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Predictive Score for Target Vessel Revascularization after Bare Metal Coronary Stenting
January 2006
Drug-eluting stents (DES) significantly decrease the need for a new target vessel revascularization (TVR) after coronary intervention,1–4 but its widespread use is still limited by cost issues.5,6 DES are currently used in more than 70% of percutaneous coronary interventions (PCI) performed in the United States,7 but in less than 50% of procedures in most other countries. The reasons behind this “selective approach” are not only the high cost of DES when compared to bare metal stents (BMS), but also the belief that restenosis can be reasonably predicted by clinical and angiographic characteristics identified before stent implantation.
Indeed, prediction of restenosis after PCI is one of the most studied topics in interventional cardiology.8–13 We previously reported in this journal an angiographic score to predict restenosis after balloon coronary angioplasty, which identified subgroups of patients with very low (less than 5%) or very high (approximately 80%) restenosis rates.14 Predictive models for restenosis after coronary stenting have also been developed, but the results were not consistent in various studies.12,13 The main purpose of this study is to describe a new score to predict TVR after BMS implantation, which is simple to recall and easy to use in daily clinical practice.
Methods
Patients. All patients undergoing PCI with coronary stents as treatment for symptomatic coronary artery disease at our institution between June 1997 and December 2001 were potential candidates for inclusion in this study. Excluded from the study were those with cardiogenic shock, in-stent restenosis or who underwent unsuccessful procedures. Unsuccessful procedures were defined as those with significant residual stenosis (> 30%) or with impaired coronary flow (TIMI 0 to 1) after stent implantation, and those associated with major cardiovascular events during hospitalization or when the stent did not cross the index lesion.
The study was approved by the appropriate institutional review board and all participants provided signed informed consent. All test results were reviewed by one investigator who was unaware of the clinical data and blinded to the outcome assessment. All data were prospectively recorded on standard forms and analyzed using SPSS software for Windows 11.0.
Clinical presentation. At entry, all patients had a coronary syndrome that was characterized as stable angina, unstable angina in most, or myocardial infarction. Stable angina was defined as the maintenance of the patient’s angina pattern within the last two months of the intervention. Unstable angina was defined as worsening of the intensity and/or frequency of the angina pattern within two months of stenting. Acute myocardial infarction (AMI) was defined as ongoing chest pain and ST-segment elevation that prompted referral for percutaneous revascularization of an infarct-related artery.
Indications for stenting included elective procedures, provisional stenting procedures and salvage procedures. Elective procedures were those planned. Provisional stenting procedures were those needed due to suboptimal results of a coronary angioplasty procedure (i.e., large nonocclusive dissections, residual lesions > 50%, or elastic recoil). Salvage procedures were those performed during an episode of acute occlusion. A stenting procedure was considered successful if it resulted in no major coronary events (MACE: death, AMI, new revascularization procedure during the patient’s in-hospital stay).
Implantation procedure. All patients were receiving oral platelet inhibitors, aspirin (100–200 mg daily) and ticlopidine (250 mg twice daily) at the time of PCI. In urgent cases, these drugs were administered during or soon after stenting. Intravenous boluses of heparin were administered during the implantation procedure itself. Lesions were treated using standard PCI techniques.15 In most cases, treatment involved balloon dilatation followed by stent placement. In each case, the treating physician decided the type and how many stents to use, whether to use high pressure, and whether to use any other devices or glycoprotein IIb/IIIa inhibitors.
Angiographic analysis. All angiographic analyses were performed in at least two different views by experienced operators with a previously validated DCI-S digital caliper system (Phillips America North America Co., Bothell, Washington). Target vessel diameter was defined as the mean diameter of the luminal segments proximal and distal to the lesion. The severity of stenosis was measured in two orthogonal views. Lesion length was measured “shoulder-to-shoulder”. Longer lesions were considered a single lesion only when a normal segment 16
Follow-up and study endpoints. Patients were followed up for one year either by clinical evaluation in an outpatient clinic, by interview with the attending physician or by telephone contact. Control angiography was performed only when symptoms or signs of recurrent myocardial ischemia were present. Clinical, procedural and angiographic characteristics and in-hospital follow-up data regarding the study population were recorded and prospectively entered into a dedicated database. The need for a new TVR in the one-year period after the index stenting procedure [either by coronary artery bypass grafting (CABG) or by PCI] was registered. All MACE occurring during the in-hospital period, out-of-hospital period, and the first year after stenting, were also recorded in the database.
