Article ID: CJ-23-0814
Background: Real-world utilization data for evolocumab, the first proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor to be introduced in Japan in 2016, to date are limited. This study aimed to clarify the current real-world patient user profiles of evolocumab based on large-scale health claims data.
Methods and Results: This retrospective database study examined patients from a health administrative database (MDV database) who initiated evolocumab between April 2016 (baseline) and November 2021. Characteristics and clinical profiles of this patient population are described. In all, 4,022 patients were included in the final analysis. Most evolocumab prescriptions occurred in the outpatient setting (3,170; 78.82%), and 940 patients (23.37%) had a recent diagnosis of familial hypercholesterolemia. Common recent atherosclerotic cardiovascular disease events at baseline included myocardial infarction (1,633; 40.60%), unstable angina (561; 13.95%), and ischemic stroke (408; 10.14%). Comorbidity diseases included hypertension (2,504; 62.26%), heart failure (1,750; 43.51%), diabetes (1,199; 29.81%), and chronic kidney disease (297; 7.38%). Among the lipid-lowering regimens concomitant with evolocumab, ezetimibe+statin was used most frequently (1,281; 31.85%), followed by no concomitant lipid-lowering regimen (1,190; 29.59%), statin (950; 23.62%), and ezetimibe (601; 14.94%). The median evolocumab treatment duration for all patients was 260 days (interquartile range 57–575 days).
Conclusions: This study provides real-world insights into evolocumab utilization in Japan for optimizing patient care and adherence to guideline-based therapies to better address hypercholesterolemia in Japan.
Hypercholesterolemia is an independent risk factor for atherosclerotic cardiovascular disease (ASCVD).1 Globally, there were 4.4 million deaths (95% confidence interval [CI] 3.3–5.7 million) attributable to high levels of low-density lipoprotein cholesterol (LDL-C) in 2019, an increase of 46.7% compared with mortality in 1990.2 Global guidelines for hypercholesterolemia and the secondary prevention of ASCVD emphasize specific LDL-C targets and appropriate statin intensity for reducing LDL-C levels, as well as recommended use of non-statin lipid-lowering regimens.3
In Japan, hypercholesterolemia has become a serious health concern as the population rapidly ages and lifestyles change. According to the Japan National Health and Nutrition Survey 2019, the mean LDL-C concentration in men and women aged ≥20 years was 116.8 and 122.6 mg/dL, respectively.4 Less than 25% of survey respondents reported using lipid-lowering therapies and LDL-C concentrations ≥130 mg/dL were observed in 32.0% of men and 38.8% of women.4 The 2022 Japan Atherosclerosis Society (JAS) guidelines recommend lowering LDL-C to <70 mg/dL for secondary prevention among high-risk patients (e.g., patients with familial hypercholesterolemia [FH], acute coronary syndrome [ACS], cerebral infarction, or diabetes).5 However, the Evolocumab (AMG 145), a Monoclonal Antibody to PCSK9, Significantly Reduces Lipoprotein(a) in Hypercholesterolemic Patients Receiving Statin Therapy: An Analysis From the Phase 3, Randomized, Double-blind, Placebo-controlled Study in Japan (EXPLORE-J) study of patients hospitalized with ACS in Japan observed that only 35% of patients achieved this target by relying on statin and ezetimibe over 2 years of follow up.6 Lipid management in Japan requires further optimization, suggesting a potential expanded role for non-statin lipid-lowering therapies.
