ROsulord® sAfety for Patients with Dyslipidemia Study: A Non-interventional, Multicenter, Prospective, Observational Study in South Korea

Abstract

Introduction

The ROsulord® sAfety for patients with Dyslipidemia study (ROAD study) in the Republic of Korea investigated the safety and efficacy of rosuvastatin in routine clinical practice.

Methods

This non-interventional, multicenter, prospective, observational study was conducted over a period of approximately 4.6 years and involved 14,243 participants. During this study, we assessed the adverse events, changes in laboratory test results, and efficacy endpoints associated with rosuvastatin use.

Results

The findings revealed a notably low adverse event rate of 1.63%, indicating a favorable safety profile for rosuvastatin in the management of dyslipidemia. Importantly, no clinically significant incidences of statin-associated myopathy, hepatotoxicity, or diabetes were observed during the study period. Moreover, this study demonstrated significant improvements in lipid profiles among patients receiving rosuvastatin treatment, with a reduction in total cholesterol, low-density lipoprotein cholesterol, and triglyceride levels. These improvements contributed to a lower cardiovascular risk in the study population.

Conclusion

Overall, these findings suggest that rosuvastatin is safe and effective in managing dyslipidemia in real-world clinical settings, providing clinicians with valuable insights into the benefits and risks associated with statin therapy in this patient population.

Supplementary Information

The online version contains supplementary material available at 10.1007/s40119-024-00391-4.

Key Summary Points

Why carry out this study?

Dyslipidemia is a major risk factor for cardiovascular disease.

Statins are used to manage 91.8% of patients with dyslipidemia in the Republic of Korea, with the potential for treatment-linked adverse effects.

This study aimed to gather safety information on previously unknown risks of using rosuvastatin for dyslipidemia treatment.

What was learned from this study?

The study showed a low adverse event rate of 1.63%, and no clinically significant incidences of statin-associated myopathy, hepatotoxicity, or diabetes were observed.

This study showed that rosuvastatin is relatively safe and effective in managing dyslipidemia in real-world clinical settings.

Introduction

According to the National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATP III), dyslipidemia is a condition in which low-density lipoprotein cholesterol (LDL-C), triglycerides, or high-density lipoprotein cholesterol (HDL-C) levels are elevated or decreased [1]. Cardiovascular disease is the leading cause of death worldwide, with the World Health Organization reporting that approximately 30% of all global deaths in 2004 were caused by cardiovascular disease. As dyslipidemia is a major risk factor for cardiovascular disease, along with smoking, hypertension, diabetes, and obesity, treating dyslipidemia can significantly reduce cardiovascular mortality [2, 3].

The latest American College of Cardiology (ACC)/American Heart Association (AHA) guidelines, as well as the 2022 Korean Dyslipidemia Guidelines, recommend statins as the first-line treatment for dyslipidemia [4–6]. The ACC/AHA guidelines also provide detailed dosing criteria and policies for statin use, not only for the treatment of dyslipidemia but also for primary and secondary prevention of atherosclerotic cardiovascular disease [4]. Moreover, according to the Dyslipidemia Fact Sheet published in 2020, statins have been used to treat 91.8% of patients with dyslipidemia in the Republic of Korea (further referred to as Korea) [7]. Clinical studies, conducted in various patient groups, with and without vascular diseases and dyslipidemia, have shown that statins are highly effective in improving lipid metabolism and preventing cardiovascular diseases. Large primary prevention studies, such as WOSCOPS and AFCAPS/TexCAPS, have demonstrated reductions in major coronary events and cardiovascular mortality, and the IMPROVE-IT and TIMI22 studies have shown that aggressive lipid-lowering therapy with high-dose statins is effective in preventing cardiovascular events in ultra-high-risk patients with acute coronary syndrome [8]. However, several adverse events (AEs), including hepatotoxicity, myopathy, acute renal failure, and cataracts, have been associated with the dose, duration of use, patient comorbidities, concomitant medications, and termination of statin use, although these are often transient and reversible upon discontinuation [9].

Among the statin-induced AEs, myopathy is the least common, with an incidence rate of 0.1–0.01%, but it is often the most important reason for discontinuation. Its presentation is highly variable, ranging from mild myalgia to rare but life-threatening rhabdomyolysis; thus, statin use requires caution, especially when the drug is administered to the elderly who are often underweight or have renal failure, hypothyroidism, or alcoholism [10, 11].

