Author + information
- Received February 7, 1996
- Revision received April 18, 1996
- Accepted May 24, 1996
- Published online October 1, 1996.
- ANTONIO COLOMBO*,
- MASSIMO FERRARO,
- AKIRA ITOH,
- GIOVANNI MARTINI,
- SIMONETTA BLENGINO and
- LEO FINCI
- ↵*Address for correspondence: Dr. Antonio Colombo, Centro Cuore Columbus, Via Buonarroti 48, 20145 Milan, Italy.
Objectives. This study attempted to analyze immediate and long-term angiographic and clinical results of coronary stent implantation for restenosis in a consecutive group of patients.
Background. The rate of stent utilization in patients with coronary artery disease has increased exponentially in recent years. There are many unanswered questions about the use of stenting in patients with restenosis, particularly with respect to late clinical and angiographic results.
Methods. A total of 159 stents were implanted in 128 consecutive patients with 139 lesions (mean 1.3 stents/patient). A technique of optimal stent expansion was used in all patients, and intravascular ultrasound guidance with no subsequent anticoagulation was performed in 41 patients.
Results. Stent implantation was successful in 126 patients (98%). Four patients (3.1%) had complications (in two after successful stenting): death in one, emergency bypass surgery operation in two and subacute stent thrombosis in one. Stents were implanted with a final balloon size (mean ± SD) of 3.5 ± 0.5 mm and a mean maximal pressure of 11 ± 4 atm (range 8 to 20). Angiographic restenosis occurred in 27 patients (25%). Regression analysis on clinical and angiographic variables for prediction of restenosis showed no statistical significance for any variable. Late events occurred in 23 patients (19%). The actuarial survival rate was 98% at 1 year and at 3 years, and the event-free survival rate including freedom from repeat angioplasty for restenosis was 95% and 76%, respectively.
Conclusions. The late angiographic outcome, restenosis rate and total clinical events are favorable for selected patients undergoing stent implantation for the indication of restenosis.
Restenosis after percutaneous transluminal coronary angioplasty (PTCA) of a coronary lesion has been reported to have an incidence rate of 17% to 60% . The most common approach to treatment of a restenotic lesion after PTCA has been a repeat balloon dilation procedure. This strategy is associated with a reported 25% to 40% incidence rate of a second restenosis [1–3]. The use of other technologies such as laser angioplasty , directional atherectomy  or rotational atherectomy , has seldom been evaluated as a treatment for restenotic lesions. Although coronary stenting has been studied as a means of preventing restenosis in primary lesions [7, 8], reports concerning its use in treating restenotic lesions are scarce . The reported restenosis rate is as low as 16% after placement of a single stent and has high as 65% after multiple stenting . These data have led to reconsideration of the use of coronary stents for restenosis .
The purpose of this study is to analyze the results of our complete experience of coronary stenting for treatment of restenotic lesions after PTCA.
From November 1989 until June 1994 a total of 723 patients underwent coronary stenting at our institution. The study cohort comprised 128 consecutive patients who underwent coronary stenting to treat a restenotic lesion after successful PTCA. All patients included in this study had at least 12 months of clinical follow-up.
Stenting procedure. Patients were treated with aspirin, 325 mg daily, and calcium channel blocking agents before stenting. A bolus of 10,000 U of heparin was given after sheath insertion and a repeat bolus of 5,000 U was given to maintain the activated clotting time >250 s. The first 80 patients were given dextran during the procedure of stent implantation and dipyridamole after the procedure. Stents were placed only in vessels with a reference diameter >2.5 mm by visual estimation. The coronary Palmaz-Schatz stent (Johnson & Johnson Interventional System), its short version and the Palmaz biliary stent were the stents most frequently implanted. For most procedures these stents were hand-crimped on a PTCA balloon. They were rarely implanted with a dedicated stent delivery system. Occasionally, other stents were used: the Gianturco-Roubin (Cook Inc.), Wiktor (Medtronic Inc.), Micro (Advanced Vascular Engineering, Canada) and Cordis (Cordis Corp.) stents. Use of these stents was restricted to anatomic settings not considered ideal for the slotted tube design; the Gianturco-Roubin stent was sometimes used to treat a long lesion. Stents in this group were implanted with the use of their own delivery system.