Evolocumab is a first-in-class monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9) function and has shown promising results in international studies.7 A meta-analysis of multiple large trials supports PCSK9 inhibitors (PCSK9i) as one of the most effective lipid-lowering treatments in reducing LDL-C as well as the associated relative risk (RR) of major vascular events (RR 0.49; 95% CI 0.34–0.71).8 In the Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk (FOURIER) trial, treatment with evolocumab significantly reduced the risk of cardiovascular death, myocardial infarction, or stroke by reducing LDL-C by a median of 30 mg/dL.9 Evolocumab reduced LDL-C by a mean (±SD) of 58.0±19.1% in Open Label Study of Long Term Evaluation against LDL-C (OSLER)-1 and 62.7±25.6% in OSLER-2, two 5-year open-label extension studies in Japan.10 A previous trial also demonstrated superior reduction of LDL-C by evolocumab compared with ezetimibe in Japanese patients with statin intolerance.11 Global and Japanese treatment guidelines have used this evidence base to recommend PCSK9i, like evolocumab, for ASCVD secondary prevention and FH lipid management after maximized tolerated statin treatment.5,12,13
Unlike in Europe,14 large-scale real-world data have rarely been used to assess PCSK9i utilization in Japan. There is an unmet need to understand patient characteristics, such as concomitant disease and treatment, and explore the gap between guidelines and real-world practice. Insights into the utilization of evolocumab may help refine LDL-C management strategies and help shape future guidelines and healthcare policies, ensuring appropriate patient access.
This is a retrospective database study of an administrative health claims database in Japan. The MDV database (Medical Data Vision Co. Ltd.) is an anonymized database of hospital-based health claims and diagnosis procedure combination (DPC) data covering 36 million patients in Japan.15 The database contains inpatient and outpatient medical care data from approximately 25% of 440 acute-care hospitals across Japan. The database can be used to follow patients over time within the same institution and contains patient-level information on demographics, clinical diagnoses (International Classifications of Diseases [ICD]-10 version 2013), procedures, prescriptions, and laboratory test values (available from ~10% of participating hospitals).
Only patients who had at least one record of evolocumab and were aged ≥15 years on the date of initial evolocumab treatment were included. The patients included in the study mainly complied with the efficacy and dosage regimen within the approved Japanese evolocumab package insert. The study period was from April 22, 2014 to November 30, 2021, inclusive. Within this study period, the identification period was from April 21, 2016 to November 30, 2021, and the index date was the first date of evolocumab prescription during the identification period. The study design schema is shown in Figure 1, with 6 months and 1 and 2 years of baseline data for obtaining baseline characteristics, laboratory values, and previous ACS events, respectively.
Schema showing the study design.
We defined the treatment duration for evolocumab based on the dispensing records. The end date of treatment was marked as the day the last prescription’s supply was depleted, considering the days covered by the last prescription. Specifically, a syringe or pen of evolocumab (140 mg) was accounted for as covering 14 days, and the auto mini-doser (AMD; 420 mg) as covering 28 days. Discontinuation was identified if there was a failure to dispense a new evolocumab prescription within 60 days following the exhaustion of the previous supply. In calculating treatment duration, any gaps in medication less than 60 days were included, whereas overlaps in prescriptions were not double counted nor extended to modify treatment gaps. Our analysis focused solely on the first continuous treatment duration.
Only the statin prescription closest to index date during the baseline period (i.e., before evolocumab use) or the statin prescription closest to or on index date during the initial evolocumab treatment (i.e., concomitant use) were considered to define regimen categorization. For lipid-lowering regimens concomitant with evolocumab, only prescriptions within the treatment duration of evolocumab prior to discontinuation date were considered. Patients who had no baseline period (i.e., did not have a claim during the prior 6 months) were analyzed only for lipid-lowering therapy on the date of initial evolocumab use. Statin intensity level was assessed according to international guidelines.12 Prior ACS events were defined as acute myocardial infarction, subsequent myocardial infarction, ACS or unstable angina for main disease requiring emergency hospitalization.
The patient characteristics that described the clinical profiles of patients included a recent diagnosis of concomitant ASCVD, recently diagnosed chronic comorbid disease, baseline comedications, comedications prescribed with evolocumab at initial prescription, baseline laboratory data, and hospital size (≥200 vs. <200 beds vs. clinic [<20 beds]).
