Predictors of in-stent restenosis in patients undergoing percutaneous coronary intervention
İsmail Polat Canbolat1, Alev Arat-Özkan2
1Department of Cardiology, Demiroglu Bilim University Faculty of Medicine, Istanbul, Turkey
2Department of Cardiology, Istanbul University Cerrahpaşa Faculty of Medicine, Istanbul, Turkey
Keywords: Bare-metal stent, drug-eluting stent, in-stent restenosis
Objectives: Clinical, angiographic, and biochemical factors associated with in-stent restenosis were retrospectively analyzed in patients undergoing percutaneous coronary intervention.
Materials and methods: Patients who had undergone follow-up angiography for de novo lesions six months after bare metal stent (BMS) and nine months after drug eluting stent (DES) implantation were retrospectively analyzed. Demographic, angiographic, and clinical parameters were collected from our patient database: In-stent restenosis (ISR) was defined as >50% narrowing of stent lumen or coronary artery 5 mm adjacent to stent edges. Retrospectively 319 patients with a mean age of 57.6 years were included in this study.
Results: In-stent restenosis occurred in 26.6% of the patients with drug-eluting stent and 36.5% of the patients with bare-metal stent implanted. Tobacco use was significantly more frequent among patients with in-stent restenosis.
Conclusion: In-stent restenosis rates in our study is consistent with the literature. Studies are ongoing to overcome this challenging problem.
Percutaneous coronary intervention (PCI) is the most commonly preferred approach in most patients. In-stent restenosis (ISR), defined as >50% narrowing of stent lumen or coronary artery 5 mm adjacent to stent edges, is a restricting complication of PCI leading to repeat revascularization. Inflammation, patient characteristics, and mechanical factors have been characterized as predictors of ISR.[6-9]
In this study, we retrospectively analyzed the effect of clinical, angiographic, and biochemical factors on ISR in patients who underwent PCI.
Patients and Methods
Patients who had undergone control angiogram six months after bare metal stent (BMS) and nine months after drug eluting stent (DES) implantation for de-novo lesions at Istanbul University Cardiology Institute between October 2007-April 2008 and January 2011- April 2012 were retrospectively analyzed. Patients without control angiogram (n=181),
patients with only coronary balloon angioplasty (n=46), and stent implantation to bypass graft veins (n=20) were excluded from the study. Demographic, angiographic, and clinical parameters were collected from our patient database: Gender, age, primary indication for PCI, creatinine, diabetes mellitus (DM), history of coronary artery disease (CAD), history of heart failure, history of cerebrovascular disease, dyslipidemia, tobacco use, and hypertension. In-stent restenosis (ISR) was defined as >50% narrowing of stent lumen or coronary artery 5 mm adjacent to stent edges.
The study was conducted with the approval of the Local Research Ethics Committee. A written informed consent was obtained from each patient. The study was conducted in accordance with the principles of the Declaration of Helsinki.
Continuous variables were expressed as mean ± standard deviation and categorical variables were expressed as percentage (%). Categorical variables were compared using the chi-square test. Student’s t-test was used to compare the continuous variables. All analyses were performed using SPSS for Windows version 15.0 software (SPSS, Inc., Chicago, Illinois, USA). A two-sided value less than 0.05 was considered statistically significant within a 95% confidence interval (CI).
A total of 319 patients with a mean age of 57.6 years were included in this retrospective study. Demographic and clinical characteristics are presented in Table 1. The angiographic characteristics of our patient population is demonstrated in Table 2. In-stent restenosis occurred in 99 patients (31%) of the entire group. Patients were divided into two groups according to ISR. Table 3 compares the clinical characteristics of patients with and without ISR. Table 4 compares the angiographic characteristics of patients with and without ISR. Tobacco usage was significantly more frequent among patients with ISR. Dyslipidemia was significantly more common in patients without ISR. There was no difference in angiographic and stent characteristics between the groups.
In this study, factors associated with ISR were investigated in our population. In our study, ISR prevalence was 31%. In-stent restenosis occurred in 26.6% of the patients with DES and 36.5% with BMS. Although there is limited data on the prevalence of ISR in our country, ISR occurred in 27.9% of patients who underwent BMS implantation in our clinic between 1995 and 1996. Drug-eluting stents were developed to lower the frequency of ISR. In our study population, although patients with DES implantation had lower rate of ISR, this difference did not attain significance. High rate of ISR in the DES group may be attributed to smaller stent diameter, longer stents, and complex coronary interventions.