After stent implantation, further dilations were performed to obtain a near zero angiographic residual stenosis. The most recent 41 patients underwent intravascular ultrasound (IVUS) evaluation and additional balloon dilations until established criteria for optimal IVUS stent expansion and plaque compression were achieved . Multiple stenting was liberally performed to fully cover the diseased segment. Multiple stents were implanted to ensure minimal overlap and no gaps. In the early period of this experience an oversized balloon was used to perform the final dilation. Since 1993, stents have been placed with IVUS guidance, and optimal results have been achieved with an appropriately sized balloon inflated at high pressure.
IVUS evaluations were performed by utilizing a 3.9 monorail system with a 25-MHz transducer-tipped catheter (Interpret Catheter InterTherapy/CVIS). A Cardiovascular Imaging System (CVIS) with a 2.9F imaging catheter was used during the most recent period of this study.
Angiographic analysis. Coronary angiograms were analyzed by personnel not involved in the stenting procedure and without knowledge of the IVUS results. The vessels and lesions were measured by using digital calipers (Brown and Sharp) from an optically magnified image in a single matched “worst” view. The guiding catheter was used as a reference object for calibration. Minimal lumen diameter (MLD) and percent stenosis were obtained in the baseline, final and follow-up angiograms. The mean reference lumen was calculated as the average of the proximal and distal reference lumens. Lesion length was measured as the distance from the shoulders of the lesion. Lesions were characterized according to the American Heart Association/American College of Cardiology (AHA/ACC) classification. A long lesion was defined as a single continuous narrowing >15 mm in length.
The following variables were calculated from the angiographic analysis: acute gain = MLD after stenting minus MLD before intervention; late loss = MLD after stenting minus MLD at follow-up; relative gain = acute gain divided by reference vessel size; relative loss = late loss divided by reference vessel size; net gain index = (MLD at follow-up minus MLD before stenting) divided by reference vessel size.
Angiographic findings such as thrombus, calcifications, dissections, side branch occlusion and vessel rupture were recorded and analyzed.
Medications after stenting. In the first period of this study, patients were treated with standard postprocedural heparin, started 3 or 4 h after sheath removal and continued until oral anticoagulation with warfarin resulted in prolongation of prothrombin time to an international normalized ratio of 2.0 to 3.5. Warfarin therapy was continued for 1 month in association with aspirin, 325 mg daily. In the most recent period of this study and since performance of stent implantation with IVUS guidance and high pressure dilation, patients received no heparin or oral anticoagulant agents after stent implantation. Aspirin, 325 mg daily, was continued long term and ticlopidine, 250 mg twice daily, was given for 1 month.
The following definitions were used: Primary stent success = stent implantation on the target lesion with <30% residual stenosis and with the patient leaving the cardiac catheterization laboratory alive and free of Q wave myocardial infarction or emergency coronary artery bypass surgery (CABG). Major events = death, CABG, myocardial infarction (Q wave or non-Q wave), emergency PTCA and vascular complications. Death = any death irrespective of cause. Q wave myocardial infarction = presence of a new pathologic Q wave in the electrocardiogram in association with an elevation of cardiac serum enzyme levels to ≥2 times the normal value. Non-Q wave myocardial infarction = absence of new Q waves despite this enzyme elevation. Emergency CABG = surgical revascularization performed after immediate transfer of the patient from the cardiac catheterization laboratory to the operating room or within 24 h. Elective CABG = surgical revascularization performed 24 h after stenting or attempted stenting in the absence of ischemia. Acute stent thrombosis = angiographically documented stent occlusion with Thrombolysis in Myocardial Infarction (TIMI) flow grade 0 occurring within 24 h of stent implantation. Subacute stent thrombosis = stent occlusion or the finding of TIMI flow grade I or II associated with an intralumen filling defect occurring >24 h after stent implantation. Emergency PTCA = any percutaneous intervention performed for ongoing ischemia after the stenting procedure and with flow impairment at the stent site. Repeat PTCA = a new percutaneous intervention performed for the treatment of stent restenosis or of a new lesion. Vascular complications = the occurrence of bleeding or hematoma formation at the puncture site associated with the need for transfusion, vascular repair or prolonged external compression after initial successful sheath removal. Events were classified as occurring during the stenting procedure, during the hospital stay or during the follow-up period.
