Abstract
Objective
Dyslipidemia is a major modifiable risk factor for cardiovascular disease (CVD). We investigated temporal trends in CVD incidence and lipid-lowering therapy in individuals with dyslipidemia.
Methods
We conducted a nationwide population-based retrospective cohort study using the Korean National Health Insurance Service-National Sample Cohort (2010–2019) to assess age- and sex-standardized incidence rates of overall CVD, including ischemic heart disease, ischemic stroke, and heart failure, among adults aged ≥20 years. Dyslipidemia was identified based on the International Classification of Diseases, 10th Revision code E78 and/or the use of lipid-lowering agents. Prescription patterns for statins categorized by intensity, fibrates, and ezetimibe were analyzed.
Results
The overall age-standardized incidence of CVD among individuals with dyslipidemia declined markedly from 36.9 to 20.9 per 1,000 person-years. This downward trend was largely driven by substantial reductions in ischemic heart disease (from 29.2 to 15.0; a 48.6% decrease) and ischemic stroke (from 12.5 to 6.6; a 47.2% decrease). Meanwhile, the incidence of heart failure increased slightly, rising from 6.4 to 8.5 per 1,000 person-years. Statin use reached 95.3% by 2019 among dyslipidemic patients, but high-intensity statin use remained limited (4.7% of statin users). Ezetimibe use increased approximately four-fold, while fibrate use remained relatively unchanged.
Conclusion
CVD incidence declined substantially in the dyslipidemic population over the past decade. During the study period, lipid-lowering treatment patterns were characterized by widespread statin use and a substantial increase in ezetimibe prescriptions, although the use of high-intensity statins remained persistently low. These findings highlight opportunities to further optimize lipid-lowering strategies in high-risk populations.
Keywords: Dyslipidemias, Cardiovascular diseases, Incidence, Hypolipidemic agents, Korea
INTRODUCTION
Globally, cardiovascular disorders remain the leading cause of disease burden and mortality,1,2,3,4 with dyslipidemia serving as one of the most significant modifiable risk factors for atherosclerotic cardiovascular disease (ASCVD) events.5,6 The management of dyslipidemia has evolved substantially over the past two decades, driven by landmark clinical trials demonstrating the cardiovascular benefits of statin therapy and the introduction of novel lipid-lowering drugs such as ezetimibe and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors.7,8 However, beyond low-density lipoprotein cholesterol, atherogenic dyslipidemia characterized by elevated triglycerides, low high-density lipoprotein cholesterol, and lipoprotein(a) has been increasingly recognized as a major contributor to residual cardiovascular risk, particularly among individuals with insulin resistance, obesity, or diabetes, even in the era of widespread statin use.5,9 In addition, recent projections suggest that the burden of cardiovascular disease (CVD), including heart failure and stroke, will continue to rise in coming decades, driven by population aging, metabolic comorbidities, and widening health disparities.10 Given the substantial rise in dyslipidemia prevalence, the availability of potent therapeutic options, and the persistent limitations in their implementation, understanding trends in CVD incidence and lipid-lowering medication use within the dyslipidemic population is essential for guiding public health policy, clinical practice guidelines, and resource allocation for effective CVD prevention and management.
South Korea has experienced rapid demographic and epidemiologic transitions, including population aging, urbanization, and changing lifestyle patterns that have collectively influenced CVD epidemiology.11,12 ASCVD also remains a major public health concern, with an age-adjusted prevalence of 78.07 and a cumulative incidence of 60.32 per 1,000 individuals reported in 2015.13 Among major risk factors, dyslipidemia is highly prevalent and plays a central role in the development of ASCVD in the Korean population.6
Several previous reports have demonstrated that, despite the substantial health burden and widespread prevalence of CVD, the incidence of ASCVD has steadily declined during the last two decades, highlighting progress in preventive and therapeutic approaches.1,14,15 Similarly, a recent nationwide study in Korea focusing on patients with type 2 diabetes demonstrated declining temporal trends in ischemic heart disease and ischemic stroke, but also highlighted an increase in heart failure and suboptimal control of key cardiometabolic risk factors.16 Amidst this substantial prevalence, especially in high-risk groups, it is crucial to understand the evolving trends in incidence and to identify the factors contributing to change, as well as existing therapeutic gaps and limitations. However, no nationwide longitudinal analysis has specifically focused on CVD incidence and lipid-lowering medication use among individuals with dyslipidemia in Korea. Hence, this study aimed to provide a comprehensive analysis of CVD trends and lipid-lowering drug prescription patterns among Korean adults with dyslipidemia, using a decade-long nationwide cohort.
