Elderly patients have a favorable outcome after intracoronary radiation for in-stent restenosis.

Intracoronary radiation therapy (IRT) reduces recurrent in-stent restenosis (ISR) by inhibition of smooth muscle cell proliferation. The ability of these cells to replicate is limited with age due to changes in the telomeres. The purpose of this study was to assess the effect of age on outcomes following IRT for ISR. We evaluated 1,088 patients with 6-month clinical follow-up who were enrolled in radiation trials for ISR using gamma- and beta-emitters. Patients were analyzed within and between IRT (n = 861) or placebo therapy (n = 227) in four age groups (< 55, 55-65, 66-75, > 75 years). Baseline characteristics were similar within each age group of IRT patients, except elderly patients (> 75 years) had a lower rate of diabetes (28% in patients > 75 years; P = 0.008) and a higher rate of previous CABG (59% in patients > 75 years; P < 0.001). The rate of target lesion revascularization (TLR) was reduced in the elderly. TLR at 6 months was 18% in patients < 55 years, 21% in 55-65 years, 12% in 66-75 years, and 10% in patients > 75 (P = 0.009). The MACE rate at 6 months was 21% in patients < 55 years, 29% in 55-65 years, 26% in 66-75 years, and 17% in patients > 75 (P = 0.03). No effect of age was seen in placebo patients. IRT-treated patients had reduced MACE compared to placebo in all age groups, driven by reduced target vessel revascularization. Age was an independent predictor of MACE at 6 months (OR = 0.8; CI = 0.70-0.93; P = 0.004). Angiographic restenosis was not clearly associated with need for TLR in patients > 75 years. In elderly patients (> 75 years) treated with IRT for ISR, the rate of TLR was significantly reduced compared to younger patients. However, this reduction in TLR was not associated with a reduction in angiographic restenosis, suggesting that TLR should not be used as a surrogate for angiographic evaluation.     

Repeated intracoronary beta radiation for recurrent in-stent restenosis.

More than 70% of percutaneous coronary interventions are followed by a stent implantation. In-stent restenosis still occurs in 20-30% of patients and remains a therapeutic challenge. At present only vascular brachytherapy has been shown to be an effective treatment option. We report here one case of recurrent in-stent restenosis after vascular brachytherapy that was successfully treated by a second beta radiation treatment.     

Three-year follow-up after intracoronary beta-radiation therapy for in-stent restenosis.

BACKGROUND: Most studies that proved intracoronary radiation therapy (IRT) to be highly effective to reduce recurrent restenosis after treatment of in-stent restenosis (ISR) have looked at time periods up to 12 months. Whether the beneficial effect from radiation is sustained during long-term follow-up remains a concern. This study sought to evaluate the effectiveness of IRT using a beta-emitter during a 3-year follow-up period. METHODS: One hundred twenty-eight consecutive symptomatic patients (mean age, 63 +/- 11 years) with 134 in-stent restenotic lesions were treated for ISR with IRT (noncentred beta-emitter, Novoste; radiation dosis 21.1 +/- 3.1 Gy). Six-month angiographic follow-up was obtained in 104 patients (81%) with 105 lesions (78%). All patients underwent 36-month clinical follow-up. RESULTS: Six-month angiographic restenosis rate was 22% in stent (29% in lesion) with an in-stent late loss of 0.49 +/- 0.62 mm. Target lesion resvascularization (TLR) at 6-month follow-up was performed in 23 cases (18%). MACE (death, myocardial infarction, and target vessel revascularisation) was observed in 24 patients (19%). At 36-month follow-up, TLR increased to 36 cases (28%) and MACE was observed in 47 patients (37%). In a multivariate analysis, minimal lumen diameter before treatment of ISR using IRT was the only predictor of recurrent TLR at 36 months (OR = 0.131; 95% CI, 0.068-0.254; p = 0.002). In a subgroup of patients (N = 15) without restenosis at 6-month angiography but with clinically driven recurrent late angiography (mean, 18 +/- 7 months); in-lesion late loss increased from 0.47 +/- 0.54 mm at 6 months to 1.27 +/- 0.76 mm at repeated angiography (p = 0.005). CONCLUSION: There is a considerable number of delayed recurrent restenosis post IRT for ISR. This is due to ongoing late loss more than 6-month post IRT. The minimal lumen diameter before IRT predicts the need for recurrent TLR at 36 months.     

