In-stent restenosis (ISR) remains a challenging complication following percutaneous coronary intervention (PCI), owing to its complex pathogenesis and multifaceted risk factor profile. We performed a retrospective analysis of all PCI data recorded in the Victorian Cardiac Outcomes Registry (VCOR), from 2013 to 2022, dividing patients into the ISR or de novo-PCI groups based on the intervened lesion. The primary outcome was in hospital mortality, with secondary outcomes including 30-day major adverse cardiovascular events and long-term mortality. Among 104,722 total PCI procedures, 4,935 procedures (4.7%) were for ISR, and 99,787 procedures (95.3%) were for de novo coronary lesions. Patients with ISR were older (mean age 69.0 ± 10.7 years vs. 66.4 ± 11.9 years, p < 0.001) with a higher burden of comorbidities including advanced chronic kidney disease (eGFR less than 31ml/min/1.73m 2 (4.2% vs. 2.5%, p < 0.001)), peripheral vascular disease (6.3% vs. 3.3%, p < 0.001) and diabetes mellitus (34.8% vs. 22.3%, p < 0.001). Lesion complexity was higher in the ISR group, with more lesions classified as ACC/AHA Type B2 and above (74.8% vs. 59.6%, p < 0.001). Adjunctive imaging devices were more commonly utilized in the ISR group; however, use was generally low (8.4% vs. 2.8%, p < 0.001). In-hospital mortality was lower in the ISR group, whereas 30-day target vessel and lesion revascularization rates were higher (1.3% vs. 0.7%, p < 0.001 and 0.8% vs. 0.4%, p = 0.001 respectively). Long term mortality as assessed over 10 years was higher in the ISR group. In conclusion, compared with de novo PCI, patients undergoing ISR PCI were older with greater comorbidities and lesion complexity. ISR PCI was associated with lower in-hospital mortality but worse long-term survival. These findings provide contemporary, population-based evidence on the evolving clinical profile and outcomes of ISR in routine PCI practice.
Despite advancements in drug eluting stent (DES) technologies and intravascular imaging, in-stent restenosis (ISR) remains an infrequent but important cause of recurrent coronary artery stenosis following percutaneous coronary intervention (PCI), with the need for target lesion revascularization (TLR) in ISR estimated at 1% to 2% per year. , PCI for ISR has been associated with higher rates of major adverse cardiovascular events (MACE) and mortality compared to PCI performed for de novo coronary artery disease (CAD). ,,,, ISR lesions often involve complex histopathological mechanisms such as neointimal hyperplasia, neo atherosclerosis, or mechanical stent failure. , Additionally, patients with ISR tend to have higher rates of comorbidities such as diabetes mellitus and impaired renal function. As a result, PCI for ISR can presents a greater clinical and procedural challenge compared with PCI for de novo CAD. Despite its clinical significance and growing recognition as a distinct entity in the modern PCI era, most studies have examined ISR in isolation, with limited direct comparisons to de novo coronary lesions in terms of clinical characteristics, predictors, and outcomes. This study aims to provide contemporary insights into the differing clinical profiles, procedural characteristics, and short- and long-term outcomes of PCI for ISR versus de novo CAD in a large cohort of contemporary patients.
Methods
The Victorian Cardiac Outcomes Registry (VCOR) is a comprehensive, state-wide clinical quality registry designed to monitor and improve cardiovascular care for patients undergoing PCI in Victoria, Australia. Coordinated by Monash University and governed by a multidisciplinary steering committee, VCOR captures data from all 33 public and private hospitals across the state. VCOR methodology has been described previously. For this study, we analyzed all adult patients who underwent PCI recorded in VCOR over a 10-year period, from 1 January 2013 to 31 December 2022. Included patients were divided into two groups– PCI for ISR lesions and PCI for de novo lesions. ISR was defined as a luminal narrowing of greater than 50% within and including up to 5mm proximally and distally from the edge of a pre-existing intracoronary stent, in accordance with the Academic Research Consortium (ARC) definition. ,, This analysis was conducted based on the first lesion treated in each patient. multivessel PCI, whilst representing the minority of the cohort, were not excluded. For classification, patients were assigned to the ISR cohort if any treated lesion met criteria for ISR, even if additional de novo lesions were treated during the same procedure. Patients were classified in the de novo group only if no ISR lesions were treated.
Baseline demographic and clinical characteristics were assessed and compared between the ISR and de novo patient groups. intraprocedural data such as lesion characteristics, type of intervention to lesion, adjunctive devices used, adjuvant antiplatelet or anticoagulant therapy and procedural success rate, were collected and compared. Intraprocedural success has been defined as having met both criteria of residual stenosis <10% following coronary stenting or <50% following balloon angioplasty/atherectomy and TIMI 2 or TIMI 3 flow post intervention. Lesion complexity was classified in accordance with American College of Cardiology/American Heart Association (ACC/AHA) guidelines, categorized as Type A, B1, B2, or C.