The number of patients with dyslipidemia continues to increase in the Respublic of Korea (Korea), with a prevalence rate of 38.4% in 2018 [6], and the number of patients exposed to statin drugs is expected to increase owing to the nature of the disease and long-term use of statin drugs. Therefore, we conducted this study to gather safety information on previously unknown risks, including myopathy, the most important AE reported as a reason for discontinuing statin medication in routine practice, in patients with various comorbidities. The aim of this ROsulord® sAfety for patients with Dyslipidemia study (ROAD study) in Korea was to investigate the safety and efficacy of the statin rosuvastatin in routine clinical practice.

Methods

Patients and Study Design

The ROAD study was a non-interventional, multicenter, prospective, observational study conducted at 311 sites in Korea over a period of approximately 4.6 years, from August 2015 to February 2020. The inclusion criteria were a dyslipidemia diagnosis, age ≥ 19 years, capability to take Rosulord® (Chong Kun Dang Pharmaceutical Corporation, Seoul, Korea), and provision of written informed consent to participate in the study. The exclusion criteria were pregnancy or planning to become pregnant (within 12 months); nursing/breast-feeding; known hypersensitivity to any of the drug components; active liver disease, including persistent serum transaminases of unknown cause or serum transaminase levels > 3-fold the upper limit of normal; myopathy; concomitant use of cyclosporine; and severe renal impairment (creatinine clearance [CLcr] < 30 mL/min).

Patients who met the inclusion criteria were consecutively enrolled and received rosuvastatin as part of routine clinical care, without any experimental interventions. Their data were recorded in an electronic case report form. The dose and duration of treatment were adjusted at the discretion of the investigator according to the patient’s condition, based on the approved labeling of Rosulord. The observation period for each patient was approximately 12 ± 4 weeks, with the baseline (day 0, visit 1) defined as the day after enrollment when the patient’s data were first collected and the prescription for Rosulord was initiated, followed by a follow-up visit (visit 2) at 12 ± 4 weeks.

The label for rosuvastatin states that it has musculoskeletal effects [12]. Therefore, we used the results of the JUPITER study (2008–2016), which involved CRESTOR (AstraZeneca Pharmaceuticals, Wilmington, DE, USA), a rosuvastatin-containing drug, to calculate the number of participants for the ROAD study. In the JUPITER study, myopathy occurred in ten of 8869 patients (0.112%) treated with rosuvastatin. Therefore, we assumed an incidence rate of 0.112% and a margin of error of 0.056%, which is 50% of the incidence rate, with a two-sided significance level of 0.05, resulting in a study population of 13,705 patients. Taking a dropout rate of 2% into consideration, a study population of 13,985 patients was required. Therefore, to conduct our rosuvastatin safety study, we included more than the minimum number of patients (N = 14,259) with dyslipidemia.

The ROAD study was an observational study that was conducted in local clinics and general hospitals. Approval for the study was provided by the respective Institutional Review Boards (IRBs) of institutions with IRBs (Kyung Hee University Hospital IRB No: 2015-11-304). This study was conducted in accordance with the Helsinki Declaration of 1964 and its later amendments. All participants provided written informed consent to participate in the study. An Independent Data Monitoring Committee (IDMC) was responsible for monitoring both data integrity and drug safety throughout the study.

Outcome Measures

Among patients who met the inclusion and exclusion criteria and received Rosulord, the safety endpoints were the incidence of all AEs during treatment and changes in other laboratory tests measured before and after treatment with Rosulord. All AEs occurring during treatment with Rosulord were studied. The signs or symptoms of the condition or disease caused by Rosulord were recorded as AEs only if there was a significant change in the nature of the event or a clinically significant increase in frequency or severity compared to the investigator's clinical profile based on the patient’s past and present medical history or baseline. AEs were coded using the Medical Dictionary for Regulatory Activities (MedDRA) V17.1.