Statistical analysis. Categorical variables were expressed as percentiles and continuous variables were expressed as the mean ± standard deviation (SD). Differences between the patients with or without a new TVR procedure were evaluated by the c2 test (categorical variables) and by the Student’s t-test (continuous variables). The clinical, angiographic and procedural characteristics of patients with or without a new TVR in the one-year clinical follow-up were compared. Variables with statistical significance in the univariate analysis or those previously reported as having a strong association with clinical restenosis were entered into a multiple logistic regression model in order to identify independent predictors of one-year TVR. Next, separate models were created and compared by means of the Hosmer-Lemehow goodness-of-fit test to determine which one most appropriately fit the data (e.g., which model had the lowest c2 value and the highest p-value, which indicate a similarity between observed and calculated values).10,17 The model with the best discriminatory ability was chosen. Continuous variables were transformed into categorical, and cutpoints were determined according to frequency histogram examination. The points in the risk score were assigned proportionately to the relative risks of a new TVR.
Results
Patients. In the study period, 876 consecutive patients met the inclusion criteria, and one-year clinical follow-up was complete in 97% of the cases. We analyzed only the 848 patients with one-year clinical follow-up who underwent 895 stent implantations. There were no statistically significant differences between the clinical, angiographic or procedural characteristics of patients with or without one-year clinical follow-up. The one-year TVR rate in our study was 7.4%, and a new PCI was performed in 5% of the patients and CABG in 2.8%. The one-year myocardial infarction rate was 2.9%, death occurred in 2.4% of patients, and the total one-year MACE rate was 9.2%.
Patients with a new TVR (n = 63) were significantly younger than those without a new TVR (n = 785) (56.56 ± 11.73 years vs. 60.27 ± 10.70 years; p = 0.009), and there was a trend toward a higher proportion of males in this group (81% vs. 71%; p = 0.08). Diabetes mellitus was more prevalent in patients who underwent a new TVR (30% vs. 22%), but this difference did not achieve statistical significance (p = 0.21). Acute coronary syndrome, with or without ST-segment elevation (87% vs. 76%; p = 0.03), and a previous coronary angioplasty (17% vs. 8%; p = 0.02) were also more frequent in patients with a new TVR (Table 1).
Angiographic and procedural characteristics. Patients who required another TVR in the first year after stenting were more frequently treated for ostial lesions than those without a new TVR (4% vs. 1%; p = 0.01). The extent of coronary artery disease, the target vessel intervened on and lesion characteristics, were not statistically different among both groups. The majority of patients studied underwent elective stenting (60% vs. 58%; p = 0.85). Most patients received one of the following stents: Multi-Link Tristar™ (Guidant Corp., Indianapolis, Indiana) or Multi-Link Tetra™ (Guidant) (33%), Tenax™ (Biotronik, Berlin, Germany) or Teneo (Biotronik) (28%) or BX Velocity™ (Cordis Corp., Miami, Florida) (10%). There were no statistically significant differences regarding the type of stents used in both groups. The mean target vessel diameter was significantly lower in patients with TVR than in the control group (3.18 ± 0.32 mm vs. 3.32 ± 0.43 mm; p = 0.001), as was the lesion length (11.70 ± 5.67 mm vs. 10.08 ± 4.54 mm; p = 0.03). The implantation pressure, stent length, minimum luminal diameter before stent implantation and percent stenosis were not statistically different between both groups. The final luminal diameter was lower in patients who needed a new TVR (3.20 ± 0.33 mm vs. 3.35 ± 0.40 mm; p = 0.003) (Tables 2 and 3).
Multivariate analysis. The variables included in the multiple logistic regression model were sex, previous angioplasty, age, reference vessel diameter, lesion length, unstable coronary syndrome and diabetes mellitus (Table 4). Acute coronary syndrome, reference vessel diameter, lesion length and diabetes mellitus were retained, and separate models were constructed and compared by means of the Hosmer-Lemeshow goodness-of fit test (Table 5). Diabetes mellitus was also included because it was previously demonstrated to be associated with TVR in several important clinical and experimental studies. The results demonstrate that the model that most appropriately fit the data included the reference vessel diameter, lesion length and diabetes mellitus (Hosmer-Lemeshow goodness-of-fit statistic = 2.339; p = 0.969). Of note, the withdrawal of diabetes mellitus from the model caused a significant increase in the Hosmer-Lemeshow goodness-of-fit statistic (from 2.339; p = 0.969 to 6.839; p = 0.554), which demonstrates its importance.
