Abstract
Background
Therapeutic inertia is defined as the failure to provide guideline-directed therapy and is a barrier to achieving optimal clinical outcomes. We aimed to evaluate therapeutic inertia in statin therapy after percutaneous coronary intervention (PCI) and its association with patient characteristics and physician’s prescribing practice.
Methods
We analyzed the medical claims data on patients undergoing PCI using National Health Insurance Service in Republic of Korea. The primary outcome of interest was therapeutic inertia, defined as not providing high-intensity statin (HIS) therapy within 30 days after discharge for PCI. To identify statin use in identical clinical setting, we restricted study duration to between 2013 American College of Cardiology/American Heart Association cholesterol guideline and publications of RACING (Randomized Comparison of Efficacy and Safety of Lipid-lowering with Statin Monotherapy Versus Statin–ezetimibe Combination for High-risk Cardiovascular Disease) and LODESTAR (Low-Density Lipoprotein Cholesterol-Targeting Statin Therapy Versus Intensity-Based Statin Therapy in Patients With Coronary Artery Disease) trials that demonstrated non-inferiority of alternative statin strategies compared with HIS therapy in atherosclerotic cardiovascular disease. We also assessed patient characteristics affecting HIS prescription, statin switching before and after PCI among previous statin users, and impact of previous statin regimen on prescribing of HIS.
Results
Of 204,708 participants (mean age 66.5 ± 11.3 years, 30.8% female, 56.6% previous statin users, 43.4% previous statin nonusers), therapeutic inertia was identified in 64.1%, and HIS prescription rate was higher in previous statin nonusers (42.0%) than in previous statin users (31.1%). There were few differences in patient characteristics as positive (male and acute coronary syndrome as indication for PCI) and negative (increase of age, comorbidities, and cardiovascular medications) predictors of HIS prescription between previous statin users and nonusers. Because 79.1% of previous HIS users and 23.8% of previous non-HIS users received HIS following PCI, previous HIS users were more likely to be prescribed HIS as compared to previous statin nonusers (odds ratio, 5.42; 95% confidence intervals, 4.44–6.61) and previous non-HIS users (odds ratio, 12.30; 95% confidence intervals, 9.95–15.19).
Conclusions
Suboptimal HIS prescription following PCI was substantially affected by patient characteristics and the practice of repetitive prescribing of previous statin without guideline-directed titration.
Clinical trial number
Not applicable.
Supplementary Information
The online version contains supplementary material available at 10.1186/s12872-025-05081-0.
Keywords: Therapeutic inertia, Statin, Percutaneous coronary intervention, Cardiovascular disease, Coronary artery disease, Secondary prevention
Introduction
Patients who have undergone percutaneous coronary intervention (PCI) are indicated to receive statin therapy to reduce the mortality and adverse cardiovascular events [1–3]. High-intensity statin (HIS) therapy has been recommended as a first-line strategy of lipid-lowering treatment for secondary prevention in patients with atherosclerotic cardiovascular disease (ASCVD) based on its superior efficacy in reducing cardiovascular events compared with a low- to moderate-intensity statin therapy [4–7]. However, suboptimal utilization of HIS and residual cardiovascular risk among patients with ASCVD in the clinical settings remain an important issue worldwide [8–13]. In the previous studies that investigated the gaps between clinical guidelines and clinical practices in statin therapy, various patient- or system-level factors, such as statin intolerance, poor adherence, or social media focusing statin-associated side effects, have been described as the barriers for HIS utilization in patients with ASCVD [14–18]. Some patient characteristics, such as old age, female sex, or comorbidities, have also influenced the prescribing of HIS, thereby playing a role as physician-level barriers [8, 10, 11]. Furthermore, a HIS was more likely to be prescribed by cardiologist and more likely to be prescribed to previous HIS users, suggesting that a statin therapy may be affected by inertia in medical treatment, physician’s prescribing practice, or concerns regarding dose-dependent statin-associated side effects [8, 10, 11, 19–21]. These findings indicate that the reasons for suboptimal use of HIS in patients with ASCVD are multiple and complex.