Clinical outcomes assessed at 30 days postprocedure was obtained directly from the VCOR database. These included all-cause mortality, occurrence of new stroke, major bleeding events, unplanned or emergency PCI, repeat revascularization of the target vessel or lesion (TLR), as well as the requirement for emergency coronary artery bypass grafting (CABG). Long-term mortality data was obtained through linkage with the Australian National Death Index (NDI), a comprehensive national database managed by the Australian Institute of Health and Welfare. The NDI aggregates death records from all state and territory registries and includes both the date and cause of death, allowing for reliable tracking of mortality outcomes over time.
Categorical variables were presented as frequencies and proportions, and continuous variables were reported as mean ± standard deviation for normally distributed data, and otherwise as median with interquartile range. Appropriate statistical tests were used based on data distribution, including the t-test or Chi-square test accordingly. Long-term mortality data from the NDI was used to generate Kaplan–Meier survival curves for ISR and de novo groups, with differences assessed using the log-rank test. Multivariable logistic regression was performed to evaluate both unadjusted and adjusted associations, identify potential confounders, and assess the independent effect of each variable on clinical outcomes. Variables included in the multivariable model were selected based on clinical relevance and statistical significance in univariable analyses, and comprised: age, sex, body mass index (BMI), diabetes mellitus, peripheral vascular disease (PVD), cerebrovascular disease, previous CABG, estimated glomerular filtration rate (eGFR) category, left ventricular ejection fraction (LVEF) category, presentation diagnosis and cardiogenic shock. All statistical tests were two-tailed, with a p-value <0.05 considered statistically significant. Missing data was infrequent, and multivariable models were constructed using complete-case analysis—patients with missing values were not included. Statistical analysis was conducted using Stata version 17.0 (Stata Corporation, College Station, TX, USA).
Results
A total of 104,722 PCI procedures were recorded in VCOR between 2013 and 2022, comprising 4,935 (4.7%) cases of PCI for ISR and 99,787 (95.3%) cases of PCI for de novo coronary artery disease.
Patients in the ISR cohort were significantly older than those in the de novo group (69.0 ± 10.7 years vs. 66.4 ± 11.9 years, p < 0.001) and were less likely to be female (20.2% vs. 24.1%, p < 0.001) ( Table 1 ). The ISR group demonstrated a greater burden of comorbidities, including higher rates of diabetes mellitus (34.8% vs. 22.3%, p < 0.001), PVD (6.3% vs. 3.3%, p < 0.001), cerebrovascular disease (4.7% vs. 3.4%, p < 0.001), and previous CABG (15.1% vs. 6.5%, p < 0.001). Renal dysfunction was also more common, with a higher proportion of patients having eGFR ≤30 ml/min/1.73 m² (4.2% vs. 2.5%, p < 0.001). ISR patients were more likely to present with chronic coronary syndromes (61.1% vs. 49.3%, p < 0.001), and less likely with ST-Elevation Myocardial Infarction (STEMI) (6.6% vs. 21.2%, p < 0.001).
Table 1
Patient demographics and baseline characteristics
| Characteristic | All (n = 104,722) | ISR (n = 4,935) | De Novo (n = 99,787) | p-Value |
|---|---|---|---|---|
| Age (y) | 66.6 ± 11.9 | 69 ± 10.7 | 66.4 ± 11.9 | <0.001 |
| Female gender | 24,899 (23.9%) | 995 (20.2%) | 24,003 (24.1%) | <0.001 |
| Private hospital | 43,323 (41.4%) | 2,542 (51.5%) | 40,781 (40.9%) | <0.001 |
| Median length of stay (IQR) | 2.0 (1.0, 4.0) | 2.0 (1.0, 4.0) | 2.0 (1.0, 4.0) | <0.001 |
| Median BMI (kg/m 2) (IQR) | 28.0 (25.1, 31.6) | 28.4 (25.3, 32.0) | 28.0 (25.1, 31.6) | <0.001 |
| Diabetes mellitus | 23,930 (22.9%) | 1,717 (34.8%) | 22,213 (22.3%) | <0.001 |
| Peripheral vascular disease | 3,620 (3.5%) | 313 (6.3%) | 3,307 (3.3%) | <0.001 |
| Cerebrovascular disease | 3,641 (3.5%) | 234 (4.7%) | 3,407 (3.4%) | <0.001 |
| Previous CABG | 7,243 (6.9%) | 747 (15.1%) | 6,496 (6.5%) | <0.001 |
| LVEF | <0.001 | |||
| Normal (≥50%) | 62,211 (59.4%) | 2,816 (57.1%) | 59,395 (59.5%) | |
| Mild (45% to 49%) | 15,608 (14.9%) | 634 (12.8%) | 14,974 (15.0%) | |
| Moderate (35% to 44%) | 9,251 (8.8%) | 391 (7.9%) | 8,860 (8.9%) | |
| Severe (<35%) | 4,557 (4.4%) | 192 (3.9%) | 4,365 (4.4%) | |
| Renal Function | <0.001 | |||
| eGFR >60 ml/min/1.73m 2 | 75,938 (72.5%) | 3,408 (69.1%) | 72,530 (72.7%) | |
| eGFR 31-60 ml/min/1.73m 2 | 18,079 (17.3%) | 1,021 (20.7%) | 17,058 (17.1%) | |
| eGFR ≤30 ml/min/1.73m 2 | 2,705 (2.6%) | 205 (4.2%) | 2,500 (2.5%) | |
| Cardiogenic shock or OOHCA | 2,838 (2.7%) | 55 (1.1%) | 2,783 (2.8%) | <0.001 |
| Indication for PCI | <0.001 | |||
| STEMI | 21,451 (20.5%) | 327 (6.6%) | 21,124 (21.2%) | |
| NSTEMI | 24,491 (23.4%) | 1,118 (22.7%) | 23,373 (23.4%) | |
| UAP | 6,526 (6.2%) | 475 (9.6%) | 6,051 (6.1%) | |
| Non-ACS | 52,254 (49.9%) | 3,015 (61.1%) | 49,239 (49.3%) |
Values are expressed as mean ± standard deviation or n (%).