Impact of intracoronary radiation on in-stent restenosis involving ostial lesions.

The aim of this study was to compare 6-month clinical outcomes of patients with in-stent restenosis (ISR) involving the ostium treated with intracoronary radiation therapy (IRT) compared to placebo therapy, and also to nonostial lesions treated with IRT. Coronary interventions in ostial lesions have a high rate of recurrence of restenosis. The impact of IRT on ostial ISR has been inadequately characterized. We assessed patients enrolled in gamma (192-iridium) and beta (90-yttrium, 32-phosphorus) radiation trials for ISR at the Washington Hospital Center. Of patients receiving IRT, 105 (8%) patients had ostial ISR and 1,289 (92%) patients had nonostial ISR. Twenty-seven patients had ostial ISR and received placebo therapy. Baseline demographic and angiographic and procedural details were similar, except ostial IRT patients had a trend toward shorter lesions (15.4 +/- 10.8 vs. 24.1 +/- 12.2 mm; P < 0.001) and had a higher rate of saphenous vein graft disease (46% vs. 19%; P < 0.001) compared to nonostial IRT patients. At 6 months, ostial lesions treated with IRT for ISR had a reduced rate of target lesion revascularization (TLR) compared to ostial lesions treated with placebo (15% vs. 43%; P = 0.004). Outcomes at 6 months were similar for the ostial and nonostial IRT groups including TLR (15% vs. 14%; P = 0.80) and composite major adverse cardiac events (18% vs. 15%; P = 0.46). Intracoronary radiation therapy is effective for ostial in-stent restenotic lesions and should be comfortably used for this challenging anatomic location.     

Intracoronary radiation therapy for multi-drug resistant in-stent restenosis: initial clinical experience.

While randomized clinical trials have demonstrated the excellent efficacy of sirolimus-eluting stents (SES) for de novo lesions, the optimal treatment for SES-restenosis is not known. Management may include stand-alone balloon angioplasty, repeat SES implantation, or placement of a drug-eluting stent (DES) with an alternative antiproliferative agent (i.e., a paclitaxel-eluting stent, PES). The appropriate management strategy for recurrent restenosis after PES implantation for SES restenosis is even less clear. We report the initial clinical experience with intracoronary radiation therapy (ICRT) for multi-DES resistant restenosis. We performed ICRT in five patients with recurrent restenosis after treatment with both SES and PES. Over a median follow-up of 256 days (range 75-489 days), one patient had a target lesion revascularization at 182 days and subsequently died at 483 days following the procedure. Our findings support the further study of this management approach.     

Real-world clinical practice of intracoronary radiation therapy as compared to investigational trials.

Intracoronary radiation therapy (IRT) is well established in clinical practice as an effective treatment for in-stent restenosis. We aimed to determine if the 6-month clinical outcome of patients treated postapproval for marketing [commercial radiation (CR)] is equivalent to those patients enrolled in the Washington Radiation for In-Stent Restenosis Trials [Gamma WRIST and Beta WRIST; investigational radiation (IR)]. The 6-month clinical outcome of 110 consecutive patients with 125 lesions who received IRT (gamma, (192)Ir, 15-18 Gy, n = 6; or beta, (32)P, 20 Gy, n = 20; or (90)Sr/Y, 18.4-23.0 Gy, n = 99) in CR was compared with the 6-month clinical outcome of 117 patients with 117 lesions who received IRT ((192)Ir, 15 Gy, n = 65, in Gamma WRIST; and (90)Y, 20.6 Gy, n = 52, in Beta WRIST) in IR. Patients in CR were treated with wider radiation margins. The CR received antiplatelet therapy for at least 6 months and the IR for 1 month. The baseline characteristics of both groups were similar. Use of atheroablation devices was less in CR than IR (15.2% vs. 32.8%, respectively; P = 0.001). The overall major adverse cardiac events (death, Q-wave myocardial infarction, and target vessel revascularization; 18.2% vs. 29.1% in IR; P = 0.05) were significantly lower in the CR when compared with patients in the IR. The real-world clinical practice of IRT demonstrates lower events and better clinical outcomes. This is most likely a result of implementation of the lessons learned from the clinical trials such as optimizing the dosimetry by using a higher dose, treating wider margins to minimize edge effect, and administering prolonged antiplatelet therapy to abolish late thrombosis.     