Therapeutic inertia in the management of chronic medical disease was defined as a failure to initiate or intensify treatment although therapeutic goals are not achieved and has been recognized as a representative physician-level barrier [19, 22–24]. Assessing trends in statin therapy after PCI and factors associated with prescribing of HIS may help understand the specific reasons for failure to provide guideline-directed statin therapy. Using large-scale medical claims data, we evaluated therapeutic inertia in statin therapy for secondary prevention among patients undergoing PCI. In particular, we aimed to demonstrate the association of HIS prescription with patient characteristics as well as physician’s prescribing practice.
Methods
Data source and collection
This retrospective population-based cohort study analyzed the data in the National Health Insurance Service (NHIS), a sole and compulsory healthcare system in Republic of Korea that covers an entire nationwide population. The detailed structure and use of the NHIS system have been described previously [25]. In this database, diagnoses are coded using the Korean Standard Classification of Diseases based on the International Classification of Diseases system; Procedures and medication prescriptions are coded with the Electronic Data Interchange system of the Health Insurance Review and Assessment in Republic of Korea and World Health Organization Anatomical Therapeutic Chemical code, respectively. To identify trends of statin use in an identical clinical setting, we restricted a study duration as the period after the publication of the 2013 American College of Cardiology/American Heart Association cholesterol guideline and before the publications of the two randomized controlled trials, RACING (Randomized Comparison of Efficacy and Safety of Lipid-lowering with Statin Monotherapy Versus Statin–ezetimibe Combination for High-risk Cardiovascular Disease) trial and LODESTAR (Low-Density Lipoprotein Cholesterol-Targeting Statin Therapy Versus Intensity-Based Statin Therapy in Patients With Coronary Artery Disease) trial, that demonstrated a non-inferiority of alternative statin strategies compared with a HIS therapy in ASCVD [26, 27]. Thus, we used the data of patients who were aged 18 years or older and underwent PCI between January 1, 2014 and December 31, 2017. The detailed definitions and codes used in this study are presented in Additional File 1: Table S1.
Statin exposure
We identified a prescription of statin from 365 days prior to PCI through 30 days following discharge for PCI among study participants. Patients with any statin use in the 365 days prior to PCI were classified as previous statin users, and intensity of previous statin was determined by preceding statin most proximate to PCI. Statin included atorvastatin, rosuvastatin, simvastatin, fluvastatin, lovastatin, pitavastatin, and pravastatin. HIS included atorvastatin 40 mg or 80 mg and rosuvastatin 20 mg. Given difference between the guidelines [1–4], low-density lipoprotein cholesterol level was not used as a measure of interest, whereas HIS use after PCI, which has been established across the guidelines, was defined as a standard management. As there was no clear role of statin and ezetimibe combination for secondary prevention at that time, we identified the use of ezetimibe in addition to statin but did not reflect this in the determination of guideline concordance. Switching statin among previous statin users was assessed using the conversion from the final statin before PCI to the first statin after PCI. Up-titration was defined as a conversion from non-HIS therapy to HIS therapy and down-titration was defined as a conversion from HIS therapy to non-HIS therapy.
Outcomes
The primary outcome of interest was therapeutic inertia in statin therapy after PCI measured by the percentage of patients who did not receive HIS therapy within 30 days after hospital discharge for the index PCI. Additional outcomes of interest were the patient characteristics associated with HIS prescription, the trends in statin switching before and after PCI among previous statin users, and the impact of previous statin use and its intensity on prescribing of HIS after PCI.
