Clinical trial NCT06845410: Clinical Features, Current Treatment and Clinical Outcomes in Patients With INR-CAD: a Cohort Study
Official title: Clinical Features, Current Treatment and Clinical Outcomes in Patients With Inflammation-associated Non-rapidly-progressive Coronary Artery Disease (INR-CAD): a Cohort Study
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Coronary Artery Disease
Coronary Artery Disease Progression
Coronary Artery Stenosis
Coronary Artery Restenosis
Inflammation
Inflammatory Disease
Inflammation Vascular
Keywords: Coronary Artery Disease
Progression, Disease
Inflammation
Lead sponsor: Peking Union Medical College Hospital
Sponsor class: OTHER
First posted: 2025-02-25
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: All patients who have been admitted to the Department of Cardiology, Peking Union Medical College Hospital (PUMCH) since January 1, 2022 will be screened for study participation.

Brief summary: This is a cohort study to investigate the clinical features, current treatment and clinical outcomes in patients with inflammation-associated non-rapidly-progressive coronary artery disease (INR-CAD).

Detailed description: A special type of coronary artery disease (CAD) has been identified in our clinical practice. The patients have significantly different clinical features from those of typical atherosclerotic coronary artery disease (AS-CAD), including: 1) predominantly female; 2) early onset CAD; 3) lack of traditional atherosclerotic risk factors; 4) often with evidence of chronic inflammation; 5) responding poorly to intensified secondary prevention and optimized coronary revascularization (percutaneous coronary intervention \[PCI\] or coronary bypass graft \[CABG\]); 6) delayed disease progression on immunosuppressive therapy. This special type of CAD is named with inflammation-associated coronary artery disease (I-CAD). Currently, the pathogenesis as well as the optimal approach regarding the diagnosis and treatment of I-CAD remain unknown.

Based on the rate of disease progression and the urgency for clinical management, I-CAD is classified into two categories: 1) inflammation-associated rapidly-progressive coronary artery disease (IR-CAD), which is defined as I-CAD with progression of coronary de novo and/or restenotic lesions within 6 months or within 12 months (only for patients receiving immunosuppressive therapy within 24 months); 2) inflammation-associated non-rapidly-progressive coronary artery disease (INR-CAD), which is defined as I-CAD not fulfilling the criteria for IR-CAD.

It has been recognized in our clinical practice that INR-CAD is a highly heterogeneous group of diseases. Therefore, the present observational cohort study was designed to investigate the clinical features, current treatment and clinical outcomes in patients with INR-CAD.

All patients who have been admitted to the Department of Cardiology, Peking Union Medical College Hospital (PUMCH) since January 1, 2022 will be screened for study participation. Clinical diagnostic criteria and a clinical follow-up protocol have been specifically designed for INR-CAD in our center. Patients are clinically diagnosed as INR-CAD if they 1) have angiographic evidence of coronary lesions (de novo or restenotic); 2) have evidence of chronic inflammation (positive inflammatory markers or positive autoantibodies or established diagnosis of chronic inflammatory diseases or use of immunosuppressive therapy) within 24 months; 3) not meet the clinical diagnostic criteria for IR-CAD. Once the clinical diagnosis is established, INR-CAD patients will receive a 24-month clinical follow-up according to the clinical follow-up protocol for INR-CAD in PUMCH. Patients who have been clinically diagnosed as INR-CAD and received, or are receiving, or will receive the 24-month clinical follow-up will be enrolled in the present cohort study.

The primary efficacy endpoint is major adverse cardiovascular events (MACE). The secondary efficacy endpoints include the individual components of MACE, exercise capacity, angiographic metrics of coronary lesions, and inflammatory markers. The safety endpoints are major bleeding events and severe infection events.

For the endpoints which are categorical variables, e.g., MACE, the event rate for the first occurrence of each endpoint during the 24-month clinical follow-up will be calculated. Chi-square test or Fisher's exact test will be used to compare the event rate for each endpoint between patients with different diagnosis and/or those receiving different treatment, including patients 1) with vs. without established diagnosis of chronic inflammatory diseases; 2) receiving vs. not receiving immunosuppressive therapy; 3) receiving vs. not receiving coronary revascularization.

For the endpoints which are continuous variables, e.g., inflammatory markers, 1) paired t-test or paired rank sum test will be used to compare the level of each endpoint at the end of the 24-month clinical follow-up with that at baseline (the diagnosis of INR-CAD); 2) analysis of co-variance (ANCOVA) will be used to compare the level of each endpoint at the end of the 24-month clinical follow-up between patients with different diagnosis and/or those receiving different treatment, including patients ① with vs. without established diagnosis of chronic inflammatory diseases; ② receiving vs. not receiving immunosuppressive therapy; ③ receiving vs. not receiving coronary revascularization.