Long-term follow-up of brachytherapy for treatment of allograft in-stent restenosis.

The experience of brachytherapy in the treatment of in-stent restenosis of allograft arteries is limited. We present two cases of in-stent restenosis treated with brachytherapy with favorable angiographic follow-up at 10 months in one patient and at 17 months in the other.     

Balloon-based radiation therapy for treatment of in-stent restenosis in human coronary arteries: results from the BRITE I study.

Catheter-based intracoronary radiation therapy demonstrated reduction of the recurrence rate of in-stent restenosis by 35%-50% when compared to conventional therapy. The objectives of this study were to determine the safety and feasibility of a new balloon-shaped source design and a higher applied dose to reduce the restenosis rates. Thirty-two patients with in-stent restenosis who met study eligibility criteria were successfully treated with standard PCI techniques. Following a successful intervention, a P-32 beta-balloon source was positioned to cover the angioplasty site and a dose of a 20 Gy at 1 mm from the surface of the source was administered. The primary endpoint was a composite of major adverse cardiac events (any death, MI, emergent CABG, or repeat target vessel revascularization) during 6 months of follow-up. At 6 months, only one patient underwent repeat PTCA to the target vessel (3%). There were no instances of death, emergency surgery, late thrombosis, total occlusions, or MI. Binary restenosis measured by QCA at the stented segment was 0% and for the whole analysis vessel was 7.5%. Beta-radiation delivered with a balloon P-32 source design for patients with in-stent restenosis results in lower than expected rate of angiographic and clinical restenosis and the absence of late complications.     

Relationship between neointimal regrowth and mechanism of acute lumen gain during the treatment of in-stent restenosis with or without supplementary intravascular radiation.

We investigated whether neointimal regrowth is related to the mechanism of acute lumen gain during the treatment of in-stent restenosis (ISR) lesions both with and without adjunct intravascular brachytherapy. From the WRIST (Washington Radiation for In-Stent Restenosis Trial) cohort, 54 ISR patients ((192)Ir, 29; placebo, 25) were treated with nonrepeat stenting percutaneous interventions (excimer laser, rotational atherectomy, and/or balloon angioplasty) prior to (192)Ir or placebo therapy. Using Simpson's method, serial volumetric intravascular ultrasound (IVUS) analyses (pre- and posttreatment and 6-month follow-up) were analyzed to obtain stent, lumen, and intimal hyperplasia (IH) volumes that were then adjusted for stent length to create stent, lumen, and IH volume indexes. In the placebo group, the acute reduction of neointima (1.6 +/- 1.4 mm(3)/mm) was counteracted by intimal regrowth (2.1 +/- 1.7 mm(3)/mm). The amount of intimal regrowth correlated directly with the intimal reduction due to the intervention (r = 0.76; P < 0.001), but not with the amount of additional stent expansion. In the (192)Ir-treated group, intimal regrowth was significantly less than in the placebo group (-0.3 +/- 0.1 vs. 2.1 +/- 1.7 mm(3)/mm; P < 0.001) despite a similar initial intimal reduction (1.3 +/- 0.9 vs. 1.6 +/- 1.4 mm(3)/mm; P = NS). No correlation was found between intimal reduction at the time of the procedure and intimal regrowth in the (192)Ir group. In this study, neointimal regrowth following treatment of ISR lesions correlates directly with the extent of acute intimal volume reduction, but not with the extent of additional stent expansion. This relation is not seen in ISR segments treated with radiation, where intimal regrowth is substantially inhibited.     

Combined cutting balloon angioplasty and intracoronary beta radiation for treatment of in-stent restenosis: clinical outcomes and effect of pullback radiation for long lesions.