Statistical analysis
The study period was divided into the first- and second-halves annually. The chi-square test was used to analyze categorical variables and the independent t-test was used to analyze continuous variables. Categorical variables were presented as absolute numbers and percentages, and continuous variables were presented as means and standard deviations. Demographics, comorbidities, indication for PCI, and concomitant cardiovascular medication use between HIS and non-HIS users were compared, and all the variables showing statistical significance with P value less than 0.05 in univariable analysis were entered into the multivariable logistic regression model to identify the predictors of HIS prescription and evaluate the association between HIS prescription after PCI and previous statin strategy. As only 5.5% of the study population received ezetimibe after PCI, with most patients identified after the second half of 2016, univariable and multivariable analyses for the predictors of HIS prescription were performed among patients who received a statin monotherapy after PCI. As overall participants were divided into either previous statin users or nonusers according to statin use before PCI, statin-requiring medical conditions, such as dyslipidemia, stroke, or myocardial infarction, were not entered into the univariable and multivariable analyses to avoid a duplication bias. Statistical analyses were conducted using R software, version 4.0.0 (R Foundation for Statistical Computing, Vienna, Austria) and P value less than 0.05 was considered statistically significant.
Results
Study population and statin use after percutaneous coronary intervention
The current study included 204,708 patients consisting of 115,793 previous statin users and 88,915 previous statin nonusers (Additional File 1: Table S2). The mean age was 66.5 ± 11.3 years and 30.8% were female. The proportion of patients who were prescribed a HIS, non-HIS, and no statin after index PCI was 35.9%, 61.5%, and 2.6%, respectively, presenting 64.1% of patients undergoing PCI were upon therapeutic inertia in statin therapy after PCI. Percentage of HIS use after PCI was higher in previous statin nonusers (42.0%) than in previous statin users (31.1%). Among previous statin users, the patients who were prescribed a HIS after PCI were younger (mean age, 65.8 ± 10.8 years vs. 67.9 ± 10.4 years; P < 0.001) and comprised with more male (69.6% vs. 66.0%; P < 0.001) than those who were prescribed a non-HIS (Table 1). Further, they were more likely to have myocardial infarction as indication for PCI and less likely to have stable and unstable angina as indication for PCI, various comorbidities, and concomitant cardiovascular medications. Fairly similar results were observed in previous statin nonusers. Ezetimibe use before PCI was identified in 3.1% of previous HIS users and 9.0% of previous non-HIS users.
Table 1.
Baseline characteristics of the study population
| Previous statin users, n (%) | Previous statin nonusers, n (%) | |||||
|---|---|---|---|---|---|---|
| HIS after PCI (n = 35457) | Non-HIS after PCI (n = 71332) | P value | HIS after PCI (n = 36922) | Non-HIS after PCI (n = 44407) | P value | |
| Age, mean, y | 65.8 ± 10.8 | 67.9 ± 10.4 | < 0.001 | 64.6 ± 12.4 | 66.9 ± 12.1 | < 0.001 |
| Age strata | < 0.001 | < 0.001 | ||||
| <50 | 2573 (7.3) | 3278 (4.6) | 4414 (12.0) | 3742 (8.4) | ||
| 50–59 | 7685 (21.7) | 12,408 (17.4) | 8945 (24.2) | 9097 (20.5) | ||
| 60–69 | 11,308 (31.9) | 22,239 (31.2) | 9913 (26.8) | 11,797 (26.6) | ||
| ≥70 | 13,891 (39.2) | 33,407 (46.8) | 13,650 (37.0) | 19,771 (44.5) | ||
| Male | 24,674 (69.6) | 47,061 (66.0) | < 0.001 | 28,000 (75.8) | 31,367 (70.6) | < 0.001 |
| Hypertension | 31,751 (89.5) | 66,139 (92.7) | < 0.001 | 24,445 (66.2) | 32,680 (73.6) | < 0.001 |
