Abstract
Background: The prognosis for survivors of acute coronary syndrome (ACS) remains substantially worse compared with the general population. In Japan, regional clinical alliance paths (RCAPs) have been promoted to support the secondary prevention of ACS within community settings. However, the implementation of RCAPs is currently low, and their clinical efficacy has not been established. This study evaluated the impact of RCAP implementation on secondary prevention outcomes in ACS patients.
Methods and Results: Of 405 patients admitted to Tottori University Hospital for ACS between May 2020 and April 2023, 136 who underwent primary percutaneous coronary intervention (PCI) and received follow-up care at primary care clinics were included in the study. Sixty-five (47.8%) patients received care under an RCAP, whereas 71 received standard care. RCAP implementation was associated with a higher proportion of patients achieving low-density lipoprotein cholesterol (LDL-C) levels below 70 mg/dL and with greater reductions in LDL-C levels overall. Propensity score-weighted analysis confirmed that the RCAP group achieved significantly better LDL-C control after adjustment for baseline characteristics using inverse probability weighting.
Conclusions: RCAP implementation improved the rate of LDL-C target achievement and the degree of LDL-C reduction in post-ACS patients receiving follow-up care from family physicians. RCAP implementation is an effective strategy for the secondary prevention of ACS, particularly by enhancing adherence to established pharmacological therapies.
Primary percutaneous coronary intervention (PCI) has greatly reduced mortality in patients with ST-segment elevation myocardial infarction (STEMI) and is now the standard of care in most Japanese institutions.1 Although the prognosis for survivors of acute coronary syndrome (ACS) has improved, it remains substantially worse compared with the general population.2 Current guidelines for managing ACS emphasize strict and continuous lipid-lowering therapy for secondary prevention.3 However, it is not feasible to follow-up all patients who undergo primary PCI for ACS at facilities performing PCI because these facilities often centralize services or divide responsibilities among hospitals. Many patients transition to primary care clinics, including those without cardiology specialists, for long-term treatment.
The Japanese guidelines on regional clinical alliances highlight 2 key issues for effective secondary prevention of ACS: educating patients and their families on the importance and methods of secondary prevention, and encouraging them to participate in an appropriate care system.3 In 2007, the Medical Service Law in Japan was revised to promote the use of regional clinical alliance paths (RCAPs). This initiative aimed to establish a clear division of roles between acute- and chronic-phase medical institutions and to ensure a seamless transition of medical care from the acute phase to the chronic phase. ACS was identified as one of the target conditions for RCAP. In response to that policy, efforts to implement RCAP for acute myocardial infarction began in various regions of Japan. However, the implementation of RCAP programs currently is low, and their clinical efficacy has not been established.4
Suboptimal handovers at hospital discharge generally lead to increased rehospitalizations and decreased quality of healthcare. Some interventions by medical staff have shown positive effects on patient care.5 However, there is a lack of evidence that effective communication and collaboration, including the use of RCAP, has improved outcomes or enhanced the quality of care in the secondary prevention of ACS.
The Tottori Seibu Medical Association ACS Community Collaboration Path, an RCAP, was developed to provide patients with safe, high-quality medical care and to support the secondary prevention of ACS. This initiative aims to enhance patient awareness of their condition while facilitating the sharing of treatment plans and goals between primary PCI facilities and primary care clinics. The RCAP was introduced in the region in 2014 and revised to its current form in 2020; the current form emphasizes intensive lipid-lowering therapy and a shortened duration of dual antiplatelet therapy after PCI. The rate of RCAP implementation has increased steadily since its introduction. The present study evaluated the impact of RCAP implementation on secondary prevention outcomes in ACS patients.
Methods
Study Population and Design
The present retrospective study was approved by the Tottori University Institutional Review Board and was conducted in accordance with the Declaration of Helsinki. Information about the study was made publicly available in compliance with the guiding principles for epidemiological studies established by the Japanese Ministry of Health, Labour, and Welfare. Data collection and analysis were conducted without acquiring written informed consent from individual patients, as permitted under these guidelines.
We analyzed 405 patients admitted to Tottori University Hospital for ACS between May 2020 and April 2023. Patients who underwent primary PCI and received follow-up care at primary care clinics were included in the study. The cohort was divided into 2 groups based on whether patient care involved the RCAP (Figure 1). Coronary risk factor control and chronic-phase prognosis were compared between the 2 groups.