Intracoronary beta (beta) radiation decreases the incidence of target lesion revascularization after percutaneous intervention (PCI) for in-stent restenosis (ISR). Cutting balloon (CB) angioplasty may also be superior to other percutaneous techniques for the treatment of ISR. We sought to study the outcomes of patients with ISR who underwent both CB angioplasty and intracoronay beta radiation and compare them to patients with ISR who underwent other PCI techniques without concomitant radiation. We also sought to evaluate the safety and efficacy of pullback intracoronary beta radiation for the treatment of long ISR lesions. Between January 2001 and November 2001, 102 patients (mean age = 55 +/- 13 years) with ISR underwent both CB angioplasty and intracoronay beta radiation. beta radiation was delivered using the Beta Cath (Novoste) 30 mm system, and pullback radiation was performed in 41 patients. A comparison group included a total of 393 patients with ISR who underwent other PCI techniques without concomitant intracoronary radiation therapy. Follow-up was obtained in 99 patients (97%) in the CB angioplasty with intracoronary radiation group and 377 patients (96%) in the comparison group. At follow-up, both target vessel revascularization (TVR) and major adverse cardiovascular events (MACE) occurred significantly less in the CB angioplasty with intracoronary radiation group than in the comparison group (7% vs. 18% for TVR, and 14% vs. 24% for MACE; P < 0.05 for both). In the pullback radiation group, TVR was performed in five patients (12%), and MACE occurred in eight patients (20%). A combination of CB angioplasty and intracoronay beta radiation for ISR seems to yield low rates of subsequent target vessel revascularization and adverse cardiac events. In addition, pullback beta radiation using the Beta Cath (Novoste) 30 mm system is safe and can be used to treat long ISR lesions effectively. Further randomized trials are needed to confirm these findings.     

Long-term clinical and angiographic outcome of patients with occlusive in-stent restenosis treated with (32P) beta-brachytherapy.

The objective of this study was to determine the safety and efficacy of (32)P beta-brachytherapy in totally occlusive in-stent restenosis (ISR). Patients with occlusive ISR were generally excluded from the randomized clinical trials on intracoronary brachytherapy (utilizing either gamma- or beta-sources) that have shown reductions in restenosis rate and need for revascularization procedures. We analyzed short- and long-term effects of (32)P beta-brachytherapy (20 Gy) in 27 patients (28 lesions) with occlusive ISR and 84 (99 lesions) patients with nonocclusive high-risk ISR. The primary outcome measure was frequency of in-lesion angiographic binary restenosis at 7 months. Secondary endpoints were rates of major adverse cardiac events (MACE), target vessel revascularization (TVR), clinically driven TVR, and target lesion revascularization (TLR). (32)P beta-brachytherapy was feasible and safe and provided similar postprocedural angiographic results in the two clinically comparable groups. However, the 7-month binary restenosis rate was higher in the occlusive group, as were the MACE and late total occlusion rates. Multivariate logistic analysis of the overall population indicated occlusive pattern to be the only independent predictor of angiographic restenosis. In both groups, recurrent lesions most often showed a focal pattern with significant reduction of length. Although safe and effective in high-risk ISR, (32)P brachytherapy at 20 Gy does not appear to be sufficient to avoid long-term restenosis in patients with occlusive lesions. Further studies should determine the most suitable source and dosage of brachytherapy for patients with occlusive ISR.     

Long-term angiographic follow-up after successful repeat balloon angioplasty for in-stent restenosis

BACKGROUND: Coronary stent implantation is associated with improved angiographic short-term and mid-term clinical outcome. However, restenosis rate still remains between 20 and 30%. HYPOTHESIS: The purpose of the study, performed as a prospective angiographic follow-up to detect restenosis, was to evaluate the immediate and the 6-month angiographic results of repeat balloon angioplasty for in-stent restenosis. METHODS: From April 1996 to September 1997, 335 stenting procedures performed in 327 patients underwent prospectively 6-month control angiography. Of the 96 lesions that showed in-stent restenosis (> 50% diameter stenosis) (29%), 72 underwent balloon angioplasty. RESULTS: The primary success rate was 100%. Follow-up angiogram at a mean of 6.9 +/- 2.4 months was obtained in 54 patients. Recurrent restenosis was observed in 24 of the 55 stents (44%). Repeat intervention for diffuse and body location in-stent restenosis before repeat intervention was associated with significantly higher rates of recurrent restenosis (p < 0.001 and p < 0.05, respectively). Of the 19 patients who underwent further balloon angioplasty (100% success rate), coronary angiography was performed in 18 (95%) at a mean of 8.2 +/- 2.0 months and showed recurrent restenosis in 12 patients (67%). Further repeat intervention for diffuse and severe in-stent restenosis before the second repeat intervention was associated with significantly higher rates of further recurrent restenosis (p < 0.05 and p < 0.005, respectively). CONCLUSIONS: Although balloon angioplasty can be safely, successfully, and repeatedly performed after stent restenosis, it carries a progressively high recurrence of angiographic restenosis rate during repeat 6-month follow-ups. The subgroup of patients with diffuse, severe, and/or body location in-stent restenosis proved to be at higher risk of recurrent restenosis.     