Score. The reference vessel diameter was stratified into vessels smaller than 3 mm, those measuring 3.0–3.5 mm, and vessels larger than 3.5 mm. The TVR rate increased proportionately to each tertile ( 3.5 mm = 9.8%; p = 0.02). The lesion length was stratified into lesions less than 10 mm in length, those measuring 10–20 mm in length and lesions longer than 20 mm. The TVR rate increased with each level ( 20 mm = 15.6%; p = 0.02). These cutoffs were chosen because they provided an adequate division of the sample and a proportionate increase in TVR rates in each subgroup. In addition, diabetes was considered present or not. The risk score was calculated by assigning a value to each variable according to the relative risk ratio of one-year TVR: 1) Diabetes mellitus: present = 1 point; and absent = 0 points; 2) reference vessel diameter: 3.5 mm = 0 points; and 3) lesion length: rp p-value of the Chi-square test for trend was 8–13,18–26 We believe that the inclusion of variables obtained before stenting is especially important, because it can contribute to the decision to use a drug-eluting stent or a bare metal stent.
Many studies have demonstrated that patients who have good clinical outcomes after PCI can be identified based on angiographic and clinical characteristics. We previously reported an angiographic score predictive of restenosis after coronary angioplasty, based on the lesion length, lesion irregularity, post-dilatation haziness and residual stenosis. This score stratified subgroups of patients with very low ( 80%) restenosis rates.14 Ellis and coworkers12 reported on their experience with 5,239 consecutive patients treated with bare metal coronary stents at the Cleveland Clinic. A new coronary revascularization, either in the vessel stented or not, was required in 13.4% of the patients in the 9-month clinical follow-up. The reference vessel diameter, lesion length, unstable angina and ostial lesions, among others, were identified as strong predictors of a new revascularization procedure. The rate of reintervention in patients without unstable angina and with lesions shorter than 10 mm located in vessels larger than 3.5 mm was less than 3%. Greenberg and coworkers6 developed a logistic regression model to predict clinical restenosis after bare metal stenting as a function of lesion length, reference vessel diameter and diabetes mellitus, based on a cohort of 4,227 patients without routine angiographic follow-up. In this model, the estimated risk of a new TVR for a non-diabetic patient with stent implantation in a 10 mm lesion of a 3.5 mm vessel was 5%, while a stent placed in a 20 mm long lesion in a 2.5 mm vessel of a diabetic patient would have an expected clinical restenosis rate of 24%. On the other side, the analysis of the 1,312 patients included in the angiographic substudy of the PRESTO trial showed a much higher restenosis rate (46%).13 These authors also explored the predictive ability of candidate variables from available studies and from the PRESTO trial, but the scores developed had only modest predictive ability for restenosis after PCI.
It is important to consider that our study showed a low overall clinical restenosis rate (7.4%) when compared to available studies. This low rate is probably related to the large mean reference vessel diameter (3.31 ± 0.43 mm) and to the low mean lesion length (10.20 ± 4.66 mm) of the vessels treated in our cohort of patients. The absence of routine angiographic follow-up was also reported to be associated with lower rates of new revascularization procedures in previous studies.27 Indeed, our results fit adequately with the expected restenosis rates according to the models developed by Greenberg and Serruys.6,10
The clinical implications of this study relate to the prediction of a new TVR after coronary stenting based on preprocedural characteristics, which can aid to the decision to implant a drug-eluting or a bare metal stent. We believe that patients with predicted low or very low TVR rates (6,28,29
Study limitations. Considering the applicability of this score, we acknowledge that our patient cohort had a high proportion of patients with large vessels and short lesions, which influenced the overall target vessel revascularization rate. While our score had a very good fit to this sample, as demonstrated by the Hosmer-Lemeshow goodness-of-fit test, it remains to be seen if it will perform equally well in more challenging subsets of patients (e.g., patients with longer lesions and smaller vessels). In this case, it could be necessary to include another subgroup classification, such as vessels smaller than 2.5 mm and lesions longer than 30 mm.
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