Clinical Follow-up and RCAP Implementation by Tottori Seibu Medical Association
Daily clinical care was provided by primary care clinics; one-time outpatient consultations were planned at the primary PCI facilities. All patients were scheduled for at least 2 follow-up visits at the primary PCI facility within 1–12 months after primary PCI, depending on their clinical condition. Blood pressure, low-density lipoprotein cholesterol (LDL-C) levels, HbA1c levels, smoking rates, symptoms, and adverse events, including bleeding, death, and unplanned hospitalization during outpatient consultation, were compared between the groups.
The RCAP was indicated for ACS patients who had undergone coronary intervention, were expected to have a standard recovery course without severe complications, had completed coronary revascularization, and were receiving follow-up care at primary care clinics. The decision to implement the RCAP was made by the physician at the primary PCI facility. The RCAP developed by the Tottori Seibu Medical Association consists of 2 main components: patient education (Figure 2) and cooperation between primary PCI facilities and primary care clinics (Figure 3). A cooperation sheet was used to share information at each visit. The cooperation sheet includes primary PCI and targets of coronary risk factors. The patient’s data is written interactively between the primary care clinic and the PCI facility regarding the control status of coronary risk factors and specific symptoms or signs to watch during follow-up. Family physicians made clinical decisions based on this information, focusing on antiplatelet therapy management and LDL-C control.
Data Collection
Patient characteristics recorded were sex, age, hypertension, dyslipidemia, initial LDL-C level, diabetes, initial HbA1c level, smoking status, atrial fibrillation, chronic kidney disease status, dialysis status, body weight, and diagnosis. Hypertension was defined as systolic blood pressure >140 mmHg, diastolic blood pressure >90 mmHg, or the use of antihypertensive medication. Dyslipidemia was defined as LDL-C ≥140 mg/dL, high-density lipoprotein cholesterol <40 mg/dL, triglycerides ≥150 mg/dL, non-high-density lipoprotein cholesterol >170 mg/dL, or treatment for dyslipidemia. Diabetes was defined as fasting plasma glucose ≥126 mg/dL, random plasma glucose ≥200 mg/dL, 2-h plasma glucose ≥200 mg/dL during a 75-g oral glucose tolerance test, HbA1c >6.5%, or treatment for diabetes. Chronic kidney disease was defined as the presence of proteinuria, serum creatinine ≥1.3 mg/dL, or an estimated glomerular filtration rate ≤60 mL/min/1.73 m2.6
Primary PCI was performed according to standard protocols in Japan.1 The number of diseased vessels was determined during initial coronary angiography, and residual stenosis was evaluated at discharge. Significant stenosis was defined as >70% diameter narrowing by visual estimation in a vessel with a diameter >2.5 mm. Initial left ventricular ejection fraction measured by echocardiography and medications prescribed at discharge were also analyzed.
Outcomes were evaluated in terms of coronary risk factor control and prognosis at 1 year. The achievement rate of target LDL-C <70 mg/dL for the secondary prevention of ACS,3 LDL-C reduction, and the overall decrease in LDL-C were also assessed. LDL-C decrease was calculated as (initial LDL-C–chronic LDL-C); LDL-C reduction was defined as (LDL-C decrease/initial LDL-C). The prescription rates of lipid-lowering therapies and the percentage of clinics specializing in cardiovascular care were also examined. Adverse events were defined as target vessel revascularization, bleeding that warranted hospitalization or transfusion, unexpected hospitalizations, all-cause mortality, and any events that constituted a composite of these adverse events.