In addition, time-to-event analysis was applied for time to the discontinuation of the patients’ first continuous treatment. Kaplan-Meier (KM) estimation of the life table was used, where an event was defined as the first discontinuation of evolocumab (i.e., all patients will eventually have an event) and the time indicator was defined as time to discontinuation. The KM median, 95% CI, and KM plot were produced for the main cohort and all subgroups.
All outcomes were described with aggregate and subgroup analysis. All descriptive variables are described with summary statistics: mean±SD, median with interquartile range, and the minimum and maximum for continuous variables; numbers and percentages for categorical variables. The denominator of the presented proportions was the entire patient cohort unless stated otherwise. Observations with missing values in a variable were omitted in the calculation of the descriptive statistics for the variable unless stated otherwise. All analyses were performed in a manner consistent with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines and applicable sections of the Reporting of studies Conducted using Observational Routinely collected health Data (RECORD).16,17 Statistical testing was not performed, and all analyses were completed using SAS v9.4.
There were 4,022 patients who met all the inclusion criteria. The mean age at evolocumab initiation was 63.94±12.95 years (Table 1). There were 1,852 (46.05%) patients who were aged <65 years and 2,170 (53.95%) who were aged ≥65 years, and most patients were male (2,734; 67.98%). Antiplatelet agents (2,824; 70.21%) and anti-anginal agents (2,435; 60.54%) were used in a high proportion of patients.
Characteristics of Patients Initiating Evolocumab (n=4,022)
| Age at evolocumab initiation (years) | |
| Mean (±SD) | 63.94±12.95 |
| Median [IQR] | 66.00 [55.00–74.00] |
| Minimum–maximum | 16.00–98.00 |
| <65 years | 1,852 (46.05) |
| ≥65 years | 2,170 (53.95) |
| Sex | |
| Female | 1,288 (32.02) |
| Male | 2,734 (67.98) |
| Concomitant disease | |
| ACS: overall | 1,173 (29.16) |
| AMI | 619 (16.91) |
| Unstable angina | 561 (13.95) |
| Other acute ischemic heart diseases | 91 (2.26) |
| Cerebral infarction: overall | 402 (10.00) |
| Atherosclerotic type | 119 (2.96) |
| Non-atherosclerotic type | 201 (5.00) |
| Other | 82 (2.04) |
| PAD | 283 (7.04) |
| Comorbid disease | |
| Hypertension | 2,504 (62.26) |
| Heart failure | 1,750 (43.51) |
| Diabetes | 1,199 (29.81) |
| FH | 940 (23.37) |
| CKD | 297 (7.38) |
| Recent medical procedures | |
| Coronary revascularization | 1,163 (28.92) |
| LDL apheresis | 36 (0.90) |
| Past PCI | |
| Beyond 6 months | 824 (20.49) |
| Within 6 months | 1,184 (29.44) |
| ACS event within 2 years | |
| No. patients | 850 (21.10) |
| Days from last event to index date | |
| Mean (±SD) | 168.07±186.87 |
| Median [IQR] | 82 [20.00–277.00] |
| Minimum–maximum | 1.00–718.00 |
| ACS patients with coronary revascularization | 568 (14.12) |
| Recent medication history | |
| Anti-anginal agents | 2,435 (60.54) |
| Anticoagulants | 14 (0.35) |
| Antidiabetic drugs | 985 (24.49) |
| Antihypertensive agents | 304 (7.56) |
| Antiplatelet agents | 2,824 (70.21) |
| Colestimide | 100 (2.49) |
| EPA | 390 (9.70) |
| Fibrates | 164 (4.08) |
Unless indicated otherwise, data are given as n (%). ACS, acute coronary syndrome; AMI, acute myocardial infarction; CKD, chronic kidney disease; EPA, ethyl icosapentate; FH, familial hypercholesterolemia; IQR, interquartile range; LDL, low-density lipoprotein; PAD, peripheral artery disease; PCI, percutaneous coronary intervention.