Procedural success = primary stent success without the need for emergency CABG or emergency PTCA and without the occurrence of Q wave myocardial infarction or death. Stent restenosis = ≥50% lumen reduction occurring at the stent site or immediately proximally or distally and demonstrated at follow-up angiography.
Follow-up. At the time of initial stent implantation, patients were informed about the need for angiographic and clinical follow-up. Before discharge, repeat angiography was scheduled for each patient 5 to 6 months after stent implantation. If follow-up angiography was performed at another institution the angiograms were obtained to permit performance of quantitative angiographic analysis. If symptoms recurred before the scheduled follow-up study, an angiogram was obtained earlier and was considered a follow-up angiogram if it showed restenosis or was performed >3 months after stent implantation. Clinical follow-up was performed by direct telephone interview with the patients. Follow-up information was collected on dedicated forms. For patients who had a clinical event such as elective CABG, myocardial infarction or death, clinical follow-up ended at the time of the event. If at the time of interview multiple events had occurred, all of them were recorded and the first event was considered for survival analysis. Follow-up was continued in patients who underwent repeat angioplasty for treatment of stent restenosis.
Statistics. Values with normal distribution are expressed as mean value ± SD. Data that are not normally distributed are expressed as median and range of values. A two-tailed Student t test and analyses of single and multiple variance were performed to test differences among continuous variables. The chi-square test was used to test categoric variables. Predictors of restenosis were evaluated by univariate and multivariate regression analyses. The Kaplan-Meier method was used to generate total survival and event-free survival curves. Differences were considered statistically significant at p < 0.05.
Patient and angiographic characteristics. There were 128 consecutive patients with a mean age of 56 ± 10 years; 91% were male. The complete clinical characteristics are presented in Table 1. A total of 139 lesions were treated. One previous PTCA had been performed in 124 patients (97%) and two previous PTCAs in 4. The mean time from the last PTCA to the occurrence of restenosis was 175 ± 154 days. The angiographic distribution and characteristics of the lesions treated are shown in Table 2. A total of 205 stents were implanted; 187 were Palmaz-Schatz stents. Other types of stent were occasionally used in anatomic settings considered unfavorable for the Palmaz-Schatz stent. The short Palmaz-Schatz stent was mainly used to treat a residual lesion not completely covered by a Palmaz-Schatz stent or to treat lesions in patients with unfavorable anatomy when other types of stents were not yet available. Details of the stents implanted are shown in Table 3. Multiple stenting was performed in 48 lesions (34%).
Procedural success. Primary stent success was achieved in 126 patients (98%). The success rate in the initial 83 patients who underwent stent implantation without IVUS guidance did not differ from that in the subsequent 42 patients undergoing stent implantation with IVUS guidance. The patients with primary stent success in the group undergoing stent implantation without IVUS guidance were treated with standard post-stenting heparin and oral anticoagulation for 1 month. Patients undergoing successful IVUS-guided stent implantation were treated with antiplatelet agents alone.
Complications. Complications occurred in four patients (3.1%). One patient died after undergoing successful stent implantation on an ostial lesion of the right coronary artery and sustaining cardiac tamponade due to right ventricular perforation from a temporary pacemaker wire. Uncomplicated emergency CABG was performed in two patients: in one because coronary rupture occurred during stent optimization and in one because a suboptimal post-stenting angiographic result did not appear suitable for improvement with current transcatheter techniques. The patient with coronary rupture had undergone stent dilation with a balloon/artery ratio of 1.2 and use of a semicompliant balloon inflated at 12 atm. The increase in balloon size after the increase in inflation pressure most probably changed the balloon/artery ratio unfavorably. One patient in the IVUS group had subacute stent thrombosis on day 14 after stent implantation. This patient was successfully treated with emergency angioplasty and remained symptom-free at 14 months with good results on angiographic follow-up.