A serious AE (SAE) is considered to be an AE resulting in any of the following outcomes: death, a life-threatening condition, inpatient hospitalization or prolongation of existing hospitalization, significant or permanent disability/incapacity, a congenital anomaly/birth defect, or other serious important medical events. The severity of an AE, in comparison, refers to the intensity of the event and is classified as mild, moderate, or severe. Severity is assessed based on the impact of the event on the patient’s daily activities, with mild referring to easily tolerated symptoms, moderate indicating symptoms that interfere with normal activities, and severe denoting symptoms that are incapacitating and prevent the patient from performing normal activities. SAEs also include any other event that investigators or sponsors consider to be of significant medical concern. A serious adverse drug reaction (SADR) is a SAE for which a causal relationship with the investigational drug cannot be excluded. In the ROAD study, an unexpected AE was an AE whose nature, severity, or frequency differed from what is known from the Rosulord label, and an unexpected SADR (USADR) was considered to be a SAE due to Rosulord use that occurred unexpectedly based on the product’s label.

To assess the efficacy of rosuvastatin, we measured the proportion of patients who reached target levels of LDL-C (< 100 mg/dL for high-risk groups, < 70 mg/dL for very high-risk groups) and non-HDL-C (< 130 mg/dL for high-risk groups, < 100 mg/dL for very high-risk groups) and categorized them into the very-high- and high-risk dyslipidemia groups. According to the 2018 Korean Guidelines for the Management of Dyslipidemia, patients with a history of cardiovascular diseases, such as coronary artery disease, peripheral artery disease, or ischemic stroke, are classified as being very-high-risk groups, while those with a history of aortic aneurysm, carotid artery stenosis, or diabetes mellitus are categorized as high-risk groups. Additionally, we analyzed the percentage change in serum lipid levels from baseline to after rosuvastatin treatment. We conducted a sub-analysis of the new patient status, defined as patients with a dyslipidemia diagnosis within 3 months of the Rosulord start date.

Statistical Analysis

Data requiring descriptive statistics are presented as the number of patients, mean, standard deviation (SD), median, minimum (min), and maximum (max). Categorical data are presented as the number of patients and percentage. The paired t-test or Wilcoxon signed-rank test was used to analyze comparisons between baseline and visit 2, and the Kruskal–Wallis test was used to analyze comparisons between age groups. All statistical analyses were performed using the SAS software package Ver. 9.4 (SAS Institute Inc. , Cary, NC, USA), with a significance level (α) of 0.05.

Results

Population

Of the 14,259 patients selected, 16 patients were excluded from the safety evaluation (3 due to data redundancy and 13 due to not meeting the inclusion criteria). Of the 14,243 patients included in the safety evaluation, 9838 patients were excluded from the efficacy evaluation due to lack of relevant data, and 4405 patients were analyzed for efficacy (Fig. 1).

Fig. 1.

Study flow chart. CRF case report form

The demographic characteristics of the participants are presented in Table 1. Of the 14,243 patients, 6629 (46.54%) were men and 7614 (53.46%) were women. The mean (± SD) age was 60.73 ± 11.89 years, with 11,820 (82.98%) aged ≥ 50 years, 8988 (63.10%) aged < 65 years, and 5255 (36.90%) aged ≥ 65 years. No allergies were reported by 14,178 (99.54%) patients, current smoking was reported by 2469 (17.33%) patients, and current alcohol consumption was reported by 4327 (30.38%) patient. The average (± SD) weight and height were 65.67 ± 11.52 kg and 162.49 ± 9.06 cm, respectively. In total, 5011 (35.18%) participants had hypertension, 2304 (16.18%) had diabetes, 140 (0.98%) had coronary artery disease, and 2297 (16.13%) had dyslipidemia.

Table 1.