MATERIALS AND METHODS
1. Data source and study participants
This study is a nationwide retrospective cohort analysis using the Korean National Health Insurance Service National Sample Cohort (NHIS-NSC) from 2010 to 2019. The NHIS-NSC represents a nationally representative sample comprising approximately 1 million individuals (2% of the Korean population), selected through stratified random sampling based on age, sex, income level, and geographic region.17 The cohort design ensures representativeness of the entire Korean population and provides comprehensive longitudinal healthcare utilization data.18
We included all adults aged 20 years and older who maintained health insurance eligibility during the study period. Individuals with incomplete demographic data or those with less than one year of follow-up were excluded from the analysis. For incident CVD analyses, we applied disease-specific washout periods to ensure capture of new-onset events. Participants were followed from January 1, 2010 (or date of cohort entry) until the first occurrence of the outcome of interest, death, loss of eligibility from the NHIS, or December 31, 2019, whichever came first. We included all eligible adults in the NHIS-NSC dataset and did not perform an a priori sample size calculation, as the cohort size was determined by the sampling frame of the national database.
This study was conducted in accordance with the principles outlined in the Declaration of Helsinki (2024), and all procedures adhered to relevant guidelines and regulations. Because NHIS-NSC data are fully anonymized, the study was approved by the Institutional Review Board (IRB) of The Catholic University of Korea, Eunpyeong St. Mary’s Hospital, which waived the requirement for informed consent (IRB No. PIRB-20240711-001). The manuscript was prepared in compliance with the Strengthening the Reporting of Observational Studies in Epidemiology guidelines to ensure completeness and transparency.
2. Measurements and definitions
Dyslipidemia was defined using a composite criterion requiring either diagnosis with the International Classification of Diseases, 10th Revision (ICD-10) code E78 (disorders of lipoprotein metabolism and other lipidemias) during the study period, or prescription of any lipid-lowering medication including statins, fibrates, ezetimibe, or other lipid-lowering agents.19 We also collected information on age, sex, and comorbidities (hypertension, diabetes mellitus, etc.) based on ICD-10 codes. CVDs were defined using validated algorithms combining diagnostic codes with relevant healthcare utilization patterns. Ischemic heart disease was identified using ICD-10 codes I20–I25 with associated hospitalization.19 Ischemic stroke was defined using ICD-10 codes I63–I64 with hospitalization and brain imaging (computed tomography scan or magnetic resonance imaging scan).20 Heart failure was identified using ICD-10 code I50 with hospitalization.16,20
Lipid-lowering medications were classified according to established clinical categories.21 High-intensity statins included atorvastatin 40–80 mg daily and rosuvastatin 20–40 mg daily. Moderate-intensity statins included atorvastatin 10–20 mg daily, rosuvastatin 5–10 mg daily, simvastatin 20–40 mg daily, pravastatin 40–80 mg daily, lovastatin 40 mg daily, fluvastatin XL 80 mg daily, and pitavastatin 2–4 mg daily. Low-intensity statins comprised all other statin formulations and dosages. Fibrates included fenofibrate, bezafibrate, and related compounds. Ezetimibe included both monotherapy and fixed-dose combinations with statins.