| Diabetes | 16,541 (74.9) | 56,110 (78.7) | < 0.001 | 19,273 (52.2) | 26,139 (58.9) | < 0.001 |
| Heart failure | 16,821 (47.4) | 37,784 (53.0) | < 0.001 | 9277 (25.1) | 14,070 (31.7) | < 0.001 |
| AF | 3280 (9.3) | 8411 (11.8) | < 0.001 | 2089 (5.7) | 3434 (7.7) | < 0.001 |
| CKD | 3708 (10.5) | 9239 (13.0) | < 0.001 | 2147 (5.8) | 3487 (7.9) | < 0.001 |
| Malignancy | 5613 (15.8) | 13,515 (18.9) | < 0.001 | 4807 (13.0) | 7163 (16.1) | < 0.001 |
| Indication for PCI | < 0.001 | < 0.001 | ||||
| MI | 10,529 (29.7) | 12,228 (17.1) | 21,442 (58.2) | 17,606 (39.6) | ||
| UA | 12,424 (35.0) | 27,243 (38.2) | 8827 (23.9) | 14,190 (32.0) | ||
| SA | 9837 (27.7) | 25,720 (36.1) | 5257 (14.2) | 10,040 (22.6) | ||
| Others | 2667 (7.5) | 6141 (8.6) | 1396 (3.8) | 2571 (5.8) | ||
| Aspirin | 14,398 (40.6) | 33,631 (47.1) | < 0.001 | 5488 (14.9) | 8858 (19.9) | < 0.001 |
| P2Y12 inhibitor | 6408 (18.1) | 16,348 (22.9) | < 0.001 | 1414 (3.8) | 2567 (5.8) | < 0.001 |
| ACE inhibitor | 1562 (4.4) | 3511 (4.9) | < 0.001 | 406 (1.1) | 682 (1.5) | < 0.001 |
| ARB | 14,238 (40.2) | 30,397 (42.6) | < 0.001 | 8337 (22.6) | 11,743 (26.4) | < 0.001 |
| BB | 8945 (25.2) | 21,574 (30.2) | < 0.001 | 3149 (8.5) | 5069 (11.4) | < 0.001 |
| CCB | 11,969 (33.8) | 26,462 (37.1) | < 0.001 | 7825 (21.2) | 10,819 (24.4) | < 0.001 |
Abbreviations: ACE Angiotensin-converting enzyme, AF Atrial fibrillation, ARB Angiotensin receptor blocker; BB Beta-blocker, CCB Calcium-channel blocker, CKD Chronic kidney disease, HIS High-intensity statin, MI Myocardial infarction, PCI Percutaneous coronary intervention, SA Stable angina, UA Unstable angina
From the first half of 2014 through the second half of 2017, prescribing of HIS with or without ezetimibe after PCI increased among both previous statin users (25.0–35.0%) and previous statin nonusers (33.4–48.2%), whereas non-HIS use decreased among both previous statin users (73.4–64.0%) and previous statin nonusers (61.0–47.9%) (Fig. 1, Additional File 1: Tables S3 and S4). Ezetimibe use was rare through first half of 2016 and slightly increased thereafter among both populations, with an overall prescription rate of 5.5%.
Fig. 1.
Trends in statin prescription after PCI. From the first half of 2014 through the second half of 2017, HIS prescription increased among both previous statin users (25.0–35.0%) (left) and previous statin nonusers (33.4–48.2%) (right) and non-HIS prescription decreased among both previous statin users (73.4–64.0%) and previous statin nonusers (61.0–47.9%). Ezetimibe use was rare through first half of 2016 and slightly increased thereafter. Abbreviations: HIS, high-intensity statin; PCI, percutaneous coronary intervention.
Predictors of high-intensity statin prescription
In previous statin users, male (OR, 1.009; 95% CI, 1.003–1.015; P = 0.002), myocardial infarction and unstable angina as indications for PCI (OR, 1.172; 95% CI, 1.159–1.185; P < 0.001 and OR, 1.012; 95% CI, 1.001–1.022; P = 0.028), and angiotensin receptor blocker use (OR, 1.010; 95% CI, 1.003–1.016; P = 0.002) were the independent predictors of HIS prescription after PCI in multivariable analysis (Table 2). Similarly, in previous statin nonusers, male (OR, 1.027; 95% CI, 1.018–1.035; P < 0.001) and myocardial infarction and unstable angina as indications for PCI (OR, 1.189; 95% CI, 1.170–1.208; P < 0.001 and OR, 1.022; 95% CI, 1.005–1.039; P = 0.011) were the predictors of HIS prescription after PCI. Negative stepwise association between an increase in age, based on aged younger than 50 years, and HIS prescription was observed among both previous statin users and nonusers. Most of other comorbidities and concomitant cardiovascular medication use were also negatively associated with a HIS prescription among both populations. There were few differences in positive and negative predictors of HIS prescription after PCI between previous statin users and nonusers.
