Six-Month Angiographic Outcome After Successful Repeat Percutaneous Intervention for In-Stent Restenosis
Background—In-stent restenosis is an increasing clinical problem. Discordant results have been published regarding the risk of recurrent restenosis after repeat angioplasty for the treatment of in-stent restenosis.
Methods and Results—One hundred three consecutive patients (107 vessels) underwent repeat percutaneous intervention for the treatment of in-stent restenosis and were entered in a prospective angiographic follow-up program. Repeat balloon angioplasty was performed at 93 lesions (87%) and additional stenting at 14 lesions (13%). The primary success rate was 98%. Six-month angiographic follow-up was performed in 85% of eligible patients. Restenosis was determined by quantitative angiography. Restenosis defined as a >50% diameter stenosis at follow-up was observed at 22% of lesions. The rate of target-lesion revascularization at 6 months was 17%. Repeat intervention for diffuse in-stent restenosis and severe stenosis before repeat intervention were associated with significantly higher rates of recurrent restenosis.
Conclusions—The overall restenosis rate after repeat intervention for in-stent restenosis is low. The subgroup of patients with diffuse and/or severe in-stent restenosis, however, is at higher risk of recurrent restenosis and may benefit from alternative therapeutic strategies.
Recent studies1 2 have shown that coronary stenting (CS) reduces restenosis compared with balloon angioplasty; however, in-stent restenosis may occur in 20% to 30% of cases. Because of the extension of CS indications, the problem of the treatment of in-stent restenosis has assumed increasing importance. Although satisfactory short-term results have been reported with repeat balloon angioplasty, controversy still exists regarding the recurrent restenosis rate.3 4 5 6 7 The present study describes the 6-month angiographic outcome, assessed with quantitative angiography, of 103 consecutive patients who underwent repeat percutaneous intervention for the treatment of in-stent restenosis.
As part of a systematic follow-up program to detect restenosis 6 months after successful CS, 647 consecutive patients underwent coronary angiography between August 1994 and April 1997 in our institution. One hundred sixty-two patients (25%) had restenosis by quantitative coronary angiography (>50% diameter stenosis). Of these 162 patients with stent restenosis, 51 (31%) were treated medically, 8 (5%) underwent bypass surgery, and 103 (64%) underwent a repeat percutaneous intervention; these latter 103 patients form our study population.
Primary success (<50% residual stenosis with no major complication, ie, myocardial infarction, bypass surgery during hospitalization, or in-hospital death) was obtained in 101 (98%) of the patients. Before hospital discharge, all patients were prospectively asked to undergo systematic 6-month angiographic follow-up to detect recurrent restenosis. Two patients died during the follow-up period. Angiographic follow-up was obtained in 84 (85%) of the eligible patients at a mean (±SD) of 6.3±2.1 months after the procedure. The 15 remaining patients were contacted by telephone at 6 months; all were asymptomatic and refused angiographic follow-up.
Stenting and Repeat Angioplasty
CS was performed as previously described.8 High inflation pressures were used for final in-stent dilatation. The antithrombotic regimen comprised ticlopidine (250 mg twice daily for 6 weeks) and aspirin (160 to 300 mg daily indefinitely). Repeat balloon angioplasty was performed by use of standard techniques. Additional stents were implanted in a minority of cases (13%); other techniques such as rotablator or laser were not used in this series. The same antithrombotic regimen (ticlopidine and aspirin) was given for 6 weeks after repeat angioplasty.
Qualitative analyses were performed independently by two experienced interventional cardiologists. Disagreements were resolved by a further joint reading. The location of the restenotic lesions with respect to the stented segment was classified as being within the stent body or at the proximal or distal margin of the stent. Stenosis within the stent or at the margins was further classified as being either diffuse (>50% lumen narrowing >10 mm in length) or focal.
Quantitative computer-assisted angiographic measurements were performed in matched projections with use of the CMS system.9 Patients received intracoronary isosorbide dinitrate to achieve maximal vasodilation.
Data are presented as mean±SD. Comparisons between groups for continuous data were made with unpaired Student’s t tests. Differences between proportions were assessed by χ2 analysis.