To reduce misclassification of cardiovascular outcomes, we restricted outcome definitions to hospitalizations with primary ICD-10 diagnosis codes and, for stroke, required confirmatory brain imaging. To minimize immortal time bias, follow-up accrued from cohort entry until the earliest occurrence of the outcome, death, or end of the study. Because the NHIS-NSC is based on routinely collected administrative data, selection bias is expected to be minimal, although residual misclassification cannot be excluded.
3. Statistical analysis
Age- and sex-standardized incidence rates were calculated using the 2010 Korean standard population as the reference. Incidence rates were expressed per 1,000 person-years. Annual prescription rates were calculated as the proportion of patients with dyslipidemia receiving each medication class. Temporal trends were evaluated descriptively by comparing annual standardized incidence rates over the study period. Statistical significance was set at p<0.05 for all analyses. Given the descriptive nature of the study, we did not fit multivariable regression models to estimate adjusted effect sizes. Instead, we focused on age- and sex-standardized incidence rates and temporal trends. Key variables such as age, sex, and diagnosis codes were complete in the NHIS-NSC dataset; therefore, we did not perform imputation for missing data. All data processing was performed using SAS version 9.4 (SAS Institute Inc.).
RESULTS
1. Incidence of CVD in individuals with dyslipidemia
The study cohort included approximately 850,000 adults aged 20 years and older, contributing over 7.5 million person-years of follow-up (Table 1). The number of individuals identified with dyslipidemia increased substantially over the study period, from 69,088 in 2010 to 166,081 in 2019. Accordingly, the prevalence of dyslipidemia within the study cohort showed an increasing trend over time. The age-standardized incidence of overall CVD among individuals with dyslipidemia demonstrated a consistent downward trend over the study period, decreasing from 36.9 per 1,000 person-years in 2010 to 20.9 in 2019, corresponding to a 43.4% relative reduction (Table 2 and Fig. 1). The age-standardized incidence rate for ischemic heart disease decreased markedly from 29.2 per 1,000 person-years in 2010 to 15.0 in 2019, representing a 48.6% relative reduction. The sharpest decline occurred between 2010 and 2015, followed by a more gradual decrease thereafter. Similar patterns emerged for ischemic stroke, with incidence rates declining from 12.5 to 6.6 per 1,000 person-years over the same period, reflecting a 47.2% relative reduction. The decline in ischemic stroke showed a more linear pattern compared with ischemic heart disease. Heart failure presented a contrasting trend (Table 2 and Fig. 1). The age-standardized incidence rate increased from 6.4 to 8.5 per 1,000 person-years during the study period, representing a 32.8% relative increase.
Table 1. Temporal trends in baseline characteristics of the study population from 2010 to 2019.
| Characteristics | 2010 | 2011 | 2012 | 2013 | 2014 | 2015 | 2016 | 2017 | 2018 | 2019 | |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Patients with dyslipidemia | 69,088 | 76,903 | 86,182 | 95,157 | 106,010 | 116,556 | 131,566 | 143,738 | 153,370 | 166,081 | |
| Prevalence of dyslipidemia | 8.6 | 9.5 | 10.5 | 11.5 | 12.7 | 13.8 | 15.4 | 16.7 | 17.6 | 19.0 | |
| Age (yr) | 60.3±11.8 | 60.6±11.8 | 61.0±11.9 | 61.5±11.9 | 61.9±11.9 | 62.2±12.0 | 62.4±12.0 | 62.6±12.0 | 63.0±12.1 | 63.3±12.2 | |
| Sex | |||||||||||
| Male | 30,336 (43.9) | 34,066 (44.3) | 38,364 (44.5) | 42,582 (44.7) | 48,049 (45.3) | 53,168 (45.6) | 60,734 (46.2) | 66,903 (46.5) | 72,294 (47.1) | 78,939 (47.5) | |
| Female | 38,752 (56.1) | 42,837 (55.7) | 47,818 (55.5) | 52,575 (55.3) | 57,961 (54.7) | 63,388 (54.4) | 70,832 (53.8) | 76,835 (53.5) | 81,076 (52.9) | 87,142 (52.5) | |
| Diabetes | 20,841 (30.2) | 23,715 (30.8) | 26,537 (30.8) | 29,599 (31.1) | 34,219 (32.3) | 38,124 (32.7) | 43,003 (32.7) | 47,741 (33.2) | 52,255 (34.1) | 57,266 (34.5) | |
| Hypertension | 45,598 (66.0) | 49,892 (64.9) | 56,798 (65.9) | 62,689 (65.9) | 69,364 (65.4) | 75,090 (64.4) | 82,549 (62.7) | 89,268 (62.1) | 96,183 (62.7) | 103,972 (62.6) | |
Variables are presented as mean ± standard deviation or number (%).
Data source: National Health Insurance Service–National Sample Cohort. Study population included adults aged ≥20 years.
Dyslipidemia was defined as the presence of International Classification of Diseases, 10th Revision code E78 or the use of lipid-lowering medications (statins, ezetimibe, or fibrates).
Table 2. Age-standardized incidence of CVDs per 1,000 person-years from 2010 to 2019.
| Group | Disease | 2010 | 2011 | 2012 | 2013 | 2014 | 2015 | 2016 | 2017 | 2018 | 2019 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall | |||||||||||
| Ischemic heart disease | 29.2 | 26.7 | 25.7 | 22.6 | 22.0 | 20.8 | 16.8 | 16.7 | 16.0 | 15.0 | |
| Ischemic stroke | 12.5 | 11.1 | 11.3 | 9.4 | 8.7 | 8.5 | 7.6 | 7.5 | 6.8 | 6.6 | |
| Heart failure | 6.4 | 7.6 | 7.1 | 7.1 | 7.1 | 7.7 | 7.7 | 8.8 | 9.0 | 8.5 | |
| Any CVD | 36.9 | 33.0 | 32.8 | 28.6 | 27.7 | 26.4 | 23.0 | 23.0 | 22.3 | 20.9 | |
| Men | |||||||||||
| Ischemic heart disease | 35.6 | 32.5 | 31.3 | 27.7 | 27.2 | 25.2 | 19.9 | 20.6 | 18.7 | 18.1 | |
| Ischemic stroke | 14.1 | 12.6 | 12.5 | 11.2 | 10.3 | 9.7 | 9.5 | 8.4 | 7.9 | 7.6 | |
| Heart failure | 6.5 | 7.3 | 8.1 | 7.6 | 7.6 | 8.4 | 8.0 | 9.2 | 10.0 | 9.0 | |
| Any CVD | 44.0 | 39.8 | 39.4 | 34.8 | 33.7 | 31.0 | 27.3 | 27.1 | 25.9 | 24.7 | |
| Women | |||||||||||
| Ischemic heart disease | 24.2 | 21.9 | 21.0 | 18.2 | 17.3 | 16.7 | 13.6 | 12.8 | 13.1 | 11.6 | |
| Ischemic stroke | 11.2 | 9.9 | 10.1 | 7.7 | 7.2 | 7.2 | 5.7 | 6.5 | 5.6 | 5.4 | |
| Heart failure | 6.3 | 7.8 | 6.3 | 6.6 | 6.5 | 6.9 | 7.3 | 8.2 | 7.7 | 7.8 | |
| Any CVD | 31.4 | 27.5 | 27.2 | 23.2 | 22.2 | 22.1 | 18.7 | 18.8 | 18.4 | 16.8 |
Values are presented as age-standardized incidence rates per 1,000 person-years.
CVD, cardiovascular disease.
Fig. 1. Annual age-standardized incidence rates for ischemic heart disease, ischemic stroke, and heart failure among adults with dyslipidemia (per 1,000 person-years).
Sex-based differences were generally modest for CVD incidence trends, though men consistently demonstrated higher absolute rates for ischemic heart disease, ischemic stroke, and heart failure (Fig. 2).
Fig. 2. Changes in the incidence of CVDs in patients with dyslipidemia according to sex. (A) Ischemic heart disease, (B) Ischemic stroke, (C) Heart failure, (D) Any CVD.
CVD, cardiovascular disease.
2. Medications for dyslipidemia
Analysis of lipid-lowering medication prescriptions revealed distinct patterns across drug classes (Table 3 and Fig. 3). Overall statin prescriptions among dyslipidemia patients remained consistently elevated, reaching 95.3% by 2019. However, examination of the statin intensity distribution revealed important gaps in evidence-based prescribing. High-intensity statin utilization remained remarkably low throughout the study period, increasing only marginally from 3.6% in 2014 to 4.7% in 2019. Moderate-intensity formulations comprised approximately 85-90% of all statin prescriptions, while low-intensity statins accounted for the remainder.
Table 3. Lipid-lowering prescription rates among dyslipidemia patients from 2014 to 2019.
| Population | Medication | 2014 | 2015 | 2016 | 2017 | 2018 | 2019 | |
|---|---|---|---|---|---|---|---|---|
| Total dyslipidemic population | ||||||||
| Ezetimibe | 5.5 | 5.6 | 11.6 | 15.5 | 17.6 | 20.3 | ||
| Fibrate | 10.8 | 10.3 | 9.8 | 10.2 | 10.4 | 10.4 | ||
| Statin (overall) | 94.6 | 95.1 | 95.4 | 95.2 | 95.2 | 95.3 | ||
| Low intensity | 4.6 | 4.4 | 3.4 | 3.0 | 3.1 | 2.9 | ||
| Moderate intensity | 91.8 | 91.2 | 92.1 | 92.5 | 92.2 | 92.4 | ||
| High intensity | 3.6 | 4.4 | 4.5 | 4.5 | 4.7 | 4.7 | ||
| Dyslipidemia with ischemic heart disease | ||||||||
| Ezetimibe | 6.7 | 7.3 | 10.8 | 18.2 | 21.0 | 25.7 | ||
| Fibrate | 5.8 | 5.5 | 5.3 | 5.5 | 5.7 | 6.4 | ||
| Statin (overall) | 98.8 | 98.6 | 98.8 | 98.9 | 99.0 | 99.0 | ||
| Low intensity | 4.0 | 4.1 | 2.9 | 2.7 | 2.5 | 2.9 | ||
| Moderate intensity | 84.5 | 81.5 | 81.9 | 81.7 | 80.3 | 79.7 | ||
| High intensity | 11.5 | 14.4 | 15.2 | 15.6 | 17.2 | 17.4 | ||
| Dyslipidemia with ischemic stroke | ||||||||
| Ezetimibe | 7.5 | 6.1 | 9.2 | 13.0 | 14.4 | 18.4 | ||
| Fibrate | 6.1 | 6.1 | 6.0 | 5.4 | 4.9 | 5.3 | ||
| Statin (overall) | 99.1 | 99.0 | 99.2 | 98.9 | 99.2 | 99.4 | ||
| Low intensity | 4.2 | 4.2 | 2.5 | 2.3 | 1.6 | 2.5 | ||
| Moderate intensity | 79.3 | 77.0 | 76.3 | 77.4 | 75.2 | 74.6 | ||
| High intensity | 16.5 | 18.8 | 21.2 | 20.3 | 23.2 | 22.9 | ||
| Dyslipidemia with heart failure | ||||||||
| Ezetimibe | 5.5 | 6.5 | 8.5 | 14.2 | 16.5 | 20.1 | ||
| Fibrate | 5.9 | 4.9 | 5.7 | 5.4 | 6.1 | 6.1 | ||
| Statin (overall) | 98.2 | 98.8 | 98.6 | 98.5 | 98.3 | 98.6 | ||
| Low intensity | 3.9 | 3.9 | 3.1 | 3.0 | 3.3 | 3.5 | ||
| Moderate intensity | 87.5 | 84.4 | 84.9 | 85.2 | 83.9 | 84.5 | ||
| High intensity | 8.6 | 11.7 | 12.0 | 11.8 | 12.8 | 12.0 | ||
| Dyslipidemia with any CVD | ||||||||
| Ezetimibe | 6.6 | 6.9 | 10.4 | 16.8 | 19.2 | 23.3 | ||
| Fibrate | 5.9 | 5.8 | 5.6 | 5.5 | 5.8 | 6.3 | ||
| Statin (overall) | 98.7 | 98.7 | 98.7 | 98.8 | 98.8 | 98.9 | ||
| Low intensity | 4.1 | 3.9 | 2.8 | 2.6 | 2.6 | 2.9 | ||
| Moderate intensity | 84.1 | 81.6 | 81.6 | 82.1 | 80.7 | 80.2 | ||
| High intensity | 11.8 | 14.5 | 15.6 | 15.3 | 16.7 | 16.9 | ||
Values are expressed as prescription rates (%).