Baseline characteristics of the study population

Variable	N = 14,243 patients
Sex
Male, n (%)	6629 (46.54)
Female, n (%)	7614 (53.46)
Age (years)
n	14,243
Mean ± SD	60.73 ± 11.89
Median	60
Min, max	19.00, 99.00
Age category, n (%)
19–29 years	55 (0.39)
30–39 years	494 (3.47)
40–49 years	1874 (13.16)
50–59 years	4273 (30.00)
60–69 years	4124 (28.95)
≥ 70 years	3423 (24.03)
Elderly, n (%)
< 65 years	8988 (63.10)
≥ 65 years	5255 (36.90)
Allergy, n (%)
Yes	65 (0.46)
No	14,178 (99.54)
Smoking, n (%)
Past smoking	1210 (8.50)
Currently smoking	2469 (17.33)
Non-smoker	10,564 (74.17)
Drinking, n (%)
Past drinking	889 (6.24)
Current drinking	4327 (30.38)
Non-drinking	9027 (63.38)
Weight (kg)
n	4007
Mean ± SD	65.67 ± 11.52
Median	65
Min, max	33.00–134.00
n	3913
Height (cm)
Mean ± SD	162.49 ± 9.06
Median	162
Min, max	110.00–189.00
BMI (kg/m)2
n	3863
Mean ± SD	24.82 ± 3.32
Median	24.56
Min, max	14.36–66.12
SBP (mmHg)
n	6683
Mean ± SD	129.31 ± 13.44
Median	130
Min, max	75.00–210.00
DBP (mmHg)
n	6683
Mean ± SD	78.97 ± 10.10
Median	80
Min, max	38.00–139.00
Duration of dyslipidemia (years)
n	14,243
Mean ± SD	2.45 ± 3.54
Median	1.04
Min, max	0.00a–31.94
Duration of dyslipidemia category, n (%)
<1 year	7001 (49.15)
< 1–3 years	3262 (22.90)
< 3–6 years	2096 (14.72)
< 6–10 years	1204 (8.45)
> 10 years	680 (4.77)
Hypertension, n (%)
Yes	5011 (35.18)
No	9232 (64.82)
Diabetes mellitus, n (%)
Yes	2304 (16.18)
No	11,939 (83.82)
Coronary artery disease, n (%)
Yes	140 (0.98)
No	14,103 (99.02)
New patientbor not, n (%)
Yes	2297 (16.13)
No	11,946 (83.87)

BMI body mass index, DBP diastolic blood pressure, SBP systolic blood pressure, SD standard deviation

^a3311 subjects with the duration of dyslipidemia < 0.01 year

^bDiagnosis date is within 3 months of the start date of Rosulord

The administration status of Rosulord® is presented in Electronic Supplementary Material (ESM) Table S1. The average duration of administration was 88.15 ± 52.22 days, with a median of 91 days and a range of 1 to 1532 days. The most common dosage administered was 10 mg, taken by 9155 patients (64.28%), followed by 5 mg in 4241 patients (29.78%), and 20 mg in 781 patients (5.48%). Dosage adjustments occurred in a small proportion of patients, with 66 patients (0.46%) adjusting their dose due to symptom management. The primary reasons for discontinuation were follow-up failure (649 patients; 4.56%), withdrawal of consent (83 patients; 0.58%), and AEs (45 patients; 0.32%). Additionally, 295 patients (2.07%) discontinued due to study completion.

Safety Outcomes

Among the 14,243 patients studied, 232 (1.63%) reported incidences, and 296 AEs were observed. Of these, 37 patients (0.26%, 40 events) had confirmed AEs that could not be excluded as causally related to rosuvastatin, 14 patients (0.10%, 17 events) had SAEs, and one patient (0.01%) had a SADR. Among all patients, 140 (0.98%) experienced 164 unexpected events (i.e., those not listed in the product label), nine (0.06%, 9 events) experienced unexpected AEs, and 12 (0.08%, 14 events) experienced unexpected SAEs (Table 2).

Table 2.

Summary of adverse events

Adverse events	Patients (N = 14,243)
	Incidence rate, n (%)	95% confidence interval (lower, upper limit)	Number of events
Adverse eventsa	232 (1.63)	(1.42, 1.84)	296
Adverse drug reactionsb	37 (0.26)	(0.18, 0.34)	40
Serious adverse eventsc	14 (0.10)	(0.05, 0.15)	17
Serious adverse drug reactionsd	1 (0.01)	(0.00, 0.02)	1
Unexpected adverse eventse	140 (0.98)	(0.82, 1.14)	164
Unexpected adverse drug reactionsf	9 (0.06)	(0.02, 0.10)	9
Unexpected serious adverse drug reactionsg	12 (0.08)	(0.04,0.13)	14

^aAny undesirable experience or unintended effect that occurs in a patient during this study, regardless of whether it is related to Rosulord

^bAn adverse event where a causal relationship with Rosulord cannot be excluded

^cAn adverse event that falls into categories such as death, a life-threatening condition, inpatient hospitalization or prolongation of existing hospitalization, significant or permanent disability/incapacity, or a congenital anomaly/birth defect. It also includes any other event considered by investigators or sponsors to be of significant medical concern