The most common concomitant ASCVD was ACS (1,173 [29.16%]; specifically with acute myocardial infarction [619; 16.91%] and unstable angina [561; 13.95%]). There were 402 (10.00%) and 283 (7.04%) patients with cerebral infarction and peripheral artery disease, respectively. Chronic comorbid diseases identified included hypertension (2,504; 62.26%), heart failure (1,750; 43.51%), diabetes (1,199; 29.81%), and chronic kidney disease (297; 7.38%). In the cohort, 940 (23.37%) patients had a baseline medical history of FH. Baseline coronary revascularization was relatively frequent at 28.92% (n=1,163). In addition, 850 (21.13%) patients had a history of a prior ACS event within a 2-year look-back period. In this patient population, the mean time to the last event was 168.07 days and most patients had undergone coronary revascularization (568; 66.82%). As indicated in Supplementary Table 1, 2,575 (64.02%) patients had no ASCVD events diagnosed within the past 6 months. Approximately 36% of patients had at least 1 ASCVD event, with the most common being an ACS event (793; 19.72%). The most common comorbid disease was hypertension alone (1,432; 35.6%), followed by no comorbidities (1,240; 30.83%), and hypertension+diabetes (815; 20.26%).
LDL-C data were available for 6% (227/4,022) of patients. In the subsample with laboratory data, the mean LDL-C value was 132.37 mg/dL with a median value of 120 mg/dL (Supplementary Table 2). Among the 227 patients with available LDL-C results, the most common LDL-C range was relatively high at ≥100–180 mg/dL (115; 50.66%) and the mean concentration of non-high-density lipoprotein cholesterol was 156.69 mg/dL. Refers to most frequent category of HbA1c and filtration was 5.6–6.4% in 115 patients and the most common estimated glomerular filtration rate range was between 60 and 89 mL/min/1.73 m2 (Supplementary Table 2).
Evolocumab prescription patterns per study year are presented in Table 2. In terms of the size of medical institutions, large hospitals (≥200 beds) accounted for 88.59% of the total number of prescriptions and most patients received their initial evolocumab prescription in the outpatient rather than inpatient setting (3,170 [78.82%] vs. 852 [21.18%], respectively; Table 2). Most patients (2,759; 68.80%) were prescribed a dose of 140 mg evolocumab, and the most common mode of administration was the pen (58.80%), followed by the AMD (31.40%), and syringe (9.80%; Table 2).
Evolocumab Prescription Patterns (n=4,022)
| Year of evolocumab initiation | |
| 2016 | 202 (5.02) |
| 2017 | 531 (13.20) |
| 2018 | 774 (19.24) |
| 2019 | 624 (15.51) |
| 2020 | 1,281 (31.85) |
| 2021 | 610 (15.17) |
| Medical institution | |
| Large hospital (≥200 beds) | 3,563 (88.59) |
| Medium hospital (<200 beds) | 459 (11.41) |
| Clinic (<20 beds) | 0 (0.00) |
| Initial prescription setting | |
| Inpatient | 852 (21.18) |
| Outpatient | 3,170 (78.82) |
| Evolocumab prescription | |
| Dose | |
| 140 mg | 2,759 (68.60) |
| 420 mg | 1,263 (31.40) |
| Mode of administration | |
| Auto mini-doser | 1,263 (31.40) |
| Pen | 2,365 (58.80) |
| Syringe | 394 (9.80) |
Data show the number of patients in each group, with percentages in parentheses.
Utilization Patterns of Lipid-Lowering Regimens
Statin+ezetimibe, including statin/ezetimibe combination pills, was the most common (1,007; 25.04%) lipid-lowering regimen before evolocumab initiation, followed by no drug use (898; 22.33%; Table 3). Of the lipid-lowering regimens administered concomitant with evolocumab, statin+ezetimibe was the most common (1,281; 31.85%), followed by no concomitant treatment (1,910; 29.59%) and moderate intensity statin alone (631; 15.69%).