Statistical Analysis
Continuous variables are reported as the median with interquartile range; categorical variables are presented as percentages. The Mann-Whitney U test was used to compare continuous variables, whereas Pearson’s Chi-squared test was used to compare categorical variables. To minimize bias and evaluate the effect of RCAP implementation on event occurrence and achievement of LDL-C <70 mg/dL, we adjusted for background factors using inverse probability weighting. These factors included sex, age, dyslipidemia status, initial LDL-C level, diagnosis (STEMI, non-STEMI [NSTEMI], unstable angina), left ventricular ejection fraction, and the use of ezetimibe. P<0.05 was considered statistically significant. All analyses were conducted using R version 4.3.1 (R Foundation for Statistical Computing, Vienna, Austria) and EZR (Saitama Medical Center, Jichi Medical University, Saitama, Japan), a graphical user interface for R (Version 2.13.0; R Foundation for Statistical Computing).7
Results
Patient Characteristics
In total, 247 ACS patients underwent primary PCI at Tottori University Hospital and were discharged home. Of these, 108 patients received follow-up care at a general hospital, whereas 139 were followed-up by family physicians. Three of the 139 patients were excluded from the analysis: 1 dropped out and 2 planned to miss medical visits because of advanced age and long travel distances to the clinic. Ultimately, 136 patients were included in the analysis: 65 in the RCAP group (47.8%) and 71 in the control group, without RCAP implementation. Most patients (71.3%) received follow-up care at clinics without cardiology specialists. Although the RCAP group showed a trend towards fewer male patients, higher initial LDL-C levels, a greater proportion of patients with diabetes, and a higher rate of ezetimibe use, there were no statistically significant differences in baseline characteristics between the 2 groups (Table 1).
Table 1.
Patient Characteristics
| |
RCAP group
(n=65) |
Control group
(n=71) |
P value |
| Male sex |
51 (78.5) |
62 (87.3) |
0.18 |
| Age (years) |
72.0 [61.0–80.0] |
69.0 [61.0–76.5] |
0.16 |
| Hypertension |
48 (73.8) |
50 (70.4) |
0.71 |
| Dyslipidemia |
39 (60.0) |
39 (54.9) |
0.61 |
| LDL-C (mg/dL) |
110.0 [87.3–136.8] |
103.0 [89.0–127.0] |
0.42 |
| Total cholesterol (mg/dL) |
175.0 [115.0–291.0] |
174.5 [101.0–701.0] |
0.84 |
| HDL-C (mg/dL) |
47.5 [28.0–79.0] |
47 [20.0–92.0] |
0.82 |
| TG (mg/dL) |
100.0 [24.0–303.0] |
95.0 [18.0–780.0] |
0.54 |
| Diabetes |
25 (38.5) |
21 (29.6) |
0.28 |
| Glucose (mg/dL) |
115.5 [74.0–354.0] |
118.0 [84.0–320.0] |
0.40 |
| HbA1c (%) |
6.1 [5.7–6.7] |
6.0 [5.7–6.6] |
0.66 |
| Smoking |
17 (26.2) |
21 (29.6) |
0.71 |
| Atrial fibrillation |
8 (12.3) |
10 (14.1) |
0.81 |
| Chronic kidney disease |
20 (30.8) |
26 (36.6) |
0.59 |
| Dialysis |
2 (3.1) |
3 (4.2) |
1.0 |
| Body weight (kg) |
61.0 [53.2–70.2] |
62.3 [55.5–69.3] |
0.90 |
| Diagnosis |
| STEMI |
43 (66.2) |
45 (63.4) |
|
| NSTEMI |
16 (24.6) |
16 (22.5) |
|
| UAP |
6 (9.2) |
10 (14.1) |
0.82 |
| Lesion location |
| LMT |
2 (3.3) |
3 (4.5) |
|
| LAD |
33 (55.0) |
30 (45.5) |
|
| LCX |
7 (11.7) |
7 (10.6) |
|
| RCA |
18 (30.0) |
26 (39.4) |
0.69 |
| No. diseased vessels |
1.0 [1.0–2.0] |
1.0 [1.0–2.0] |
0.10 |
| Residual stenosis |
0 [0–1.0] |
0 [0–1.0] |
0.13 |
| LVEF (%) |
52.5 [45.0–60.0] |
50.0 [40.0–59.8] |
0.14 |
| Medication at discharge |
| Aspirin |
56 (86.2) |
61 (85.9) |
1.0 |
| P2Y12 inhibitor |
63 (96.9) |
63 (88.7) |
0.10 |
| Anticoagulation |
11 (16.9) |
10 (14.1) |
0.81 |
| Statin |
65 (100) |
68 (95.8) |