^dA serious adverse event where a causal relationship with Rosulord cannot be excluded

^eAn adverse event whose nature, severity, or frequency differs from what is known from the Rosulord label

^fAn adverse drug reaction whose nature, severity, or frequency differs from what is known from the Rosulord label

^gA serious adverse drug reaction to the investigational drug that occurs unexpectedly based on the Rosulord label

When the 14 SAEs classified by the System Organ Class (SOC) using MedDRA version 17.1, the SOC class “infections and infestations” accounted for four patients (0.03%, 4 events), SOC class “gastrointestinal disorders,” for three patients (0.02%, 4 events); SOC class ”musculoskeletal and connective tissue disorders” and “nervous system disorders,” for two patients each (0.01%, 2 events); and SOC class “cardiac disorders, “general disorders and administration site conditions,” “hepatobiliary disorders,” “metabolism and nutrition disorders,” and “psychiatric disorders,” for one patient each (0.01%, 1 event). For the SADRs, one (0.01%, 1 event) patient was classified as having “general disorders and administration site conditions” (ESM Table S2).

Myopathy cases, which were carefully noted during the study, included 11 cases of known myalgia (0.08%, 11 ADRs), three cases of musculoskeletal pain (0.02%, 1 ADR), one case of increased blood creatine phosphokinase (0.01%, 1 ADR), one case of muscular weakness (0.01%, 1 ADR), and one case of myofascial pain syndrome (0.01%, 0 ADR) (ESM Table S2). The relevant laboratory tests (creatinine kinase [CK]) showed a slight increase in the mean value (2.77 mg/dL) after 12 weeks of treatment, compared to baseline; the change was not statistically significant (Table 3).

Table 3.

Changes in laboratory variables after Rosulord treatment

Variable	Time point	n	Mean	Standard deviation	Median	Minimum	Maximum	p valuea
HbA1c	Baseline	424	7.36	1.48	7.00	5.00	14.80
	Visit 2	424	6.91	1.09	6.90	4.90	15.90
	Change	424	− 0.44	1.22	− 0.10	− 9.10	2.60	< 0.0001
ALT (SGPT)	Baseline	1012	26.05	14.41	23.00	7.00	163.00
	Visit 2	1012	25.81	13.63	23.00	7.00	188.00
	Change	1012	− 0.24	13.90	0.00	− 139.00	160.00	0.5892
AST (SGOT)	Baseline	1012	27.53	14.25	25.00	8.00	288.00
	Visit 2	1012	27.39	11.74	26.00	7.00	158.00
	Change	1012	− 0.13	13.58	0.00	− 232.00	133.00	0.7522
CK	Baseline	112	101.96	84.20	87.00	0.60	549.00
	Visit 2	112	104.73	72.93	91.00	0.70	446.00
	Change	112	2.77	79.78	3.00	− 417.00	308.00	0.7140

ALT Alanine transaminase, AST aspartate aminotransferase, CK creatinine kinase, HbA1c glycated hemoglobin, SGOT serum glutamic-oxaloacetic transaminase, SGPT serum glutamic-pyruvic transaminase

^aPaired t-test results for change in each laboratory variable from baseline to visit 2

In terms of hepatotoxicity, aspartate aminotransferase (AST) levels increased in six patients (0.04%, 5 ADRs), alanine transaminase (ALT) levels increased in three patients (0.02%, 2 ADRs), liver disorder was observed in two patients (0.01%, 0 ADRs), and abnormal liver function was noted in one1 patient (0.01%, 0 ADRs) (ESM Table S3). Relevant laboratory tests showed a slight decrease in the mean values of AST and ALT after 12 weeks of treatment, compared to baseline, but the decrease was not statistically significant (Table 3).

There were no new cases of diabetes during the study, one case of increased glycated hemoglobin (HbA1c; 0.01%, 1 ADR), and a non-significant decrease in HbA1c from baseline to 12 weeks post-dose, from a mean of 7.36–6.91% (Table 3; ESM Table S3).

The majority of these AEs were mild, with one case each of a severe increase in AST, ALT, blood CK, and HbA1c and one case each of moderate myalgia, musculoskeletal pain, myofascial pain syndrome, and abnormal liver function test results, with 93.33% of patients recovered or in recovery and no serious AEs.

