In patients with proximal left anterior descending (LAD) disease, percutaneous coronary intervention (PCI) is a valid alternative to coronary artery bypass grafting (CABG), offering similar long-term survival and relief of angina as CABG, though there is a greater need for new procedures.1,2 Coronary stenting provides clinical benefit in comparison with balloon angioplasty in patients with proximal LAD disease, and because of that, it is the most frequently employed PCI modality in these patients.3 However, the main limitation of coronary stents is in-stent restenosis (ISR) which may occur in ~20% of patients with a proximal LAD treated with bare metal stents.3,4 The LAD provides coronary blood supply to a large part of the myocardium,5 thus, patients with proximal LAD in-stent restenosis are frequently sent for CABG.6 The objective of this study was to evaluate the clinical long-term outcome of patients with proximal LAD ISR who were treated with a second PCI procedure. For this purpose, we followed up 123 patients with proximal LAD ISR who underwent a subsequent PCI procedure. Patients and Methods Study population. This was a single-center study in which patients were enrolled retrospectively from the Division of Interventional Cardiology’s database at our institution. From March 1996 to January 2002, 249 patients with proximal LAD ISR were identified at our center. In 139 of them (55.8%), a new revascularization procedure was planned due to the presence of symptoms or silent ischemia. This revascularization procedure was CABG in 16 patients. The study population is comprised of the remaining 123 patients with proximal LAD ISR in which a second PCI procedure was performed. Patients were followed up for a mean of 3.3 ± 2.8 years. Clinical follow-up was performed by clinical interview by telephone. Clinical endpoints were death, need for coronary artery bypass grafting, new target vessel revascularization procedures, and the combination of these events. Interventional procedure. Cardiac catheterization was performed via the femoral approach. All patients had significant (> 50%) ISR involving the proximal segment of the LAD. Intracoronary nitroglycerin 0.2 mg was administered before and after the cineangiograms. Quantitative coronary analysis was performed off-line using the CMS system (MEDIS, Medical Imaging Systems, Leiden, The Netherlands) with a contrast-filled catheter as a calibration reference. All patients had a > 50% stenosis within the stent and/or 10 mm in length, respectively). The following measurements were determined before and after PCI for ISR: reference vessel diameter, minimum lumen diameter, maximum stenosis percentage, and stenosis length. An angiographically successful result was defined as the presence of Thrombolysis In Myocardial Infarction (TIMI) flow grade 2 or 3 associated with Statistical analysis. Statistical analysis was performed using the SPSS 9.0 statistical package (Chicago, Illinois). Continuous variables were expressed as mean ± standard deviation, and discrete variables as proportions (percentages). Comparison of continuous variables between the two groups were studied by the Student’s t-test, and comparison of proportions by the Chi-square test. Cumulative freedom from events was expressed using the Kaplan-Meier cumulative survival curves, and comparison among groups was evaluated by the Log-Rank and Breslow tests. Associations were considered statistically significant when p Baseline characteristics. Baseline clinical characteristics are shown in Table 1. Time since stent implantation was 8.3 ± 10.2 months (range: 1.8–85.8). The mean age was 62 ± 12 years of age, 26.8% of patients were diabetics, and 45.5% had an acute coronary syndrome as clinical presentation of restenosis. ISR was diffuse in 36 patients (29.2%). Procedural data. The type of stent implanted in the initial procedure was: NIR® (Boston Scientific/SCIMED, Maple Grove, Minnesota) in 37 patients (30.1%), Palmaz-Schatz™ (Cordis Endovascular, J & J, Warren, New Jersey) in 18 (14.6%), MULTI-LINK™ (Guidant Corp., Indianapolis, Indiana) in 16 (13.0%), Bx VELOCITY™ (Cordis Corp., Miami, Florida) in 15 (12.2%), AVE (Medtronic AVE, Inc., Minneapolis, Minnesota) in 11 (8.9%), Wiktor (Medtronic Inc.) in 8 (6.5%), and other stents in 18 patients (14.6%). The diameter and length of the stent implanted at the initial procedure was 3.05 ± 0.44 mm and 20.09 ± 7.39 mm, respectively. The most frequent