CVD, cardiovascular disease.
Fig. 3. Lipid-lowering prescription rates among dyslipidemia patients (2014–2019).
According to the 2019 data, among patients with dyslipidemia and comorbid CVD, statin prescriptions were distributed as follows: high-intensity statins in 16.9%, moderate-intensity in 80.2%, and low-intensity in 2.9% (Fig. 4A). In patients with dyslipidemia and ischemic heart disease, high-, moderate-, and low-intensity statins were prescribed in 17.4%, 79.7%, and 2.9%, respectively (Fig. 4B). For those with ischemic stroke, the corresponding proportions were 22.9% (high), 74.6% (moderate), and 2.5% (low) (Fig. 4C). Among patients with heart failure, 12.0% received high-intensity statins, 84.5% moderate-intensity, and 3.5% low-intensity (Fig. 4D).
Fig. 4. Statin intensity by comorbid cardiovascular condition in dyslipidemia patients in 2019. Values represent the proportion of patients receiving statins (%). (A) Any CVD, (B) Ischemic heart disease, (C) Ischemic stroke, (D) Heart failure.
CVD, cardiovascular disease.
A notable change in prescription patterns was observed with ezetimibe use (Table 3 and Fig. 3). Prescription rates increased dramatically from 5.5% in 2014 to 20.3% in 2019, representing nearly a four-fold increase. This uptake accelerated particularly after 2016, temporally coinciding with the dissemination of the Improved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT) results,22 and subsequent guideline updates advocating combination therapy for high-risk patients. In contrast, fibrate prescription rates demonstrated remarkable stability, fluctuating between 9.8% and 10.8% throughout the observation period (Table 3 and Fig. 3).
DISCUSSION
This comprehensive decade-long analysis provides unprecedented insights into the evolving landscape of CVD epidemiology and lipid management practices among Korean individuals with dyslipidemia. In this nationwide cohort study spanning 2010 to 2019, the prevalence of dyslipidemia among Koreans increased substantially over time, while the incidence of ischemic heart disease and ischemic stroke decreased considerably within the dyslipidemic population. In contrast, the incidence of heart failure demonstrated a gradual upward trend over the same period. Although statin therapy was widely adopted, the use of high-intensity statins remained limited, even among patients with established ASCVD. Ezetimibe use increased consistently over time, whereas fibrate prescriptions remained stable throughout the study period. Given the descriptive and observational nature of this nationwide claims-based analysis, these temporal associations should be interpreted cautiously as ecological observations at the population level.