Angiographic and intravascular ultrasound analysis. The quantitative angiographic data are shown in Table 4Table 5. The data in Table 5 show the results obtained before and after the utilization of IVUS. The significant difference in the final balloon pressure in the IVUS-guided group reflects the typical strategy of high pressure final dilation specifically employed with this approach. The IVUS variables of the 50 lesions undergoing IVUS-guided stent implantation are shown in Table 5. These patients satisfied the criteria for IVUS-guided optimal stent expansion previously reported [12, 13].
Angiographic restenosis and clinical follow-up. Angiographic follow-up was obtained a mean of 6.6 ± 3 months after the procedure in 110 (89%) of the 124 patients with successful stenting. The mean MLD at follow-up for all lesions of 2.14 ± 0.97 mm corresponded to a loss index of 0.30 ± 0.46. Angiographic restenosis based on 50% lumen diameter narrowing was found in 27 (25%) of 110 patients. The restenosis was found in a control angiogram obtained at 198 ± 135 days after the procedure, and the mean percent stenosis was 73 ± 12%. Of these 27 patients with angiographic restenosis, 23 underwent a new revascularization because of symptoms or documented ischemia (15 new angioplasties and 8 new CABG operations); the other patients continued on medical therapy owing to absence of demonstrable ischemia.
Clinical follow-up was available in all 125 patients with successful stenting at a mean of 21 ± 10 months (range 4 to 51). Late events occurred in 23 patients (19%) and included 15 coronary angioplasties, 8 elective CABG operations and 2 late deaths. No patient had a myocardial infarction at follow-up. The Kaplan-Meier actuarial survival curves for each cardiac event and for all events are shown in Fig. 1. The actuarial survival at 1 and 3 years was 98% and the event-free survival rate was 95% at 1 year and subsequently declined to 76%. In the 15 patients who had repeat angioplasty to treat stent restenosis clinical follow-up findings at 18 ± 5 months indicated that all 15 remained asymptomatic with no further events except in 2 patients who underwent CABG for disease progression. The final asymptomatic status including patients who underwent repeat angioplasty for stent restenosis was achieved in 106 patients (87%).
Anticoagulant regimens. Of the 128 study patients, 42 who underwent stenting later in the trial were treated only with antiplatelets agents (ticlopidine and aspirin). These patients treated without subsequent anticoagulation were part of an ongoing study intended to evaluate IVUS-guided stent implantation. The patients who underwent conventionally performed stent implantation and those who had IVUS-guided stent implantation are compared in Table 5. The only differences (both expected) between these two groups of patients were the length of hospital stay and the duration of follow-up interval.
Predictors of subsequent restenosis. No specific clinical feature or procedural aspect was found to predict angiographic restenosis (Table 6). No statistically significant difference was found in the incidence of restenosis regarding artery location (left anterior descending coronary artery 18%, right coronary artery 37%, left circumflex coronary artery 13% [p = NS]); lesion site (proximal 26%, mid 18%, distal 27% [p = NS]) and AHA/ACC lesion type (A 11%, B1 15%; B2 19%, C 38% [p = NS]).
The major finding of this study is that coronary stent implantation to treat restenosis after PTCA is associated with an angiographic second restenosis rate of 25% and very favorable long-term follow-up findings. This rate is lower than those reported for other transcatheter methods (directional atherectomy, rotational atherectomy or laser) used to treat restenotic lesions after PTCA [1–7, 14–16].