Patient and lesion characteristics at the time of the initial stenting procedure and at the time of the repeat procedure are shown in Table 1⇓. Most of the patients had high-pressure implantation of either Palmaz-Schatz or Wiktor stents. The repeat procedure was most frequently performed for recurrent unstable (23%) or stable (48%) angina despite antianginal treatment; 17% of patients were asymptomatic on antianginal treatment but had evidence of ischemia during noninvasive testing; 12% of patients were asymptomatic on antianginal treatment, could not perform a maximal exercise test, and underwent repeat revascularization based on the decision of the cardiologist who performed the angiography. The repeat procedure was balloon angioplasty in the majority (87%) of cases and “in-stent stenting” in the remaining cases (13%). In-stent restenosis was most often focal (71%) and located within the body of the stent (80%). The proportion of focal (versus diffuse) restenosis (68%) was similar in the 59 patients who did not undergo repeat revascularization.
The quantitative angiographic measurements in the 87 lesions with angiographic follow-up are shown in Table 2⇓. Recurrent restenosis (>50% diameter stenosis by quantitative angiography) was observed at 19 lesions (22%). The rate of target-lesion revascularization at 6 months was 17%. As shown in Table 3⇓, repeat intervention for diffuse in-stent restenosis or severe stenosis before repeat intervention was associated with significantly higher rates of recurrent restenosis (rate of recurrent restenosis: diffuse=42%, focal=14%, P<.006; diameter stenosis >70% before repeat intervention=33%, diameter stenosis <70% before repeat intervention=11%, P<.02). The rate of recurrent restenosis was 23% when the repeat intervention was balloon angioplasty and 15% when it was repeat stenting (P=NS).
Our results demonstrate that repeat balloon angioplasty for the treatment of in-stent restenosis has a high immediate success rate and a favorable 6-month angiographic outcome.
As a consequence of the growing indications for CS, it is of critical importance to assess the efficacy of the potential treatment strategies for patients with in-stent restenosis. Previous studies3 4 5 have reported high angiographic restenosis rates after repeat balloon angioplasty for in-stent restenosis. This has prompted investigation of the possible use of nonballoon techniques (eg, rotational atherectomy, directional atherectomy, and laser) as an alternative to repeat balloon angioplasty.10 11 These studies reporting high recurrent restenosis rates, however, had low angiographic follow-up rates that may have led to an overestimation of the true angiographic restenosis rate. Indeed, this was pointed out by Baim et al.3 Discordant results were recently published by Reimers et al7 showing a very low rate of recurring clinical events in a series of 124 consecutive patients undergoing repeat angioplasty for in-stent restenosis; in that study, however, angiographic follow-up was not routinely performed and was obtained in only 19% of the patients.
In the present study, the angiographic follow-up rate was 85%. Moreover, the follow-up angiograms were analyzed by use of quantitative coronary angiography performed by independent observers. The overall 22% rate of angiographic restenosis is concordant with the good long-term clinical outcome reported by Reimers et al7 and supports the use of repeat balloon angioplasty as primary treatment for in-stent restenosis.
Although the overall angiographic outcome was good, repeat intervention for diffuse and severe in-stent restenosis was associated with a high rate of recurrent restenosis; the optimal treatment for these patients will need to be determined in randomized studies. Because the high propensity of these patients to develop recurrent restenosis may be related to residual plaque burden after repeat angioplasty, additional studies are needed to investigate the effect of debulking strategies in patients with diffuse restenosis.10 11 Another strategy may be repeat stent implantation. In the present study, the rate of recurrent restenosis after repeat stent implantation was low; the number of patients with repeat stent implantation is, however, too small to draw definite conclusions.
There are at least two limitations to the present study. First, despite the fact that to the best of our knowledge, this study is the largest study with systematic angiographic follow-up reported to date, the number of patients included was relatively modest, and larger studies will have to be designed to confirm our findings; this will be especially important for subgroup analyses. Second, this study was solely focused on the 6-month angiographic end point; however, our results are concordant with those of a study focused on long-term clinical outcome.7
In conclusion, stent restenosis is an increasing problem. In-stent balloon angioplasty appears to be a safe treatment strategy associated with low restenosis rates in focal lesions. Diffuse restenoses are at higher risk of recurrent restenosis and may benefit from alternative therapeutic approaches.
- Received November 3, 1997.
- Revision received December 3, 1997.
- Accepted December 4, 1997.
- Copyright © 1998 by American Heart Association
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