Efficacy Outcomes

Analysis of the percent change in the serum lipid profile from baseline to post-treatment with Rosulord showed that from baseline to 12 weeks of treatment, total mean (± SD) cholesterol decreased from 217.09 ± 52.50 to 166.23 ± 36.80 mg/dL (− 20.63%), LDL-C decreased from 134.89 ± 47.18 to 90.02 ± 31.81 mg/dL (− 27.17%), and triglycerides decreased from 166.22 ± 98.55 to 138.83 ± 82.99 mg/dL (− 5.21%); all decreases were statistically significant at p < 0.0001. When LDL-C data were divided into new and old patients, the change rate from baseline to 12 weeks after treatment was − 36.01 ± 29.01% in new patients and − 24.8 ± 29.97% in old patients, and the difference between the two groups was statistically significant (p < 0.0001) (Fig. 2).

Fig. 2.

Lipid profile change after rosuvastatin treatment. a Change in lipid profile change, b changes in LDL-C based on new patient status. Single asterisk (*) indicates significant percent change in each test result from baseline to visit 2 according to the paired t-test. Double asterisk (**) indicate significant change in LDL-C from baseline to visit 2 in new and old patients according to the Wilcoxon rank sum test. HDL High-density lipid, LDL low-density lipid, LDL-C LDL-cholesterol

In this study, the medical history was collected according to the risk factors suggested in the 4th edition of the Guidelines for the Treatment of Dyslipidemia published in 2018 by the Guidelines Committee of the Korean Society of Lipid and Atherosclerosis [13]. The rate of reaching the target LDL-C or non-HDL-C level was analyzed by categorizing the patients into ultra-high- and high-risk groups. Of the 343 patients in the very-high-risk group, the proportions of patients who achieved the target LDL-C levels (< 70 mg/dL), target non-HDL-C levels (< 100 mg/dL), and target LDL-C or non-HDL-C levels were 53.64% (184 patients), 67.35% (231 patients), and 69.68% (239 patients), respectively. Of the 953 patients in the high-risk group, the proportions of patients achieving the target LDL-C level (< 100 mg/dL), target non-HDL-C level (< 130 mg/dL), and target LDL-C or non-HDL-C were 70.72% (674), 74.08% (706 participants), and 76.50% (729 participants), respectively. Thus, all three dyslipidemia treatment goals were more likely to be achieved in the lower-risk strata than in the very high-risk strata (Fig. 3).

Fig. 3.

Target LDL-C and non-HDL-C attainment rates by cardiovascular risk group. a LDL-C and non-HDL-C goal achievement rate in the very high-risk group. b LDL-C and non-HDL-C goal achievement rate in the high-risk group. HDL-C High-density lipid cholesterol, LDL-C low-density lipid-cholesterol,

Discussion

We conducted a safety study of rosuvastatin in 14,243 patients with dyslipidemia to collect safety information, including AEs that may occur after the drug was marketed. During this safety study, AEs were reported in 232 (1.63%) patients, accounting for a total of 296 events among the 14,243 patients evaluated for safety; this rate is lower than the post-marketing surveillance results described in the package insert (310, 10.06%). However, the ranking of events reported as AEs and adverse reactions tended to be similar, and myalgia, increased AST, and increased ALT were reported more frequently as AEs.

AEs and the laboratory test results for HbA1c, ALT, AST, and CK were collected to evaluate the safety of rosuvastatin in relation to published clinical studies on statins that showed an increased risk of diabetes [14], hepatotoxicity, and myotoxicity [13], which are rare but potentially fatal AEs. We noted no case of new-onset diabetes or decrease in HbA1c after 12 weeks of treatment compared to baseline, and no patients developed severe myalgia or myopathy, although mild-to-moderate muscle-related AEs were reported. Hepatotoxicity-related AEs mainly consisted of elevations in AST and ALT levels, but the incidence of such increases was not high compared to that in previous studies or the product label, and the mean test values decreased slightly from baseline.

Overall, no major AEs were observed in this study population. However, among the unexpected AEs, i.e., AEs not reported in previous studies (licensure studies and regulatory post-marketing surveillance), dyspepsia was reported in nine patients (0.06%), which is a relatively high frequency of AEs; moreover, three patients were evaluated for ADRs, which may warrant further study.