Eligibility criteria: Inclusion criteria

1. 18 years of age or older, male or female.
2. Negative results of urine or blood pregnancy test for females with childbearing potential (not post-menopausal or surgically sterile).
3. Meeting the clinical diagnostic criteria for INR-CAD, including: (1) Angiographic evidence of coronary lesions (≥ 50% diameter stenosis, de novo or restenotic); (2) Evidence of chronic inflammation within 24 months: (A) Positive inflammatory markers (erythrocyte sedimentation rate \[ESR\], high-sensitivity C-reactive protein \[hs-CRP\], interleukin-6 \[IL-6\], tumor necrosis factor-alpha \[TNF-α\], et al; at least twice, ≥ 12 weeks apart), or (B) Positive autoantibodies (at least twice, ≥ 12 weeks apart), or (C) Established diagnosis of chronic inflammatory diseases (autoimmune disease, systemic vasculitis, psoriasis, tuberculosis, et al), or (D) Receiving immunosuppressive therapy (glucocorticoids, immunosuppressive agents, et al).
4. NOT meeting the clinical diagnostic criteria for IR-CAD, including: (1) Hospitalization due to myocardial ischemia, including: (A) Typical symptoms of angina (Canadian Cardiovascular Society \[CCS\] III-IV), and (B) Non-invasive evidence of myocardial ischemia; (2) Angiographic evidence of new or worsened coronary lesions (de novo or restenotic) considered relevant to myocardial ischemia, which occurred: (A) Within 6 months of last coronary angiography in any patients, or (B) Within 12 months of last coronary angiography in patients receiving immunosuppressive therapy within 24 months.
5. Received, or are receiving, or will receive the 24-month clinical follow-up defined by the clinical follow-up protocol for INR-CAD.

Exclusion Criteria:

1. Other moderate to severe heart diseases (congenital heart disease, valvular heart disease, myocarditis, cardiomyopathy, pericardial diseases, pulmonary hypertension, heart failure, arrhythmia, et al).
2. Active malignancy (diagnosed within 12 months or with ongoing requirement for treatment).
3. Vital organ failure.
4. Life expectancy \< 1 year.
5. In pregnancy or breast-feeding, or with intention to be pregnant during the study period.
6. Risk of non-compliance (history of drug addiction or alcohol abuse, et al).
7. Previous enrollment in this study.
8. Participation in another study within 30 days.
9. Involvement in the planning and conduct of this study (applying to investigators, contract research organization staffs, study site staffs, et al).
10. Any condition, which in the opinion of the investigators, would make it unsuitable for the patient to participate in this study.

Primary outcomes:
measure: Major adverse cardiovascular events (MACE)
timeFrame: From the beginning (diagnosis of INR-CAD) to the end of the 24-month clinical follow-up.
Secondary outcomes:
measure: Death
timeFrame: From the beginning (diagnosis of INR-CAD) to the end of the 24-month clinical follow-up.
measure: Q-wave myocardial infarction
timeFrame: From the beginning (diagnosis of INR-CAD) to the end of the 24-month clinical follow-up.
measure: Unplanned myocardial ischemia-driven coronary revascularization
timeFrame: From the beginning (diagnosis of INR-CAD) to the end of the 24-month clinical follow-up.
measure: Unplanned myocardial ischemia-driven hospitalization
timeFrame: From the beginning (diagnosis of INR-CAD) to the end of the 24-month clinical follow-up.
measure: Walking distance in 6 minutes
timeFrame: At the beginning (diagnosis of INR-CAD) and the end of the 24-month clinical follow-up.
measure: Target lesion minimal lumen area (TL-MLA)
timeFrame: At the beginning (diagnosis of INR-CAD) and the end of the 24-month clinical follow-up.
measure: Target lesion percent area stenosis (TL-%AS)
timeFrame: At the beginning (diagnosis of INR-CAD) and the end of the 24-month clinical follow-up.
measure: SYNTAX score
timeFrame: At the beginning (diagnosis of INR-CAD) and the end of the 24-month clinical follow-up.
measure: Number of vessel segments with coronary lesions
timeFrame: At the beginning (diagnosis of INR-CAD) and the end of the 24-month clinical follow-up.
measure: Erythrocyte sedimentation rate (ESR)
timeFrame: At the beginning (diagnosis of INR-CAD) and the end of the 24-month clinical follow-up.
measure: High-sensitivity C-reactive protein (hs-CRP)
timeFrame: At the beginning (diagnosis of INR-CAD) and the end of the 24-month clinical follow-up.
measure: Interleukin-6 (IL-6)
timeFrame: At the beginning (diagnosis of INR-CAD) and the end of the 24-month clinical follow-up.
measure: Tumor necrosis factor-alpha (TNF-α)
timeFrame: At the beginning (diagnosis of INR-CAD) and the end of the 24-month clinical follow-up.
Other outcomes:
measure: Major bleeding events
timeFrame: From the beginning (diagnosis of INR-CAD) to the end of the 24-month clinical follow-up.
measure: Severe infection events
timeFrame: From the beginning (diagnosis of INR-CAD) to the end of the 24-month clinical follow-up.
Locations:
city: Beijing
country: China
facility: Peking Union Medical College Hospital
state: Beijing
Study officials:
References: