Despite developments and improvements in treatment strategies, heart failure (HF) remains a
significant socioeconomic burden and leads to individual health problems due to its high
mortality and readmission rates. The latest 2016 European Society of Cardiology (ESC)
guideline recommends pharmacological treatment indicated in patients with symptomatic HF with
reduced ejection fraction. As the Class I level, the ESC guideline recommends 'ACEI, ARB,
ARNI, BB, MRA, Diuretics'. Guideline-directed medication therapy (GDMT) significantly
improved the survival of HF, particularly heart failure with reduced ejection fraction
(HFrEF). However, various registry studies demonstrated that HFrEF patients are frequently
undertreated. The gap exists between the ideal guideline and the current practice of HF
treatment. According to the observational nationwide study using the Korean National Health
Insurance Claims database, still, 28.6% of elderly heart failure patients did not receive
evidence-based treatment. To reduce the various burdens of HF at the patient and society
level, the right understanding of the disease and a nationwide systematic approach are
needed.
Recently, more data have emerged to support an expanded role for ARNIs in patients with
HFrEF. These data include their use as a de novo therapy in some patients naive to ACEIs or
ARB therapies, evidence for rapid improvement in patient-reported outcome measures, and the
demonstration of a reverse-remodeling effect of ARNIs in chronic HFrEF, independent of
background therapy with ACEIs/ARBs. However, the use of ARNI is still under expectation.
Clinical trials showed a fabulous result with the use of ARNI in HFrEF patients, however,
real-world data is still lacking. In Korea, the use of ARNI is increasing, however, the exact
use of ARNI is unknown, and only limited data reported the prescription pattern and outcomes
of ARNI in HFrEF patients.
Korea has an obligatory public health insurance system, the term of the Korean National
Health Insurance Service (NHIS) with which more than 97% of people are affiliated. All claim
data is electronically recorded and can be investigated for research purposes with the
approval of the Research Ethics Committee. The use of medications, dosage, cost, and the
effect on HF outcomes are assessable using the Korean NHIS database. Previous studies about
HF using the NHIS database have several limitations. They were conducted in small research
groups, and the operational definition of each study was different, and no studies were
conducted after sufficient discussions with HF expert opinions from the Korean Society of
Heart Failure.
This study aimed to evaluate the effectiveness, safety, and cost-effectiveness of ARNI and
ACEi/ARBs in real-world practice. This study could find out what the unmet medical needs are
in real-world practice. Furthermore, this study will be helpful to establish the healthcare
policy reimbursement policy or clinical practice guidelines for HF regarding HF medications
to reduce the burden of HF in Korea.
This is a non-interventional retrospective cohort study. This study will collect primary data
and secondary use data. The data will originate from the NHIS database. Clinical
characteristics (age, sex, BMI, WC, lipid profile, LFT, physical activity) will be
investigated. The treatment patterns are to be summarized using the proportion of patients
with good guideline adherence. Finally, it will compare the clinical outcomes
(hospitalization rate, cardiovascular and all-cause mortality) and medical costs of patients
groups who were treated with ARNI and without ARNI.
This study will collect primary data and secondary use data in patients with HF between 2017
and 2021. Data sources might include socioeconomic status, abstracts of primary clinical
records, electronic medical records, prescription drug files, laboratory reports, and
questionnaires for health behaviors. Concomitant or prior medications entered into the
database will be coded using the NHIS Reference List. Medical history/current medical
conditions will be coded using ICD-10 codes.
The Kaplan-Meier will be used for the survival curve to analyze the primary endpoints
(all-cause mortality, CV mortality, or first/recurrent any hospitalization ) and the related
results. Normally distributed continuous data are reported as mean ± standard deviation,
while non-parametric data are reported as median with interquartile range in brackets.
Categorical data are reported as numbers with percentages in brackets. Comparisons between
continuous variables were made using independent t-tests, while chi-square tests were made
for comparisons between categorical variables, with posthoc correction for tests including
more than two groups. Propensity score matching (maximum 1:5) will be performed for those who
had used ARNI and those who had not (ACEi/ARBs). The propensity score analysis balances
covariates between study groups of observational data using a propensity score, which is the
conditional probability of assignment to a particular group given observed covariates only.
The investigators will derive the propensity score model from a multiple logistic regression
that included age, sex, and underlying comorbidities. A stratified Cox proportional hazards
regression model for matched data will be used to evaluate the relation between the
treatments and study outcomes (mortality and/or first/recurrent any hospitalization).