Recent Medication History: Lipid-Lowering Regimens (n=4,022)
| Lipid-lowering regimens before evolocumab initiationA | |
| No drug use | 898 (22.33) |
| Ezetimibe | 648 (16.11) |
| Alirocumab | 183 (4.55) |
| Ezetimibe+alirocumab | 79 (1.96) |
| Low-intensity statin | 97 (2.41) |
| Moderate-intensity statin | 449 (11.16) |
| High-intensity statin | 59 (1.47) |
| Statin+ezetimibeB | 1,007 (25.04) |
| Low-intensity statin | 78 (1.94) |
| Moderate-intensity statin | 584 (14.52) |
| High-intensity statin | 345 (8.58) |
| Statin+alirocumab | 143 (3.56) |
| Statin+ezetimibe+alirocumab | 166 (4.13) |
| Lipid-lowering regimens concomitant with evolocumab | |
| No concomitant treatment (i.e., evolocumab only) | 1,190 (29.59) |
| Ezetimibe | 601 (14.94) |
| Low-intensity statin | 199 (4.95) |
| Moderate-intensity statin | 631 (15.69) |
| High-intensity statin | 120 (2.98) |
| Statin+ezetimibe | 1,281 (31.85) |
| Low-intensity statin | 103 (2.56) |
| Moderate-intensity statin | 515 (12.80) |
| High-intensity statin | 663 (16.48) |
| Evolocumab treatment duration (days) | |
| Mean (±SD) | 420.26±463.54 |
| Median [IQR] | 260 [57.00–575.00] |
| Minimum–maximum | 1.00–2,773.00 |
| No. patients reinitiating evolocumab after discontinuationC | 509 (12.66) |
Unless indicated otherwise, data are given as n (%). ADuring the 6-month baseline period. BOnly statin+ezetimibe regimens include statin/ezetimibe combination pills. CDiscontinuation is defined as failure to have another evolocumab medication dispensed within 60 days after exhaustion of the days’ supply of the previous prescription dispensed.
Figure 2 shows changes in treatment from before (i.e., within 6 months) evolocumab initiation and on index date. Comparing the 2 time periods reveals that the proportion of patients with no additional lipid-lowering regimen increased from 24% to 29% after starting evolocumab. In some patients, statin and/or ezetimibe treatment seems to end treatment with the addition of evolocumab (i.e., on the index date). Because alirocumab is another PCSK9i, it was discontinued in all patients previously taking it when evolocumab treatment was initiated (i.e., the index date) without the addition of other lipid-lowering regimens. The proportion of patients treated with statin+ezetimibe increased from one-quarter to approximately one-third, due primarily to patients discontinuing alirocumab.
Changes in treatment from before evolocumab initiation to the index date.
Treatment Duration and Discontinuation/Reinitiation of Evolocumab
Figure 3 shows the duration of evolocumab treatment. For all patients, the mean and median duration of evolocumab treatment was 420.26 and 260.00 days, respectively. Of note, evolocumab was reinitiated after discontinuation in 509 (12.66%) patients. The probability of discontinuation in patients continuing on evolocumab beyond 575 days was <25%; around this time there was a considerable decline in the number of patients continuing on evolocumab.
Evolocumab treatment duration. CI, confidence interval.
FH Subgroup Analysis
In this study cohort, 940 (30.49%) patients were diagnosed with FH (Table 4). More patients with than without FH were aged <65 years (516 [54.89%] vs. 1,336 [43.35%], respectively) and more patients in the FH than non-FH group were female (360 [38.30%] vs. 928 [30.11%], respectively). Almost all FH patients received their initial evolocumab prescription in the outpatient setting (855; 90.96%), compared with only 78.49% (2,419) of patients without FH.