Table 2.
Patient characteristics as predictors of HIS prescription after PCI
| Previous statin users | Previous statin nonusers | |||||
|---|---|---|---|---|---|---|
| ORa | 95% CI | P value | ORa | 95% CI | P value | |
| Age < 50 | Reference | Reference | ||||
| Age 50–59 | 0.975 | 0.962–0.988 | < 0.001 | 0.986 | 0.973–0.999 | 0.031 |
| Age 60–69 | 0.959 | 0.947–0.971 | < 0.001 | 0.975 | 0.963–0.988 | < 0.001 |
| Age ≥ 70 | 0.933 | 0.922–0.945 | < 0.001 | 0.942 | 0.930–0.954 | < 0.001 |
| Male | 1.009 | 1.003–1.015 | 0.002 | 1.027 | 1.018–1.035 | < 0.001 |
| Hypertension | 0.978 | 0.968–0.988 | < 0.001 | 0.982 | 0.974–0.991 | < 0.001 |
| Diabetes | NA | 0.989 | 0.982–0.997 | 0.005 | ||
| Heart failure | 0.990 | 0.984–0.996 | 0.001 | 0.990 | 0.981–0.998 | 0.017 |
| AF | 0.974 | 0.966–0.983 | < 0.001 | 0.982 | 0.969–0.996 | 0.012 |
| CKD | 0.968 | 0.960–0.977 | < 0.001 | 0.975 | 0.962–0.989 | < 0.001 |
| Malignancy | 0.981 | 0.974–0.988 | < 0.001 | 0.975 | 0.966–0.985 | < 0.001 |
| Indication for PCI | ||||||
| MI | 1.172 | 1.159–1.185 | < 0.001 | 1.189 | 1.170–1.208 | < 0.001 |
| UA | 1.012 | 1.001–1.022 | 0.028 | 1.022 | 1.005–1.039 | 0.011 |
| SA | 0.974 | 0.963–0.984 | < 0.001 | NA | NA | |
| Aspirin | 0.968 | 0.962–0.974 | < 0.001 | 0.977 | 0.968–0.987 | < 0.001 |
| P2Y12 inhibitor | 0.946 | 0.939–0.952 | < 0.001 | 0.967 | 0.952–0.983 | < 0.001 |
| ACE inhibitor | 0.985 | 0.972–0.998 | 0.028 | NA | ||
| ARB | 1.010 | 1.003–1.016 | 0.002 | NA | ||
| BB | 0.975 | 0.968–0.981 | < 0.001 | 0.986 | 0.975–0.998 | 0.025 |
Abbreviations: ACE Angiotensin-converting enzyme, AF Atrial fibrillation, ARB Angiotensin receptor blocker, BB Beta-blocker, CKD Chronic kidney disease, HIS High-intensity statin, MI Myocardial infarction, NA Not applicable, PCI Percutaneous coronary intervention, SA Stable angina, UA Unstable angina
This multivariable analysis was conducted including all the variables showing statistical significance with P value less than 0.05 in univariable analysis
aOdds ratio (OR) of HIS prescription (vs. non-HIS prescription) after PCI
Statin switching before and after percutaneous coronary intervention among previous statin users
Among 115,793 previous statin users, 15,314 were taking HIS prior to index PCI (13.2%) and 100,479 were non-HIS (86.8%). In previous HIS users, 79.1% were continuously prescribed a HIS after PCI, whereas 20.1% received a down-titrated non-HIS. In previous non-HIS users, only 23.8% were prescribed an up-titrated HIS after PCI, whereas 74.8% were continuously treated with non-HIS without adjustment (Table 3). Because non-HIS accounted for a majority of statin used before PCI, trends in statin switching of overall previous statin users were similar to that of previous non-HIS users (Fig. 2). When statin used before PCI was divided by intensity and whether ezetimibe combination, a tendency for repetitive prescription was robust in less intensive statin therapy. While 33.0% and 30.5% of patients who received HIS monotherapy and combination therapy after PCI were taking identical statin before PCI, respectively, 92.7% and 64.1% of those who received non-HIS monotherapy and combination therapy were taking identical statin before PCI, respectively (Additional File 1: Tables S5-S8).