0.25 |
| Ezetimibe |
19 (29.2) |
13 (18.3) |
0.16 |
| Fibrate |
0 (0.0) |
2 (2.8) |
0.50 |
| PCSK9i |
0 |
0 |
|
| n-3 PUFA |
1 (1.5) |
3 (4.2) |
0.62 |
| β-blocker |
52 (80.0) |
59 (83.1) |
0.66 |
| ACE/ARB |
45 (69.2) |
47 (66.2) |
0.72 |
| ARNI |
5 (7.7) |
2 (2.8) |
0.26 |
| MRA |
7 (10.8) |
13 (18.3) |
0.24 |
| SGLT2i |
10 (15.4) |
7 (9.9) |
0.45 |
Unless indicated otherwise, data are given as the median [interquartile range] or n (%). ACE, angiotensin-converting enzyme inhibitor; ARB, angiotensin II receptor blocker; HDL-C, high-density lipoprotein cholesterol; LAD, left anterior descending coronary artery; LCX, left circumflex coronary artery; LDL-C, low-density lipoprotein cholesterol; LMT, left main trunk; LVEF, left ventricular ejection fraction; MRA, mineralocorticoid receptor antagonist; n-3 PUFA, n-3 polyunsaturated fatty acids; NSTEMI, non-ST-elevation myocardial infarction; PCSK9i, proprotein convertase subtilisin/kexin type 9 inhibitor; RCA, right coronary artery; RCAP, regional clinical alliance path; SGLT2i, sodium-glucose cotransporter 2 inhibitor; STEMI, ST-elevation myocardial infarction; TG, triglyceride; UAP, unstable angina.
Outcomes
Clinical follow-up outcomes are summarized in Table 2. The median follow-up period was 366 days; there were no significant differences in adverse event rates between the 2 groups. LDL-C control tended to be better in the RCAP group, which achieved a significantly higher rate of LDL-C <70 mg/dL. In addition, LDL-C reduction from baseline was significantly greater in the RCAP group. Statin prescription rates were slightly lower during the chronic phase than at discharge in both groups.
Table 2.
Outcomes and Medication During the Chronic Phase
| |
RCAP group
(n=65) |
Control group
(n=71) |
P value |
| Target vessel revascularization |
3 (4.6) |
3 (4.2) |
1.0 |
| Bleeding |
0 |
3 (4.2) |
0.25 |
| Unexpected hospitalization |
7 (10.8) |
12 (16.9) |
0.33 |
| All cause death |
0 |
1 (1.1) |
1.0 |
| Any event |
7 (10.8) |
13 (18.3) |
0.24 |
| Smoking |
4 (6.3) |
6 (8.7) |
0.75 |
| Aspirin |
34 (54.0) |
42 (60.9) |
0.48 |
| P2Y12 inhibitor |
29 (46.0) |
31 (44.9) |
1.0 |
| Anti-coagulation |
8 (12.7) |
10 (14.3) |
0.81 |
| Statin |
62 (98.4) |
64 (92.8) |
0.21 |
| Statin dose up at follow up |
3 (4.8) |
4 (5.8) |
1.0 |
| Ezetimibe |
25 (39.7) |
18 (25.7) |
0.10 |
| Fibrate |
1 (1.6) |
3 (4.3) |
0.62 |
| PCSK9i |
0 |
0 |
|
| n-3 PUFA |
2 (3.1) |
3 (4.3) |
1.0 |
| β-blocker |
49 (77.6) |
55 (78.6) |
0.84 |
| ACE/ARB |
40 (62.5) |
46 (62.9) |
1.0 |
| ARNI |
5 (7.8) |
0 (0) |
0.02 |
| MRA |
9 (14.1) |
11 (15.7) |
0.24 |
| SGLT2i |
16 (25.0) |
8 (11.4) |
0.05 |
| Blood pressure (mmHg) |
125 [85.0–135.8] |
122 [86.0–138.0] |
0.82 |
| LDL-C (mg/dL) |
64.0 [50.5–75.5] |
71.5 [55.8–83.0] |
0.15 |
| LDL-C <70 mg/dL |
38 (65.5) |
29 (45.3) |
0.03 |
| LDL-C decrease (mg/dL) |
52.5 [45.0–60.0] |
36.0 [19.0–55.3] |
0.03 |
| LDL-C reduction |
45.0 [30.4–54.2] |
36.6 [22.3–49.3] |
0.05 |
| Total cholesterol (mg/dL) |
140.0 [108.0–298.0] |
149.0 [68.0–212.0] |
0.47 |
| HDL-C (mg/dL) |
51.0 [28.0–121.0] |
50.5 [24.0–89.0] |
0.49 |
| TG (mg/dL) |
128.0 [42.0–558.0] |
106.0 [48.0–327.0] |
0.68 |
| Glucose (mg/dL) |
104.0 [73.0–310.0] |
116.5 [78.0–301.0] |
0.53 |
| HbA1c (%) |
6.2 [5.9–6.9] |
6.2 [5.7–6.7] |
0.50 |
| Systolic blood pressure (mmHg) |
126.00 [85.00–180.00] |
126.00 [86.00–180.00] |
0.86 |
| Body weight (kg) |
63.1 [56.4–71.6] |
63.3 [56.0–71.9] |
0.90 |
| Cardiovascular clinics |
20 (30.8) |
19 (26.8) |
0.71 |
| Outpatient education by nurse |
32 (58.2) |
32 (51.6) |
0.58 |
| Outpatient cardiac rehabilitation |