Previous studies have reported female gender is associated with higher rates of ISR, however, in our study, there was no significant difference between genders according to ISR.
Use of tobacco leads to endothelial disfunction, inflammation, and aggravation of cardiovascular disease.[12,13] Turak et al. investigated the role of neutrophil/lymphocyte ratio in predicting BMS restenosis and reported smoking was an associated factor of ISR. In our study, tobacco use was significantly more common in patients with ISR although we did not have any data on continuous tobacco use until follow-up angiography.
Patients with dyslipidemia in our study group had significantly lower rates of ISR. This finding seemed conflicting as statins have a protective effect on neointimal hyperplasia and this finding may be attributed to statin use among patients with dyslipidemia.
We investigated the target vessel as a potential factor for ISR. Stent implantation of the left anterior descending artery showed predisposition towards ISR.
In conclusion, the ISR rates determined in our study was consistent with the literature. Studies are ongoing to overcome this challenging problem.
The authors declared no conflicts of interest with respect to the authorship and/or publication of this article.
The authors received no financial support for the research and/or authorship of this article.
- Townsend N, Nichols M, Scarborough P, Rayner M. Cardiovascular disease in Europe--epidemiological update 2015. Eur Heart J 2015;36:2696-705.
- Weir HK, Anderson RN, Coleman King SM, Soman A, Thompson TD, Hong Y, et al. Heart Disease and Cancer Deaths - Trends and Projections in the United States, 1969-2020. Prev Chronic Dis 2016;13:E157.
- Mallika V, Goswami B, Rajappa M. Atherosclerosis pathophysiology and the role of novel risk factors: a clinicobiochemical perspective. Angiology 2007;58:513-22.
- Libby P. Inflammation in atherosclerosis. Nature 2002;420:868-74.
- Neumann FJ, Sousa-Uva M, Ahlsson A, Alfonso F, Banning AP, Benedetto U, et al. 2018 ESC/EACTS Guidelines on myocardial revascularization. Eur Heart J 2019;40:87-165.
- Rajagopal V, Rockson SG. Coronary restenosis: a review of mechanisms and management. Am J Med 2003;115:547-53.
- Bennett MR. In-stent stenosis: pathology and implications for the development of drug eluting stents. Heart 2003;89:218-24.
- El-Omar MM, Dangas G, Iakovou I, Mehran R. Update on In-stent Restenosis. Curr Interv Cardiol Rep 2001;3:296-305.
- Cutlip DE, Chauhan MS, Baim DS, Ho KK, Popma JJ, Carrozza JP, et al. Clinical restenosis after coronary stenting: perspectives from multicenter clinical trials. J Am Coll Cardiol 2002;40:2082-9.
- Gurmen T, Babalik E, Gulbaran M, Öztürk S, Öztürk M. Intracoronary stent implantation: six months results, predictors of stent restenosis. Arch Turk Soc Cardiol 1998;26:408-15.
- Goldberg SL, Loussararian A, De Gregorio J, Di Mario C, Albiero R, Colombo A. Predictors of diffuse and aggressive intra-stent restenosis. J Am Coll Cardiol 2001;37:1019-25.
- Bermudez EA, Rifai N, Buring JE, Manson JE, Ridker PM. Relation between markers of systemic vascular inflammation and smoking in women. Am J Cardiol 2002;89:1117-9.
- Taylor BV, Oudit GY, Kalman PG, Liu P. Clinical and pathophysiological effects of active and passive smoking on the cardiovascular system. Can J Cardiol 1998;14:1129-39.
- Turak O, Ozcan F, Isleyen A, Tok D, Sokmen E, Buyukkaya E, et al. Usefulness of the neutrophil-to- lymphocyte ratio to predict bare-metal stent restenosis. Am J Cardiol 2012;110:1405-10.
- Walter DH, Schächinger V, Elsner M, Mach S, Auch- Schwelk W, Zeiher AM. Effect of statin therapy on restenosis after coronary stent implantation. Am J Cardiol 2000;85:962-8.
- Kastrati A, Schömig A, Elezi S, Schühlen H, Dirschinger J, Hadamitzky M, et al. Predictive factors of restenosis after coronary stent placement. J Am Coll Cardiol 1997;30:1428-36.