Table 3.
Statin switching before and after PCI among previous Statin users
| Previous HIS users | Previous non-HIS users | Overall | |
|---|---|---|---|
| Unchanged | 12,113 (79.1) | 75,208 (74.8) | 87,321 (75.4) |
| Up-titrated | 23,950 (23.8) | 23,950 (20.7) | |
| Down-titrated | 3081 (20.1) | 3081 (2.7) | |
| Discontinued | 120 (0.8) | 1321 (1.3) | 1441 (1.2) |
| Overall | 15,314 (100) | 100,479 (100) | 115,793 (100) |
Abbreviations:HIS High-intensity statin, PCI Percutaneous coronary intervention
Values are number (%)
Fig. 2.
Switching statin before and after PCI among previous statin users. In previous HIS users, 79.1% were prescribed HIS after PCI, whereas 20.1% received non-HIS. In previous non-HIS users, 23.8% were prescribed HIS after PCI, whereas 74.8% received non-HIS. Statin switching of overall previous statin users were similar to that of previous non-HIS users because non-HIS accounted for a majority of statin used before PCI. Abbreviations: HIS, high-intensity statin; PCI, percutaneous coronary intervention
Association between high-intensity statin prescription and previous statin strategy among previous statin users
Although prescribing of HIS after PCI increased throughout the study period, there was a substantial difference of its percentage according to previous statin use and its intensity. Proportion of patients who received HIS after PCI was 79.1%, 42.0%, and 23.8% in previous HIS users, previous statin nonusers, and previous non-HIS users, respectively, and was 79.7%, 43.9%, and 24.2% when excluding those who did not receive any statin after PCI (Fig. 3). Previous HIS users were more likely to be prescribed a HIS after PCI compared with previous statin nonusers (odds ratio [OR], 5.42; 95% confidence intervals [CI], 4.44–6.61; P < 0.001) and previous non-HIS users (OR, 12.30; 95% CI, 9.95–15.19; P < 0.001) (Table 4). Because previous non-HIS users were less than half as likely as previous statin nonusers to be prescribed a HIS after PCI (OR, 0.44; 95% CI, 0.36–0.53; P < 0.001), overall previous statin users were less likely to be prescribed a HIS than previous statin nonusers (OR, 0.68; 95% CI, 0.57–0.82; P < 0.001). An increase in HIS use after PCI was more rapid in previous statin nonusers than in previous statin users, and the gap in its percentage between the two populations increased from 8.4% in first half of 2014 to 13.2% in second half of 2017 (Additional File 1: Figure S1).
Fig. 3.
Temporal trends of HIS prescription after PCI according to previous statin use and intensity. The figure shows temporal trends in HIS prescription after PCI among previous HIS users, previous non-HIS users, and previous statin nonusers, which were calculated after excluding those who did not receive statin therapy after PCI in each populations. Abbreviations: HIS, high-intensity statin; PCI, percutaneous coronary intervention
Table 4.