Despite the increasing proportion of individuals with dyslipidemia over the study period, the marked reductions in the incidence of ischemic heart disease and ischemic stroke among this population represent an encouraging improvement in cardiovascular outcomes. These declines align with favorable trends reported in developed countries,14,15 but demonstrate that similar progress has been achieved in Korea despite unique demographic, genetic, and healthcare system characteristics. These trends likely occurred in the context of multiple concurrent changes in cardiovascular prevention and risk factor management. Widespread implementation of evidence-based cardiovascular prevention strategies, including systematic blood pressure management, diabetes care optimization, and increased lipid-lowering therapy adoption, has created synergistic risk reduction effects.21,23,24 Simultaneously, comprehensive public health initiatives addressing smoking cessation, dietary improvement, and physical activity promotion have modified population-level risk factor profiles.25,26,27
Nevertheless, interpretation of these temporal trends should also consider potential changes in the composition of the dyslipidemic population over time. The dyslipidemic population represents a heterogeneous group with widely varying baseline cardiovascular risk profiles. Over time, changes in screening practices, treatment eligibility, and clinical recognition may have increased the number of individuals identified with dyslipidemia, potentially altering the composition of the study population. Such shifts in case mix, including the relative proportions of primary versus secondary prevention populations, may influence both cardiovascular incidence trends and prescribing patterns. Therefore, the observed temporal trends should be interpreted with caution, as part of the decline in cardiovascular incidence may reflect changes in the underlying risk composition of the dyslipidemic population in addition to improvements in cardiovascular risk management. This consideration is particularly relevant given that dyslipidemia in the present study was defined based on healthcare utilization, reflecting physician diagnostic awareness and treatment patterns.
The observed trends in heart failure incidence among the dyslipidemic population warrant careful interpretation. Heart failure incidence varies widely depending on case ascertainment methods, clinical recognition, and the underlying cardiovascular risk profile of the population. Although age-standardized incidence rates were used to account for differences in population age structure, such standardization primarily adjusts for the distribution of age groups and may not fully capture qualitative changes associated with an aging population. In particular, improved survival after acute cardiovascular events has expanded the population at risk for heart failure. In addition, evolving clinical recognition and diagnostic practices, such as the increasing use of natriuretic peptide-based diagnostic frameworks introduced in the 2016 European Society of Cardiology guidelines,28 may have contributed to greater detection of heart failure in clinical practice. Consistent with this interpretation, nationwide population-based data indicate that although age-standardized heart failure incidence may stabilize or vary modestly over time, overall prevalence continues to increase due to improved survival and the growing population living with CVD.29
The prescription pattern analysis reveals both successes and opportunities in contemporary lipid management. The achievement of over 95% statin utilization among dyslipidemia patients represents successful translation of evidence-based guidelines into clinical practice and compares favorably with international benchmarks.30 However, the persistently low adoption of high-intensity statin therapy among high-risk patients represents a substantial gap between evidence-based recommendations and clinical practice.21 Notably, even among patients with established ASCVD, fewer than one in four received high-intensity statin therapy. This pattern suggests multiple potential barriers, including physician concerns about statin-associated adverse effects, patient tolerance considerations, insurance coverage limitations, and incomplete awareness of updated recommendations emphasizing intensive lipid-lowering for secondary prevention and high-risk primary prevention scenarios.31,32 The low high-intensity statin utilization suggests that national guideline efforts should promote not only statin initiation but also appropriate intensity titration, particularly in high-risk populations such as those with diabetes, prior ASCVD, or multiple risk factors.21,33 Additionally, addressing patient concerns about intensive lipid-lowering therapy through enhanced shared decision-making approaches and appropriate safety monitoring may improve acceptance of evidence-based regimens.