介入治疗后有或无冠脉内放射治疗对老年支架内再狭窄的作用和疗效:血管内超声分析

目的　采用血管内超声 (IVUS)评价常规介入治疗术 (CIT)有或无联合冠脉内放射治疗 (IRT)对支架内再狭窄 (ISR)复发的作用及随访观察 1年的临床疗效。方法　 99例ISR的患者经常规介入治疗后随机分为CIT IRT组和CIT组 ,在放疗后即刻和 6个月行IVUS检查 ,分别测量支架、管腔及增生内膜 (IH)面积 ,经计算得到支架、管腔内和IH体积并临床随访 1年。结果　两组基线指标无显著性差异 ,具有可比性。术后 6个月 ,CIT IRT组和CIT组的最小管腔面积 (MLA)各为 (4.30± 2 .0 0 )mm2 与 (2 .81± 2 .56)mm2 (P =0 .0 0 6) ,随访 6个月与放射治疗后即刻MLA差值各为 (- 0 .55± 1 .35)mm2 与 (- 1 .93± 1 .66)mm2 (P <0 .0 0 1 )。CIT IRT组和CIT组的IH体积各为 (69.2 3± 58.57)mm3 与 (1 1 6 .91± 1 2 1 .83)mm3 (P =0 .0 2 1 ) ,随访 6个月与放射治疗后即刻IH体积差值各为 (1 9.50± 35 .90 )mm3 与 (51 .36± 58.80 )mm3 (P =0 .0 1 7)。CIT IRT组 ,随访 6个月 ,MLA≥ 4mm2 的比例明显高于CIT组 (52 .7%与 2 4 .0 % )。术后 6个月 ,冠脉造影显示 ,CIT IRT组和CIT组ISR的复发率分别为 2 4 .53 %与 78.6 % (P =0 .0 2 7)。临床随访 1年 ,CIT IRT与CIT组的主要不利心脏事件 (MACE)、靶血管再次成形术 (TVR)及靶     

Angiographic and clinical outcomes at 8 months of cutting balloon angioplasty and beta-brachytherapy for native vessel in-stent restenosis (BETACUT): results from a stopped randomized controlled trial.

The objective of this study was to assess angiographic and clinical outcomes of cutting balloon (CB) angioplasty and concomitant Sr/Y-90 beta-brachytherapy as a treatment modality for patients with native vessel in-stent restenosis (ISR). Procedural advantages over the standard balloon (SB) have been claimed for the CB. Intracoronary brachytherapy preceded by SB angioplasty is regarded as the treatment of choice in patients with ISR. In an interim analysis of a prospective randomized trial designed for 652 patients, 100 consecutive patients with ISR were assigned to treatment with SB angioplasty (n = 51) or CB angioplasty (n = 49), followed in either case by Sr/Y-90 beta-brachytherapy. Quantitative coronary angiography at baseline, postintervention, and at 8 months was performed by an independent central laboratory. More than 90% of target lesions in the overall patient population were diffuse, with 14% of stents totally occluded. Procedural parameters and immediate angiographic outcomes were essentially the same in either study arm. At 8 months, no statistically significant differences were observed in recurrent angiographic restenosis (SB = 26.1%; CB = 29.5%; P = 0.82), target lesion revascularizations (SB = 13.7%; CB = 8.2%; P = 0.53), and major adverse cardiac events (SB = 15.7%; CB = 8.2%; P = 0.36). In this interim analysis, there was no indication of a beneficial effect of CB use over SB use in terms of angiographic or clinical outcomes at 8-month follow-up. CB angioplasty appears to be as safe and efficacious as SB angioplasty in beta-radiation treatment of patients with predominantly diffuse native vessel ISR. It was decided to discontinue the trial.     

Coronary stent strut avulsion in aorto-ostial in-stent restenosis: potential complication after cutting balloon angioplasty.

We report a case of stent strut avulsion by the cutting balloon during the withdrawal of the deflated balloon catheter in aorto-ostial in-stent restenosis, which was managed successfully by another stent. The proposed mechanisms and recommendations to avoid this rare complication are provided.     