When analyzing the percent change in serum lipids from baseline to post-treatment, statistically significant decreases in total cholesterol, LDL-C, and triglycerides were observed after 12 weeks of treatment, compared to baseline (all p < 0.0001), indicating significant lipid improvements.

When ultra-high- and high-risk patients were stratified by cardiovascular risk to determine the target LDL-C or non-HDL-C level attainment, two dyslipidemia treatment targets were higher in the lower-risk strata than in the higher-risk strata. An increased risk lowers the target level, which leads to the lower rate of target attainment. When compared to the treatment goal attainment rates in a retrospective observational study of 2000 Korean patients with dyslipidemia, albeit in a diabetic population, the trends were similar: 55.2% and 34.9% patients in ultra-high-risk groups I and II, respectively, and 72.6% in the high-risk group [15].

The goal of dyslipidemia treatment is to reduce cardiovascular risk and ultimately mortality [16]. Therefore, a reduction in cardiovascular risk after treatment is very important. In this study, we analyzed the 10-year risk of atherosclerotic cardiovascular disease (ASCVD) before and after treatment with Rosulord. A statistically significant reduction in risk was observed, suggesting that Rosulord was effective in treating dyslipidemia, resulting in a lower cardiovascular risk.

There are a number of limitations to this study. First, there was a lack of follow-up. The patients were not followed up for an extended period, thereby limiting our ability to interpret whether this effect could be sustained in the long term, beyond the initial 12 weeks. Also, only 30% of the total enrolled patients were included in the efficacy set. This reduction is an inherent characteristic of non-interventional, observational studies, in which a significant proportion of patients may not have follow-up visits or may lack key efficacy endpoint data at the predetermined time points. Additionally, we cannot rule out that the reported incidence of AEs may be lower than that reported in interventional studies, owing to the passive collection of safety information. Future studies with more comprehensive data on the long-term safety and efficacy of rosuvastatin are needed to better understand its sustained impact and to address the limitations observed in this study.

Conclusion

This study is significant as it constitutes a large-scale real-world investigation involving Asian patients. In patients with dyslipidemia, 12 weeks of rosuvastatin treatment was associated with a very low AE rate of 1.63%, with no clinically significant risk of statin-associated myopathy, hepatotoxicity, or diabetes. In addition, analyses of efficacy outcomes in the pooled population showed improvements in total cholesterol, LDL-C, triglyceride, and cardiovascular risk from baseline to post-treatment with rosuvastatin, suggesting that rosuvastatin is a safe and useful treatment for patients with dyslipidemia.

Supplementary Information

Below is the link to the electronic supplementary material.

Author Contributions

Do Young Kim, Sung Hea Kim, Eung-Ju Kim, Sang-Jin Han, Ji-Yeong Park, Jong- Chan Youn, Kyu-Hyung Ryu, Hee-Seok Kim, and Ji-Eun Jeong contributed to the study conception and design, material preparation, data collection, and analysis. All authors reviewed, commented on previous versions, and approved the final manuscript. The corresponding author, Kyu-Hyung Ryu, is the chair of the IDMC and supervised the entire writing process.

Funding

This study was sponsored by the Chong Kun Dang Pharmacy Corporation (Seoul, Korea), who funded the journal’s Rapid Service Fee. The funding source was not involved in the interpretation of data, writing of the report, or decision to submit the article for publication.

Data Availability

The data presented in this article cannot be shared publicly, to uphold the privacy of the study participants. The data will be shared by the corresponding authors upon reasonable request.

Declarations

Conflict of Interest

Do Young Kim, Sung Hea Kim, Eung-Ju Kim, Sang-Jin Han, Ji-Yeong Park, Jong- Chan Youn, Kyu-Hyung Ryu, Hee-Seok Kim, and Ji-Eun Jeong declare that they have no competing interests.

Ethical Approval

The ROAD study was an observational study that was conducted in local clinics and general hospitals. Approval for the study was provided by the respective Institutional Review Boards (IRBs) of institutions with IRBs (Kyung Hee University Hospital IRB No: 2015-11-304). This study was conducted in accordance with the Helsinki Declaration of 1964 and its later amendments. All participants provided written informed consent to participate in the study. An Independent Data Monitoring Committee (IDMC) was responsible for monitoring both data integrity and drug safety throughout the study.