2 (3.6) |
3 (4.8) |
1.0 |
| Follow-up period (days) |
366.0 [347.0–380.0] |
366.0 [351.5–381.5] |
0.71 |
Unless indicated otherwise, data are given as the median [interquartile range] or n (%). Abbreviations as in Table 1.
Propensity Score Weighting Analysis
Background adjustment using inverse probability weighting for any event and LDL-C <70 mg/dL resulted in wellbalanced factors; standard deviations for all variables were <0.1 after adjustment (Supplementary Table). In the propensity score-weighted analysis (Table 3), the RCAP group demonstrated a significantly higher achievement rate of LDL-C <70 mg/dL after background adjustment. However, there was no significant difference in the occurrence of adverse events between the 2 groups.
Table 3.
Propensity Score Weighting Analysis for the Regional Clinical Alliance Path
| |
Risk ratio |
95% Confidence
interval |
P value |
| Any event |
0.56 |
0.23–1.32 |
0.18 |
| LDL-C <70 mg/dL |
1.54 |
1.08–2.19 |
0.02 |
LDL-C, low-density lipoprotein cholesterol.
Discussion
More than half the patients who underwent primary PCI for ACS were followed up by family physicians, mainly in clinics without cardiology specialists. The implementation of RCAP led to higher rates of achieving LDL-C <70 mg/dL and greater reductions in LDL-C levels among these patients. Even in the propensity score-weighted analysis including the use of ezetimibe, implementation of RCAP resulted in a significantly higher achievement rate of LDL-C <70 mg/dL. RCAP consisting of patient education and collaboration with the primary care clinic was shown to be useful in achieving LDL-C targets.
Patients with ACS exhibit a high risk of recurrent cardiovascular events; studies have demonstrated that the reduction in event risk is proportional to the absolute reduction in LDL-C levels.8 The 2021 European Society of Cardiology guidelines recommend an initial LDL-C goal of <70 mg/dL (1.8 mmol/L) in patients with established atherosclerotic cardiovascular disease, followed by a more stringent target of <55 mg/dL (<1.4 mmol/L).9 Although updated Japanese guidelines set stricter LDL-C targets (<70 mg/dL),3 the actual rate of achieving these targets was only 31.8% in a recent ACS cohort in Japan.10 Statin withdrawal has also been associated with higher mortality rates.11 Sharing strategies for secondary prevention of ACS with family physicians and educating patients are essential steps in improving outcomes. The findings of the present study suggest that RCAP implementation offers an effective, systematic approach to addressing these challenges.
Although the present study did not directly evaluate the effect of RCAP implementation on patient education, patient education may contribute to the achievement of treatment goals. A questionnaire survey of patients with diabetes and cardiovascular disease reported that fewer patients (2.4%) knew the correct treatment target for LDL-C than for HbA1c.12 In addition, there has been a report about association of knowledge of LDL-C goals and LDL-C target achievement.13
There were no significant differences in other risk factors, such control of blood pressure, HbA1c, and smoking cessation. It is possible that smoking cessation, blood pressure control, and HbA1c targets were familiar to patients and were relatively easy to achieve. HbA1c <7.0% was achieved by over 78% of patients in both groups. Because HbA1c measurement in non-diabetic patients is not recommended in Japanese insurance, there were many missing data during the follow-up period and it was possible that the achievement rate may be even better.