PCI modality for ISR was balloon alone (n = 67, 54.5%). A new coronary stent was implanted in 40 patients (32.5%) due to at least one of the following reasons: coronary dissection after in-stent balloon angioplasty, significant stenosis outside of the stent, or inclusion in the RIBS (Restenosis Intrastent: Balloon angioplasty versus elective Stenting) trial, that randomized patients with ISR to balloon angioplasty or stent.7 An additional device was used in the remaining 16 patients (13.0%) (intracoronary brachytherapy [n = 8; 6.5%], laser [n = 7; 5.7%], and rotational atherectomy [n = 1; 0.8%]). Table 2 shows immediate angiographic data on the quantitative coronary analysis. Angiographic results were successful in 121 patients (98.4%). In 2 patients, PCI was not successful, with 1 patient ultimately undergoing CABG, and another patient maintained on medical therapy. Long-term follow-up. Of the 123 patients, 121 (98.4%) were followed up for 3.3 ± 2.8 years. The number of patients followed up at 1, 2, 3, 4, and 5 years was 96, 77, 58, 43, and 36, respectively. There were 7 deaths during follow-up. The cumulative survival rate was 98.3 ± 1.2% at 1 year, and 95.2 ± 2.5%, at 3 years (Figure 1). Nine patients underwent CABG: one patient with an unsuccessful angiographic result was sent for elective CABG during initial hospitalization; 6 patients with recurrent ISR were surgically revascularized; and 2 patients ultimately underwent surgery after having a third documented ISR. The cumulative probability of remaining CABG-free was 94.5 ± 2.2% at 1 year, and 93.3 ± 2.5% at 3 years. The cumulative probability of being alive and CABG-free was 92.8 ± 2.5% and 88.5 ± 3.4% at 1 and 3 years, respectively (Figure 1). Twenty-one patients required subsequent revascularization procedures: 12 PCI, 7 CABG, and 2 underwent PCI followed by CABG. The probability of being free from new revascularization procedures was 83.5 ± 3.4% and 81.5 ± 3.8% at 1 and 3 years, respectively. The probability of being alive and free from new revascularization procedures was 82.2 ± 3.6% and 76.9 ± 4.3% at 1 and 3 years, respectively (Figure 1). Figure 3 compares the long-term outcome of patients with focal and diffuse ISR. In 82 patients (66.7%), angiographic follow-up was performed at 9.5 ± 12.4 months (range: 1.7–74.1). In 30 patients (36.6% of those undergoing angiographic follow-up and 24.5% of the whole population), a second ISR was documented. Of those patients, 14 (46.7%) underwent a subsequent new PCI procedure, and 6 (20.0%) were sent for CABG, whereas the remaining 10 (33.3%) patients remained on medical therapy. Of the 14 patients who required subsequent PCI for a second ISR, 2 ultimately underwent CABG for a third ISR. Patients with proximal LAD ISR initially treated with CABG. During the study period, 16 patients with proximal LAD ISR initially underwent CABG. The decision to send the patient for CABG or a second PCI was primarily left to the discretion of the clinical cardiologists, but these patients had diffuse ISR more frequently (n = 9, 56.3%; p = 0.03, compared to patients who initially underwent a second PCI), and had a relatively high rate of disease in the left main and/or the origin of the left circumflex artery (n = 4, 25.0%). Baseline clinical characteristics showed no significant differences compared to patients initially treated by a second PCI, except for a lower frequency of acute coronary syndrome as a clinical presentation of ISR (Table 3). The diameter and length of the stent implanted in the initial procedure were 2.95 ± 7.39 mm and 20.63 ± 11.09 mm, respectively (p = NS, in comparison to patients initially treated with a subsequent PCI procedure). Among those 16 patients, 2 suffered events: 1 patient required reintervention during the post-operative period and ultimately died, and the other patient died during the post-operative period. The remaining 14 patients experienced no events during follow-up. For the patients who initially underwent CABG, the probability of being alive and free from a second CABG was 87.5 ± 8.3% at 1 and 3 years (Log-Rank: p = 0.888; Breslow: p = 0.569, compared to the patients who initially underwent a second PCI; Figure 3A). The probability of being alive and free from new revascularization procedures was also 87.5 ± 8.3% at 1 and 3 years (Log-Rank: p = 0.501; Breslow: p = 0.732, compared to patients initially treated percutaneously; Figure 3B). Discussion The