Association of previous Statin use and intensity with HIS prescription after PCI
| ORa | 95% CI | P value | |
|---|---|---|---|
| Previous statin use and intensity | |||
| Previous HIS users vs. previous statin nonusers | 5.42 | 4.44–6.61 | < 0.001 |
| Previous HIS users vs. previous non-HIS users | 12.30 | 9.95–15.19 | < 0.001 |
| Previous non-HIS users vs. previous statin nonusers | 0.44 | 0.36–0.53 | < 0.001 |
| Previous statin use | |||
| Previous statin users vs. previous statin nonusers | 0.68 | 0.57–0.82 | < 0.001 |
Abbreviations: HIS High-intensity statin, PCI Percutaneous coronary intervention
aOdds ratio of HIS prescription (vs. non-HIS prescription) after PCI
Discussion
In this retrospective population-based cohort study using medical claims data of more than 200,000 participants, the authors found a number of concerns in statin therapy for secondary prevention after PCI. First, despite guideline recommendations, barely one in third patients were prescribed a HIS within 30 days after hospital discharge for PCI. Second, various patient characteristics were associated with prescribing of HIS after PCI, with few differences between previous statin users and nonusers. Male and patients undergoing PCI for acute coronary syndrome were more likely to be prescribed a HIS after PCI, whereas older patients, female, and those with more comorbidities and cardiovascular medications were less likely to be. These findings were similar to the results of previous observational studies that shown prevalent underuse of statin therapy especially among female, older adults, and patients with comorbid conditions, suggesting that some patient characteristics appeared to cause reluctance for physician to prescribe HIS, which had highest chance for side effects [5, 8, 11]. Third, HIS prescription after PCI was substantially affected by previous statin use and its intensity. The repetitive prescribing of statin without guideline-directed adjustment was widespread in previous statin users, and this may have contributed to increasing gap in HIS use after PCI between previous statin users and nonusers. Given few differences of patient characteristics as positive and negative predictors of HIS prescription between previous statin users and nonusers, the practice of repetitive prescribing may have affected HIS prescription following PCI independently of patient characteristics, suggesting that there may be a negative synergistic effects from patient- and physician-level barriers.
Since the prescription depends on physician’s discretion, therapeutic inertia has been considered a mainly healthcare provider’s failure to achieving optimal clinical outcomes [22, 23, 28, 29]. Nevertheless, previous studies that addressed the underuse of HIS in patients with ASCVD have not discriminated the effect of prescribing practice from that of other barriers such as patient characteristics. We therefore evaluated not only the association of HIS prescription after PCI with previous statin use and its intensity but also the difference of patient characteristics as predictors of HIS prescription following PCI according to previous statin use. Furthermore, to achieve more generalized results, we analyzed the national claims data, not a sample or limited data related to specific physicians, hospitals, or regions. Because we obtained the data from a sole and compulsory insurance system that covers an entire population using single type of service, it appears that there are few chance for missing data or disparities based on region, income status, or insurance type.
Although HIS has been recommended as a first-line strategy in patients with ASCVD for more than a decade, whether guideline implementation has improved over time remains uncertain. Furthermore, how to assess the physician-level barrier and estimate its implications remain unclear. Therefore, we sought to evaluate therapeutic inertia in statin therapy after PCI and identify its predictors that are related to not only patient characteristics but also the prescribing practices. In overall patients, more than six in ten participants did not receive HIS after PCI. Despite few differences of patient characteristics as predictors of HIS prescription, HIS was underused among previous statin users compared with previous statin nonusers, which was attributed to seven in ten previous non-HIS users being prescribed the unchanged statin after PCI. The numerical results may differ by clinical setting; however, this study was conducted to assess the implications of therapeutic and prescription inertia in statin therapy and highlight the need for effort in appropriate medical treatment, not to compare the numerical values across different settings. Our study shows that suboptimal HIS prescription after PCI and different types of physician-level barriers are of remain concerns. Recently, two observational studies demonstrated the efficacy and safety of novel lipid-lowering strategies, a proprotein convertase subtilisin/kexin type 9 inhibitor and inclisiran, in the real-world settings [30, 31]. Given together, appropriate use of ezetimibe or novel lipid-lowering drugs in combination with maximally tolerated statin therapy is essential to provide guideline-directed lipid-lowering therapy and achieve optimal clinical outcomes.
