insights and evidence for clinical decision-making and promoting rational medication practices.

With the current advances in scientific research, HF management has evolved from the initial approaches of cardiotonic agents, diuretics and vasodilators, the triple therapy (ACEI/ARB + Beta-blockers + MRA) and now to the quadruple therapy (ACEI/ARB/ARNI + Beta-blockers + MRA + SGLT-2i), thus continuously improving the prognosis of HF (JoAnn et al., 2010; McMurray, 2013; Lips and Cerny, 2022). Moreover, recent data has indicated that the novel quadruple therapy has significant benefits on HF outcomes (Gwag et al., 2018; Lund et al., 2018). The 2014 PARADIGM-HF study showed that, compared to standard treatment (Rogers and Bush, 2015), replacing ACEI with sacubitril/valsartan in HFrEF patients lowered the risk of cardiovascular death and HF hospitalization by 20% and reduced all-cause mortality by 16%. Consequently, ARNI is now preferred over ACEI/ARB in HFrEF pharmacotherapy (Ostios Garcia, 2015). The data obtained in the current study has shown that ANRI has gradually replaced ACEI in HF treatment. However, in the current study, guideline-recommended Beta-blockers did not significantly improve HFrEF prognosis, which was likely due to dosages not reaching the recommended treatment levels. In addition, in some studies, it was indicated that ACEI/ARB, Beta-blockers, and MRA medications may benefit HFmrEF patients by potentially improving their prognosis. HFmrEF patients frequently have comorbid hypertension and coronary artery disease, making ACEI/ARB and Beta-blockers therapies appropriate for managing these conditions (Cleland et al., 2018). The recently completed EMPEROR-Preserved study reported that empagliflozin, compared with the placebo, reduced the risk of cardiovascular death or HF hospitalization by 21% and significantly, early, and consistently lowered the risk and severity of both hospitalization and outpatient HF events in HFpEF patients (Nassif et al., 2021). In our study, patients who received SGLT-2i therapy also demonstrated improved prognosis.

Pharmacists play a significant role in GDMT. They assist doctors in selecting appropriate medications, adjusting dosages, and evaluating drug interactions based on the recommendations of the latest guidelines, while also considering the characteristics of individual patients. Additionally, when contraindications exist, they recommend suitable alternative medications as per the guidelines. Guidance on medication use and lifestyle habits for patients also enhances treatment adherence. This approach enhances treatment quality and ensures safety and effectiveness. In addition, variations in medication usage are influenced by multiple factors, including regional healthcare levels, awareness of HF and its treatment regimen, patient adherence to treatment, and economic conditions. As mentioned earlier, there are also notable differences in HF medication use across departments within our hospital. The data obtained in our study also revealed that guideline-recommended medication usage in our hospital was lower than the national average, with particularly low use rates of triple and new quadruple therapies. Compared to the U.S. GWTG-HF study (Figueroa et al., 2020), the MRA usage from patients in our hospital was higher, but ACEI/ARB/ARNI and BB use rates were lower. This may be because MRA drugs are also frequently used to improve short-term HF severity and, in our setting, may act as diuretics. In recent years, the utilization rate of guideline-recommended medications has been increasing annually, with a significant rise after 2018. This trend may be attributed to the establishment of heart failure centers and the participation of pharmacists in clinical decision-making, which have promoted the implementation of GDMT and are of great significance for improving HF outcomes.

In this study, the 30-day readmission rate for HF patients discharged from our hospital was 5.2%, and increased to 10.1% within 90 days. This increase may relate to suboptimal dosing or inconsistent medication use, which is especially the case for newer HF drugs such as ARNIs and SGLT-2i, which are underutilized. The results obtained from analyzing the relationship between various medications and readmission rates do not fully align with previously reported study findings (Bozkurt, 2024). For example, diuretics, ACEIs, and positive inotropic drugs not only failed to improve patient prognosis but were also associated with higher readmission rates, thus diverging from guideline recommendations and clinical expectations. This discrepancy may result from the retrospective nature of the current study, in which only data from HF patients in our hospital between January 2016 and June 2021 were collected. The data used for this study may have missing information and potential bias, as well as a single-center approach in which only readmissions to our hospital were tracked, and data on patients readmitted elsewhere were not taken into account-our study’s largest limitation. Nonetheless, most findings align with data presented in the existing literature. Based on our findings, newer anti-HF drugs such as ARNIs and SGLT-2i, along with triple and quadruple therapy regimens were shown to effectively improve patient outcomes, thereby offering greater options and evidence for optimizing clinical treatment of HF. Early, low-dose use of new quadruple therapy (ARNI/ACEI/ARB + Beta-blockers + MRA + SGLT-2i), with gradual titration to target or maximally tolerated doses and long-term maintenance, may provide an effective strategy for significantly reducing readmission and mortality rates and improving HF prognosis (Rossignol et al., 2019).

The strength of this study lies in its large sample size (n = 5356), including accurate, reliable data that covers a diverse population, thus ensuring a degree of representativeness. However, as a retrospective study, this study is affected by missing data and potential bias and therefore, there is a certain time lag in the findings. Additionally, the single-center date is another limitation of this study. Nevertheless, this study assesses the real-world impact of various drugs on HF prognosis, thereby providing significant guidance for clinical drug selection. Future plans involve a large-scale, multicenter, prospective clinical study to validate the findings and to more accurately assess the impact of different drugs on HF prognosis.

Cardiovascular disease has become the leading cause of death in China, with the incidence of HF increasing rapidly. The mortality rate of HF, comparable to that of cancer, makes it a significant public health concern both domestically and globally. Currently, the utilization rate of guideline-recommended medications in our hospital is significantly lower than the national and international averages. In recent years, this situation has improved, especially since 2018 when pharmacists began participating in clinical decision-making, assisting doctors in rational drug use. As a result, the utilization rate of GDMT drugs has increased significantly compared to previous years. Additionally, we evaluated the impact of all medications on the prognosis of patients with HF. Despite some limitations in our study, most guideline-recommended medications demonstrated good therapeutic effects during the treatment process. Moreover, novel drugs for HF treatment, such as SGLT-2i and ivabradine, despite their low usage rates, still exhibited favorable efficacy. This provides additional evidence for rational drug use in clinical practice, contributing to improved patient outcomes.