LAD supplies coronary blood flow to a large part of the myocardium,5 hence, proximal LAD occlusion leads to a high mortality rate. For this reason, patients with proximal LAD disease were classically referred for CABG, especially those who had multi-vessel disease. In addition, proximal LAD disease carries a high risk of restenosis,8 though it has decreased from 40% to 20% with the use of bare metal stents.3 Thus, with the widespread use of coronary stents, PCI may be considered the first-choice strategy for patients with proximal LAD stenosis, even in those with multi-vessel disease. In the ERACI-II study, patients with multi-vessel disease and significant proximal LAD stenosis had similar long-term survival rates when treated with coronary stenting or CABG — though at the obvious cost of a higher rate of new revascularization procedures.9 Drenth and co-workers randomized 102 patients with single proximal LAD disease to coronary stenting or off-pump coronary surgery. Although there was a trend toward a higher rate of major adverse cardiac events in patients who received a stent, the mortality rate was even lower (though not significantly) than in patients who were treated surgically (0% vs. 3.9%).10 Similar results were obtained in the study by Diegeler and co-workers in which patients with proximal LAD disease had higher event rates than those treated with minimally invasive bypass surgery, though again, this was mainly due to a greater frequency of new revascularization procedures, with mortality rate being (though non significantly) lower in patients who received a stent (0% versus 2%).11 Despite the high rate of subsequent restenosis following percutaneous treatment of ISR, treating ISR with a new PCI procedure is associated with a very high success rate and a very low rate of peri-procedural complications. Apart from intracoronary brachytherapy, other modalities have not shown to improve the results obtained by balloon angioplasty alone,7,12–14 at least in the case of focal ISR.15,16 Intracoronary brachyteraphy17 is reserved for diffuse ISR and is available in a few centers, and the use of drug-eluting stents for the treatment of ISR is currently under evaluation.18 In cases of ISR involving the proximal LAD, cardiologists may be tempted to send the patient for CABG once a first PCI procedure has failed. We have shown that a new PCI procedure is feasible in most of these patients, with a good clinical outcome and a relatively low proportion of patients needing CABG in the long-term. Only 1.7% and 4.2% had died at 1 and 3 years, respectively, and only 10.7% required CABG at 5 years. These data support a subsequent interventional approach in most cases of proximal LAD ISR. In our study population, most patients underwent balloon angioplasty alone and/or stent implantation. Other modalities such as brachytherapy, laser, and rotational atherectomy, were used in only 13% of cases. We found no significant differences associated with the modality used. In one study, rotational atherectomy for proximal LAD ISR was associated with very good long-term clinical outcomes.19 Brachytheraphy has improved the outcome of patients with ISR, especially in diffuse ISR.17 In our study, this benefit may have been masked by the less frequent use of brachytherapy and the shorter follow-up periods for the patients treated with this modality, both due to the inclusion period of the study population. Study limitations. The main limitation of this study is that it was not a randomized comparison between a second PCI procedure and other strategy (e.g. CABG). Rather, our study population is a selection 123 patients among 249 with proximal LAD ISR. This study has, however, shown favorable long-term clinical outcomes for patients with proximal LAD ISR who undergo a subsequent PCI. The second limitation is that the drug-eluting stent era is now well on its way, and the outcomes of our study population would probably be even better had these types of stents been used. Conclusions and practical implications. In patients with in-stent restenosis involving the proximal segment of the left anterior descending coronary artery, a second percutaneous procedure is a feasible and safe long-term strategy, with few patients finally requiring coronary artery bypass grafting. Surgical revascularization, therefore, should not necessarily be indicated for these patients.
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