The influence of stenting technique. One unique feature of this study is that it analyzes two patient subgroups treated with different procedural methods. The first 83 patients underwent stenting without routine high pressure final stent dilation, without IVUS guidance and with subsequent anticoagulation; the subsequent 42 patients were treated only with antiplatelet agents and underwent stenting with both high pressure final stent dilation and IVUS guidance. The initial 83 patients, despite less aggressive dilation after stenting, underwent a rigorous angiographic optimization strategy utilizing an average final balloon size of 3.59 ± 0.55 mm, with a 1.1 ± 0.14 balloon/angiographic reference vessel ratio and with achievement of a final residual stenosis of 5.3 ± 10.85%. The data show that the major advantage of the implantation strategy in the subsequent 41 patients was a reduction in hospital stay. It follows that the major benefits of an aggressive post-stenting dilation strategy are probably the results of eliminating anti-coagulant agents, shortening the hospital stay and decreasing stent thrombosis by comparison with a standard technique with subsequent systemic anticoagulant previously reported by Savage et al. . In the latter study a subacute thrombosis rate of 4.7% and a restenosis rate of 39% were found in patients with previous angioplasty. Another report , using Wiktor stent implantation to treat restenotic lesions after PTCA, found a stent thrombosis rate of 15% and a restenosis rate of 30%. These findings may reflect the shortcomings of the traditional technique previously used to perform coronary stenting. However, two high volume single centers [19, 20] reported very low thrombosis rates and low restenosis rates with use of a standard stent placement approach without routine high pressure final stent dilation and with subsequent systemic anticoagulation. In our study, the occurrence of vessel rupture in one patient indicates the need to pay attention to the balloon/artery ratio, especially when utilizing compliant or semicompliant balloons.
Role of IVUS. Because only 41 patients in our study were treated with IVUS-guided stenting, we cannot draw firm conclusions on the role of IVUS in the results achieved in this small group. Multivariate analysis did not provide specific information concerning the role of clinical or procedural variables in subsequent stent restenosis. One reason may be the small group size; however, it is possible that stent restenosis was mainly controlled by factors not analyzed in this study in which an optimal result was achieved in most patients. In particular, the lack of association between the final MLD achieved and the risk of subsequent restenosis seems unexpected. A possible explanation for this negative finding is that the technique used produced the best possible final MLD in most lesions.
Although our study did not attempt to compare stenting versus angioplasty in the treatment of restenosis, some historical “control” groups may be analyzed. In the study of Williams et al.  in patients in the National Heart, Lung, and Blood Institute PTCA registry, the restenosis rate after a second PTCA was 34%. Another study from Emory University of 1,490 patients who underwent PTCA for restenosis showed angiographic restenosis in 51% of lesions . A recent review article of Levine at al.  combining data from eight publications reported a restenosis rate of 40% after angioplasty performed for a third or fourth restenosis.
From the clinical point of view it is positive that the 15 patients in our study who had stent restenosis and who underwent subsequent PTCA have been free of clinical recurrence at a mean follow-up interval of 8 months. It is also interesting that six patients who met the criteria for angiographic restenosis were free of inducible ischemia, did not require invasive treatment and had an uneventful follow-up. These findings support the conclusion that 60% to 70% angiographic stent narrowing is frequently not clinically relevant .
Conclusions. Considering these findings, we believe that coronary stenting can be safely used to treat restenosis after PTCA. The angiographic restenosis rate of 25% and the short hospital stay associated with a better implantation technique are likely to make stenting a cost-effective procedure for this specific indication . The role of IVUS in the group treated with final high pressure inflation and no anticoagulation was not specifically examined. However, it is likely that routine high pressure stent implantation associated with angiographic optimization will yield comparable results.
Limitations of the study. This retrospective observational study provides long-term follow-up results from a single center. The study was not designed to compare stenting for restenosis with other treatment modalities. The results of ongoing randomized studies such as the REST trial  may further support some of the preliminary findings of our observational work.
A.1 Abbreviations and Acronyms
AHA/ACC = American Heart Association/American College of Cardiology
CABG = coronary artery bypass graft surgery
IVUS = intravascular ultrasound
MLD = minimal lumen diameter
PTCA = percutaneous transluminal coronary angioplasty
TIMI = Thrombolysis in Myocardial Infarction
- Received February 7, 1996.
- Revision received April 18, 1996.
- Accepted May 24, 1996.
- THE AMERICAN COLLEGE OF CARDIOLOGY
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