Meanwhile, this finding should be interpreted in the context of evolving lipid-lowering treatment strategies. Ezetimibe use increased approximately four-fold during the study period, reaching 20.3% by 2019. Ezetimibe became commercially available in Korea in 2005. Importantly, reimbursement criteria for statin–ezetimibe combination therapy were broadened in May 2015, reducing barriers to clinical use. The marked increase in ezetimibe prescriptions likely reflects the combined influence of reimbursement policy changes, dissemination of the IMPROVE-IT trial results,22 and subsequent guideline updates advocating more intensive lipid-lowering strategies. Furthermore, recent clinical evidence from Korea supports this trend, showing that moderate-intensity statin combined with ezetimibe achieves comparable cardiovascular risk reduction to high-intensity statin monotherapy while offering superior safety and tolerability profiles.34 In addition, reflecting very recent expert consensus advocating upfront ezetimibe in combination with statins for high-risk patients, ezetimibe use is expected to further increase in clinical practice.35 Taken together, these findings indicate that contemporary lipid-lowering strategies may increasingly rely on combination therapy rather than high-intensity statin monotherapy alone.
The stability of fibrate prescriptions at approximately 10% suggests these agents maintain a consistent niche role in specific clinical scenarios, particularly for patients with severe hypertriglyceridemia or mixed dyslipidemia patterns inadequately addressed by statin monotherapy.36 This pattern aligns with current guideline recommendations positioning fibrates as adjunctive therapy for selected patients.21,33
Several limitations warrant acknowledgment. First, because this study was based on nationwide administrative claims data, caution is warranted in interpreting temporal associations between lipid-lowering medication use and CVD incidence. These observations should be regarded as hypothesis-generating rather than causal. In addition, administrative data may introduce misclassification bias,37 particularly for evolving conditions such as heart failure, where diagnostic criteria have changed during the study period. The dyslipidemia definition based on diagnostic codes and medication prescriptions may not capture all individuals with lipid abnormalities, particularly those with mild elevations not meeting treatment thresholds. Second, clinical parameters such as lipid levels, blood pressure control, and medication adherence are not captured in administrative databases, limiting our ability to assess treatment appropriateness and effectiveness. Third, temporal changes in clinical practice patterns, diagnostic technology availability, and healthcare accessibility may have influenced observed trends in ways that cannot be fully controlled through analytical approaches. Fourth, this study did not evaluate the use of omega-3 fatty acid agents. These agents are available over-the-counter in South Korea, are consumed at highly variable doses, and have not demonstrated consistent cardiovascular outcome benefits in clinical trials.38 We also did not assess the use of injectable PCSK9 inhibitors; although approved in South Korea in 2017, these agents were not reimbursed for their major indications until January 2020, and their use during the study period was negligible. In addition, we did not distinguish between ezetimibe monotherapy and its use in fixed-dose combinations or as concomitant therapy with statins. Fifth, analyses of lipid-lowering medication use were limited to 2014 onward, reflecting the introduction of high-intensity statin recommendations in the 2013 American College of Cardiology/American Heart Association guideline and the subsequent emergence of IMPROVE-IT trial evidence shaping contemporary clinical practice.32,39 Finally, because we did not adjust for all potential confounders such as socioeconomic status, lifestyle factors, or detailed clinical parameters, residual confounding cannot be excluded.
In this nationwide cohort study, CVD incidence declined substantially in the dyslipidemic population over the past decade. This observation should be interpreted in the context of potential changes in the underlying cardiovascular risk composition of the cohort. Lipid-lowering treatment patterns evolved during the same period, with widespread statin use, persistently low use of high-intensity statins, and a substantial increase in ezetimibe prescriptions. These findings highlight opportunities to further optimize lipid-lowering strategies in high-risk populations.
Footnotes
Funding: This study was supported by the Korean Society of Lipid and Atherosclerosis.
Conflict of Interest: The authors have no conflicts of interest to declare.
Data Availability Statement: The data analyzed in this study are not publicly available due to privacy and data protection regulations. Access to the data can be obtained from the National Health Insurance Service (NHIS) of Korea upon application and approval.
- Conceptualization: Kwon O, Ahn J.
- Data curation: Han K.
- Methodology: Han K, Ahn J.
- Supervision: Lee SY, Kim B.
- Visualization: Kwon O, Han K.
- Writing - original draft: Kwon O, Youn JC, Lee SY, Kim B, Ahn J.
- Writing - review & editing: Ahn J.
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