In Japan, the Medical Service Law was revised in 2007 to promote RCAP implementation, with the aim of facilitating a seamless transition from acute to chronic care. However, its adoption has remained limited. Arakawa et al. reported that the rate of RCAP implementation after acute myocardial infarction was very low (10%); the primary reasons for non-implementation were “Do not feel necessity” and “Increased duties for doctors,” as well as underdeveloped communication methods.4 In the present study, the rate of RCAP implementation was 47.8%. Despite this relatively high rate, it is unlikely that the RCAP has been fully integrated into routine practice. Furthermore, the shortened length of hospital stays for acute care and the busy schedules of physicians in recent years may have further discouraged RCAP implementation. To enhance RCAP development and improve secondary prevention of ACS, it is important to lower barriers to implementation, involve more medical staff from both hospitals and community health systems, and pursue medical standardization through digital transformation.14 Sharing treatment goals and pathways with patients and community care providers is an important aspect of RCAP and, with that in mind, automating the entry and sharing process may be effective. Communication via a complicated status sheet may be ineffective given physicians’ workload, and a protocol sheet may be a good idea, at least for LDL-C control.15
It is also important to continue to ensure the quality of the RCAP in order for its effectiveness to be extrapolated to any region. Although RCAPs are still in operation in different regions, a recent Japanese survey reported that LDL-C targets are not defined as LDL-C <70 mg/dL in some clinical pathways in Japan.15 There were no prescriptions of proprotein convertase subtilisin/kexin type (PCSK) 9 inhibitors in this study. This may be because high-risk and difficult-to-control LDL-C patients who had an indication for PCSK9 inhibitors were treated in primary PCI facilities or other general hospitals. In fact, a survey on PCSK9 inhibitor prescription in Japan reported that the number of prescriptions at community clinics was low.16 However, considering that it is now reasonable to have intense lipid-lowering therapy with an LDL target of <55 mg/dL,17 our RCAP should be updated accordingly.
Study Limitations
First, this was a retrospective observational single-center study. It remains unclear whether similar effects would be seen in other healthcare systems. Second, RCAP implementation was left to the discretion of the attending physician, hindering complete equalization of patient backgrounds. Patients with better cognitive function and adherence may have been preferentially included in the RCAP group. The possibility of incomplete adjustment for other important background factors cannot be ruled out, which is a limitation of retrospective studies. Further investigation using prospective registries is warranted. As for the no significant differences found in this study with regarding to outcomes, further long-term follow-up is needed to investigate the impact of RCAP on outcomes. In addition, interactive communication of information within the RCAP did not always function effectively, depending on the physician involved. RCAP operations could be enhanced through greater participation from rural pharmacists and other healthcare professionals.
The frequency of outpatient cardiac rehabilitation in this study was extremely low, due to the fact that many eligible patients were followed up at their own institutions and the effects of the COVID-19 period. More intensive patient education can be expected by combining cardiac rehabilitation.
Conclusions
RCAP implementation increased the rate of achieving LDL-C targets and improved LDL-C reduction in post-ACS patients receiving follow-up care from family physicians. The RCAP may represent an effective strategy for the secondary prevention of ACS by enhancing adherence to guideline-directed medical therapy.
Acknowledgments
The authors sincerely thank the members of the Tottori Seibu Medical Association ACS Community Collaboration Path. The authors also thank Ryan Chastain-Gross, PhD, from Edanz (https://jp.edanz.com/ac) for editing a draft of this manuscript.
Sources of Funding
This study did not receive any specific funding.
Disclosures
K. Yamamoto is a member of Circulation Journal’s Editorial Team. The remaining authors have no conflicts of interest to disclose.
IRB Information
This study was approved by the Tottori University Institutional Review Board (Reference no. 2418).
Data Availability
The deidentified participant data will not be shared.
Supplementary Files
Please find supplementary file(s);
https://doi.org/10.1253/circj.CJ-25-0059
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