Study limitations
Despite the new findings and strengths, our study has some limitations. First, up-titration of statin more than 30 days after discharge for index PCI was not addressed in the analysis. A previous study reported that there were few patients whose statin was up-titrated within 182 days among those whose statin was not up-titrated within 30 days after discharge for myocardial infarction [8]. Furthermore, a gradual up-titration of statin therapy following PCI contradicted guideline that recommends use HIS for secondary prevention as early as possible. Therefore, we restricted the study duration as of 30 days after discharge for PCI and considered it reasonable to evaluate whether there was a timely intervention within the duration. Second, we used an outdated data from nationwide medical claims since we aimed to assess clinical practice within a restricted time period considering specific guideline and clinical trials. Third, despite the lack of evidence for HIS use for secondary prevention among patients aged over 75 years, we did not separate this cohort from those aged 75 years or younger. Fourth, although NHIS database is one of the largest database that cover more than 50 million people and has been widely used for research, there may be an incorrect information as the data used in this study were extracted from electronic medical claims data. Fifth, owing to inherent limitation of the coding system, the statin-associated side effects comprising with subjective symptoms or requiring laboratory findings and the specific reasons for statin discontinuation among previous statin users were not assessed in this study. Sixth, whether repetitive prescribing of suboptimal statin therapy was potentially affected by patient’s request is unknown. Nonetheless, this is unlikely a major limitation of the study as prescription is finally made by physician’s discretion. Seventh, our study was performed using medical claims data of Republic of Korea based on national insurance and healthcare system during the restricted period. Therefore, the results should be interpreted carefully when extrapolated to other clinical settings
Conclusion
In this nationwide cohort study using large-scale medical claims data in Republic of Korea, HIS therapy for secondary prevention was underused among patients undergoing PCI. Various patient characteristics and physician’s prescribing practice were substantially associated with suboptimal HIS prescription following PCI. The present study emphasizes the need for effort to overcome therapeutic inertia in statin therapy after PCI and provide guideline-directed medical therapy, thereby achieving optimal clinical outcomes.
Supplementary Information
Acknowledgements
Not applicable.
Abbreviations
- ACE
angiotensin-converting enzyme
- AF
atrial fibrillation
- ARB
angiotensin receptor blocker
- ASCVD
atherosclerotic cardiovascular disease
- BB
beta-blocker
- CCB
calcium-channel blocker
- CKD
chronic kidney disease
- HIS
high-intensity statin
- LODESTAR
Low-Density Lipoprotein Cholesterol-Targeting Statin Therapy Versus Intensity-Based Statin Therapy in Patients With Coronary Artery Disease
- MI
myocardial infarction
- NHIS
National Health Insurance Service
- PCI
percutaneous coronary intervention
- RACING
Randomized Comparison of Efficacy and Safety of Lipid-lowering with Statin Monotherapy Versus Statin–ezetimibe Combination for High-risk Cardiovascular Disease
- SA
stable angina
- UA
unstable angina
Authors’ contributions
J-Y.H and Y-H.S conceived and designed the study. J-Y.H, K-H.K, J-H.B, and Y-H.S interpreted and analyzed the data. Y-K.K, K-H.K, and T-G.K wrote the draft of manuscript. J-Y.H, T-G.K, J-H.B, and Y-H.S critically revised the manuscript. All authors read and approved the final manuscript.
Funding
Not applicable.
Data availability
The data that support the findings of this study are available from National Health Insurance Service but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available.
Declarations
Ethics approval and consent to participate
This study was approved by the Institutional Review Board of Konyang University Hospital (2020-04-013) and requirement for written informed consents was waived because this study used anonymized and deidentified data. The study followed the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) reporting guideline and was performed in accordance with the Declaration of Helsinki.
Consent for publication
Not applicable.
Competing interests
The authors declare no competing interests.
Footnotes
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Young-Hoon Seo and Jee-Young Hong contributed equally to this work.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
The data that support the findings of this study are available from National Health Insurance Service but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available.