Patient Characteristics According to Familial Hypercholesterolemia Status
| Diagnosis of FH (n=940) |
No diagnosis of FH (n=3,082) |
|
|---|---|---|
| Age at evolocumab initiation (years) | 61.05±13.31 | 64.83±12.71 |
| Sex | ||
| Female | 360 (38.30) | 928 (30.11) |
| Male | 580 (61.70) | 2,154 (69.89) |
| Evolocumab prescription | ||
| Dose | ||
| 140 mg | 720 (76.60) | 2,039 (66.16) |
| 420 mg | 220 (23.40) | 1,043 (33.84) |
| Mode of administration | ||
| Auto mini-doser | 220 (23.40) | 1,043 (33.84) |
| Pen | 571 (60.74) | 1,794 (58.21) |
| Syringe | 149 (15.85) | 245 (7.95) |
| Initial prescription setting | ||
| Inpatient | 85 (9.04) | 767 (24.89) |
| Outpatient | 855 (90.96) | 2,315 (75.11) |
| Treatment duration of evolocumab (days) | ||
| Mean (±SD) | 564.14±529.65 | 376.38±432.08 |
| Median [IQR] | 484 [134.00–729.00] | 204 [57.00–552.00] |
| Minimum–maximum | 15.00–2,773.00 | 1.00–2,626.00 |
| No. patients reinitiating evolocumab after discontinuation | 139 (14.79) | 370 (12.01) |
| Kaplan-Meier estimation of discontinuation of first evolocumab (days) | ||
| Median [95% CI] | 484 [437–505] | 204 [183–225] |
Unless indicated otherwise, data are given as n (%). CI, confidence interval; FH, familial hypercholesterolemia; IQR, interquartile range.
The mean treatment duration for patients with and without a diagnosis of FH was 564.14±529.65 and 376.38±432.08 days, respectively. The clinical profiles of the 2 subgroups were similar, including the proportion of patients who reinitiated evolocumab after discontinuation (14.79% vs. 12.01% in the FH and non-FH groups, respectively). The KM estimation revealed that the medium time to discontinuation of a patient›s first continuous treatment in the FH group was 484.00 days (95% Cl 437.00–505.00 days), which was more than double that in the non-FH group (204.00 days; 95% Cl 183.00–225.00). The results of all other subgroup analyses are presented in Supplementary Figures 1–8 and Supplementary Tables 3–6.
In Japan, evolocumab is commonly used for patients with ASCVD or FH, especially those with chronic comorbid conditions such as hypertension or diabetes. Patients who start evolocumab tend to have relatively high LDL-C concentrations. Intensive statin therapy is not widely used as a concomitant lipid-lowering regimen in Japan, with moderate/mild statins dosages and/or ezetimibe more often used. Evolocumab is mostly initiated in the outpatient setting at large hospitals. Treatment adherence to evolocumab is good, especially in patients with FH. These findings suggest that evolocumab has been widely, and consistently, used in Japan since its introduction; however, gaps remain in optimizing its use for better lipid management in Japanese patients (see below).
According to Japanese lipid guideline, the LDL-C target in patients with a history of ASCVD is 100 mg/dL, whereas a more stringent target of 70 mg/dL is recommended for patients with high-risk conditions like FH, ACS, atherothrombotic cerebral infarction, and diabetes.5 In the present study, we observed that physicians prescribed evolocumab at a mean LDL-C concentration approaching 130 mg/dL. Thus, there may be a considerable number of individuals with LDL-C concentrations in the range 70–120 mg/dL and high-risk conditions who remain untreated. Based on recently published real-world data, among Japanese patients at high risk of atherosclerosis, the LDL-C concentration in most patients was between 70 and 120 mg/dL after intensive statin treatment.18 Our results underscore the existing gap in the use of PCSK9i in this population, emphasizing that many individuals have not received adequate treatment to achieve the guideline-recommended LDL-C targets.
In Western countries, high-intensity statins are used by up to 22% of primary prevention patients, with achievement of LDL-C goals more likely with combination treatment.19 We found that the frequency of high-intensity statin usage was considerably lower in Japan (~8% of those who use evolocumab). This may be related to the safety concerns regarding the use of intensive statins in the Japanese population.20 Furthermore, we found that one-third of patients had no concomitant treatment at the time of evolocumab initiation and a discontinuation time of <5 years. This observation may be attributed to various factors, including statin intolerance, physicians adjusting or discontinuing statins due to concerns about low LDL-C concentrations, and limitations in data types collected by the MDV database. Based on these patterns of concomitant treatment and evolocumab discontinuation, it appears that current practices sometimes deviate from the guidelines.5 Further information on combination therapy and proper drug usage should be disseminated.
Emerging evidence on non-statin lipid-lowering therapy from within and outside of Japan, including from FOURIER and A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Effect of Alirocumab (SAR236553/REGN727) on the Occurrence of Cardiovascular Events in Patients Who Have Recently Experienced an Acute Coronary Syndrome (ODESSEY OUTCOMES) trials,7 have repeatedly shown “the lower the better” to be a cornerstones of ASCVD secondary prevention. International guidelines also adopt stricter LDL-C targets for ASCVD secondary prevention. In the recent American College of Cardiology expert consensus decision pathway, ASCVD patients were stratified into very high risk and non-very high risk groups.12 For very high risk ASCVD, the LDL-C threshold was set to 55 mg/dL with the recommendation of adding non-statin therapies.12 Corresponding guidelines in Japan were updated in 2022.5 Although the guidelines propose stricter LDL-C targets for FH and diabetes than for other conditions, the target is set at <70 mg/dL LDL-C, and no further risk stratification is provided.5 Our study demonstrates that FH, hypertension, heart failure, and diabetes may be prominent comorbidities for physicians to consider when prescribing evolocumab. Our findings suggest that these comorbidities could be regarded as risk stratification criteria in future Japanese lipid guidelines. Further epidemiological studies could explore whether patients with these comorbidities are more prone to recurrent cardiovascular events.
Study LimitationsThis study is a secondary analysis of administrative health data. These data items are primarily based on hospital data (i.e., few clinics, where the clinical focus is primary prevention in Japan) and long-term follow-up is limited. For these reasons, the long-term utilization of evolocumab may have been underestimated. In addition, few patients in this dataset had LDL-C laboratory data, so further assessment of LDL-C and the effectiveness of evolocumab was not possible.
Only data for patients who receive treatment at medical institutions is shared with the MDV database and could be included in our analyses. Patients treated at other medical institutions outside the scope of the database are not be captured in this database. However, using a commercially available patient database to assess characteristics, in addition to using the largest hospital-based database in Japan, should expand the range of the population represented by our study.
This study provides valuable insights into the real-world clinical profiles of Japanese patients treated with evolocumab. The high prevalence of FH and ASCVD events with comorbidities emphasizes the utility of evolocumab not only in reducing LDL-C levels, but also in protecting against cardiovascular events. However, the relatively high baseline LDL-C concentrations indicate that there is still a large untreated patient population with moderately high baseline LDL-C. Continued efforts towards medical education regarding clinical guidelines and proper usage will better support evolocumab access in the Japanese population.
This work was supported solely by Amgen K.K., which paid service fees to Syneos Health and funded this study, participated in the study design, research, analysis, data collection, interpretation of data, reviewing, and approval of the publication.
F.S., A.Y.W., K.M., T.T., N.O. are employees of Amgen K.K. R.M. and Z.F. are employees of Syneos Health. T.O. has received lecture fees from Kowa Company Ltd. and Bayer, as well as Donations Scholarship funds granted by Suntory Global Innovation Center.
This study was approved by the Public Health Research Foundation (PHRF; Reference no. 22E0005).
The data that support the findings of this study are from MDV Co., Ltd. used under license; therefore, restrictions apply and the data are not publicly available. For inquiries about access to the dataset used in this study, please contact MDV (https://en.mdv.co.jp/).
Please find supplementary file(s);
https://doi.org/10.1253/circj.CJ-23-0814