ACS = acute coronary syndrome; BMI = body mass index; CABG = coronary artery bypass graft; eGFR = estimated glomerular filtration rate; ISR = in-stent restenosis; LVEF = left ventricular ejection fraction; NSTEMI = non-ST-elevation myocardial infarction; PCI = percutaneous coronary intervention; STEMI = ST-elevation myocardial infarction; UAP = unstable angina pectoris.
ISR lesions were more complex than de novo lesions, with a higher proportion classified as ACC/AHA Type B2 or C (74.8% vs. 59.6%, p < 0.001) ( Table 2 ). The use of adjunctive imaging modalities such as intravascular ultrasound (IVUS) and optical coherence tomography (OCT) was low, but by comparison more common in the ISR group (8.4% vs. 2.8%, p < 0.001). Femoral access was used more frequently in ISR cases (47.7% vs. 36.7%, p < 0.001). Drug-eluting balloons (DEB) were deployed in 16.0% of ISR cases compared to 0.4% in de novo lesions (p < 0.001), and plain balloon angioplasty (POBA) alone was used in 22.6% of ISR cases versus 3.0% of de novo cases (p < 0.001). Overall procedural success was similar between the groups (91.7% in both, p = 0.88).
Table 2
Procedural characteristics
| Characteristic | All (n = 104,722) | ISR (n = 4,935) | De Novo n = 99,787) | p-Value |
|---|---|---|---|---|
| Femoral access | 39,002 (37.2%) | 2,353 (47.7%) | 36,649 (36.7%) | <0.001 |
| IVUS or OCT | 3,187 (3.0%) | 417 (8.4%) | 2,770 (2.8%) | <0.001 |
| FFR | 2,652 (2.5%) | 112 (2.3%) | 2,540 (2.5%) | 0.23 |
| Lesion location | <0.001 | |||
| RCA | 31,284 (29.9%) | 1,670 (33.8%) | 29,614 (29.7%) | |
| LAD | 44,032 (42.0%) | 1,806 (36.6%) | 42,226 (42.3%) | |
| LCx | 25,486 (24.3%) | 1,119 (22.7%) | 24,367 (24.4%) | |
| LM | 2,219 (2.1%) | 132 (2.7%) | 2,087 (2.1%) | |
| Graft | 1,701 (1.6%) | 208 (4.2%) | 1,493 (1.5%) | |
| Lesion complexity | <0.001 | |||
| A | 7,765 (7.4%) | 171 (3.5%) | 7,594 (7.6%) | |
| B1 | 33,804 (32.3%) | 1,068 (21.6%) | 32,736 (32.8%) | |
| B2 | 35,722 (34.1%) | 1,921 (38.9%) | 33,801 (33.9%) | |
| C | 27,427 (26.2%) | 1,774 (35.9%) | 25,653 (25.7%) | |
| Procedural success | 96,060 (91.7%) | 4,524 (91.7%) | 91,536 (91.7%) | 0.88 |
| Device type | <0.001 | |||
| DES | 92,482 (88.3%) | 3,652 (74.0%) | 88,830 (89.0%) | |
| BMS | 5,285 (5.0%) | 43 (0.9%) | 5,242 (5.3%) | |
| BVS/Other stent | 259 (0.3%) | 4 (0.1%) | 255 (0.3%) | |
| POBA only | 4,132 (3.9%) | 1,117 (22.6%) | 3,015 (3.0%) | |
| Any DEB | 1,230 (1.2%) | 792 (16.0%) | 438 (0.4%) | <0.001 |
| DEB only | 914 (0.9%) | 612 (12.4%) | 302 (0.3%) | <0.001 |
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