Intravascular ultrasound analysis of beta radiation therapy for diffuse in-stent restenosis to inhibit intimal hyperplasia.

We evaluated the efficacy of beta-radiation therapy ((188)Re-MAG(3)) to inhibit intimal hyperplasia (IH) in diffuse in-stent restenosis by intravascular ultrasound (IVUS) analysis in 50 patients. Nine patients who did not agree with radiation therapy, and therefore underwent rotational atherectomy and balloon angioplasty for diffuse in-stent restenosis in the same study period, were selected for control groups. Serial IVUS comparisons were available in 44 of 50 patients with radiation therapy and 7 of 9 control patients. At 6-month follow-up, there was less significant increase of IH area in patients with radiation therapy than in control patients (Delta IH area = 0.1 +/- 0.8 mm(2) vs. 2.6 +/- 1.8 mm(2), P > 0.001 in mean values, and 0.6 +/- 1.4 mm(2) vs. 2.9 +/- 2.1 mm(2), P = 0.026 in values of follow-up lesion site, respectively). In conclusion, beta-radiation therapy might be an effective treatment modality to inhibit intimal hyperplasia in patients with diffuse in-stent restenosis.     

Three-year follow-up after intravascular gamma-radiation for in-stent restenosis in saphenous vein grafts.

The Washington Radiation for In-Stent Restenosis Trial in Saphenous Vein Grafts (SVG WRIST) demonstrated safety and efficacy of intravascular radiation therapy (IRT) for the treatment of in-stent restenosis (ISR) in SVG at 12 months. In this study, we aimed to examine whether the safety and efficacy of IRT is durable up to 36 months. One hundred twenty patients with diffuse ISR in SVG underwent balloon angioplasty, laser or atherectomy ablation, and/or additional stenting. After successful intervention, patients were randomly assigned in a double-blind fashion to intravascular treatment with a ribbon containing either iridium (Ir)-192 (n = 60) or nonradioactive seeds (n = 60). The prescribed dose at 2 mm from the source was either 14 or 15 Gy in vessels 2.5-4.0 mm or 18 Gy in vessels > 4.0 mm in diameter. At 36 months, target lesion revascularization (TLR; 43% vs. 66%; P = 0.02) and target lesion revascularization-major adverse cardiac event (TLR-MACE; 49% vs. 71%; P = 0.02) rates continued to be lower in the IRT group, but both target vessel revascularization (TVR; 59% vs. 71%; P = 0.17) and TVR-MACE (63% vs. 77%; P = 0.11) rates were not. In SVG WRIST, patients with ISR treated with IRT had a marked reduction in the need for repeat TLR at 36 months, with sustained clinical benefit at 3 years despite late recurrences, which were more pronounced in the radiation group.     

Abciximab administration and clinical outcomes after percutaneous intervention for in-stent restenosis.

Abciximab therapy improves clinical outcomes after percutaneous interventions for de novo coronary artery disease. We sought to determine whether clinical outcomes after percutaneous intervention for in-stent restenosis are affected by abciximab administration. Between January 1996 and July 1999, 322 consecutive patients underwent percutaneous intervention for in-stent restenosis; 157 patients received abciximab and 165 patients were treated without abciximab based on operator discretion. Baseline clinical and angiographic variables and type of percutaneous intervention were recorded. Follow-up information was obtained and clinical endpoints were recorded. A multivariate analysis was performed to determine the independent variables associated with adverse clinical outcomes. Baseline clinical and angiographic variables were similar in both groups. Patients who received abciximab were more likely to be treated with rotational atherectomy and less likely to have only balloon angioplasty or repeat stenting. Mean follow-up duration was 19 +/- 12 months. There were no significant differences in the incidence of angina/myocardial infarction (29% vs. 30%; P = 0.9), target vessel revascularization (18% vs. 21%; P = 0.5), death (8% vs. 7%; P = 0.4), or major adverse cardiovascular events (38% vs. 39%; P = 0.9) in both groups. Abciximab administration was not an independent variable associated with adverse outcomes. In this observational study, clinical outcomes after percutaneous intervention for in-stent restenosis did not seem to be affected by abciximab administration. Randomized trials are needed to identify the role of platelet glycoprotein IIb/IIIa inhibitors in the management of in-stent restenosis.