The platelet function dose-response to abciximab during percutaneous coronary revascularization is variable.

The platelet function dose-response to incremental abciximab (Reopro, Eli Lilly/Centocor, Indianapolis, IN) bolus dosing during percutaneous coronary intervention (PCI) was evaluated in 85 patients using a point-of-service platelet function assay. Patients received incremental bolus doses of abciximab at 10- to 20-min intervals; platelet function was measured at 10-min intervals during dosing. The percentage of patients achieving > or = 80% inhibition of platelet function after 50%, 75%, and 100% of a standard abciximab bolus was 40%, 87%, and 95%, respectively. There were no significant associations between the platelet function dose-response to abciximab and age, weight, platelet count, hematocrit, heparin dose, peak activated clotting time, thienopyridine use prior to PCI, gender, cigarette smoking, diabetes mellitus, or clinical syndrome. This study demonstrated significant interpatient variability in platelet function dose-response to abciximab with a substantial proportion (87%) of patients achieving high-level platelet function inhibition with less than the standard abciximab bolus dose.

A randomized, placebo-controlled trial of enoxaparin after high-risk coronary stenting: the ATLAST trial.

OBJECTIVES: We performed a multicenter, double-blind placebo-controlled trial to examine the efficacy and safety of enoxaparin in patients at high risk for stent thrombosis (ST). BACKGROUND: The optimal antithrombotic regimen for such patients is unknown. METHODS: We randomized 1,102 patients with clinical, angiographic or ultrasonographic features associated with an increased risk of ST to receive either twice-daily injections of weight-adjusted enoxaparin or placebo for 14 days after stenting. All patients received aspirin and ticlopidine. The primary end point was a 30-day composite end point of death, myocardial infarction (MI) or urgent revascularization. RESULTS: The target enrollment for the study was 2,000 patients. However, the trial was terminated prematurely at 1,102 patients after interim analysis revealed an unexpectedly low event rate. The primary outcome occurred in 1.8% enoxaparin-treated patients versus 2.7% treated with placebo (odds ratio [OR] 0.66; 95% confidence interval [CI] 0.29 to 1.5, p = 0.30); for death or MI the rates were 0.9% vs. 2.2%, respectively (OR 0.41, 95% CI 0.14 to 1.2, p =0.13); and for MI, 0.4% vs. 1.6%, respectively (OR 0.22, 95% CI 0.05 to 0.99, p = 0.04). The groups had comparable rates of major bleeding (3.3% for enoxaparin, 1.6% for placebo, p =0.08), but minor nuisance bleeding was increased with enoxaparin (25% vs. 5.1%, p < 0.001). CONCLUSIONS: The clinical outcomes of patients at increased risk of ST are more favorable than previously reported, rendering routine oral antiplatelet therapy adequate for most. However, given its relative safety and potential to reduce the risk of subsequent infarction, a 14-day course of enoxaparin may be considered for carefully selected patients.

Brachytherapy for in-stent restenosis through the internal mammary artery.

We report five cases treated with brachytherapy through the internal mammary artery (IMA) for in-stent restenosis at the distal anastomosis (n = 3) and in the left anterior descending coronary artery beyond the distal anastomosis (n = 2). After angioplasty, catheter-based gamma radiation was performed. There was no delivery failure of the radiation system. All cases had angiographic success and no procedural or in-hospital complications.

Radiation therapy to inhibit restenosis: early clinical results.

BACKGROUND: Although several early trials indicate that treatment of restenosis with radiation therapy is safe and effective, the long-term impact of this new technology has been questioned. The objective of this report is to document angiographic and clinical outcome 3 years after treatment of restenosis of stented coronary arteries with catheter-based iridium-192 (192Ir). METHODS: A double-blind, randomized trial compared 192Ir with placebo sources in patients with previous restenosis after coronary angioplasty. Over a 9-month period, 55 patients were enrolled; 26 were randomized to 192Ir and 29 to placebo. RESULTS: At 3-year follow-up, target-lesion revascularization was significantly lower in the 192Ir group (15.4% vs. 48.3%; p < 0.01). The dichotomous restenosis rate at 3-year follow-up was also significantly lower in 192Ir patients (33% vs. 64%; p < 0.05). In a subgroup of patients with 3-year angiographic follow-up not subjected to target-lesion revascularization by the 6-month angiogram, the mean minimal luminal diameter between 6 months and 3 years decreased from 2.49 +/- 0.81 mm to 2.12 +/- 0.73 mm in 192Ir patients, but was unchanged in placebo patients. CONCLUSIONS: The early clinical benefits observed after treatment of coronary restenosis with 192Ir appear durable at late follow-up. Angiographic restenosis continues to be significantly reduced in 192Ir-treated patients, but a small amount of late loss was observed between the 6-month and 3-year follow-up time points. No events occurred in the 192Ir group to suggest major untoward effects of vascular radiotherapy. At 3-year follow-up, vascular radiotherapy continues to be a promising new treatment for restenosis.

Point-of-care measured platelet inhibition correlates with a reduced risk of an adverse cardiac event after percutaneous coronary intervention: results of the GOLD (AU-Assessing Ultegra) multicenter study.

BACKGROUND: The optimal level of platelet inhibition with a glycoprotein (GP) IIb/IIIa antagonist necessary to minimize thrombotic complications in patients undergoing a percutaneous coronary intervention (PCI) is currently unknown. METHODS AND RESULTS: Five hundred patients undergoing a PCI with the planned use of a GP IIb/IIIa inhibitor had platelet inhibition measured at 10 minutes, 1 hour, 8 hours, and 24 hours after the initiation of therapy with the Ultegra Rapid Platelet Function Assay (Accumetrics). Major adverse cardiac events (MACES: composite of death, myocardial infarction, and urgent target vessel revascularization) were prospectively monitored, and the incidence correlated with the measured level of platelet function inhibition at all time points. One quarter of all patients did not achieve >/=95% inhibition 10 minutes after the bolus and experienced a significantly higher incidence of MACEs (14.4% versus 6.4%, P=0.006). Patients whose platelet function was <70% inhibited at 8 hours after the start of therapy had a MACE rate of 25% versus 8.1% for those >/=70% inhibited (P=0.009). By multivariate analysis, platelet function inhibition >/=95% at 10 minutes after the start of therapy was associated with a significant decrease in the incidence of a MACE (odds ratio 0.46, 95% CI 0.22 to 0.96, P=0.04). CONCLUSIONS: Substantial variability in the level of platelet function inhibition is achieved with GP IIb/IIIa antagonist therapy among patients undergoing PCI. The level of platelet function inhibition as measured by a point-of-care assay is an independent predictor for the risk of MACEs after PCI.

Long-term vessel response to a self-expanding coronary stent: a serial volumetric intravascular ultrasound analysis from the ASSURE Trial.A Stent vs. Stent Ultrasound Remodeling Evaluation.

OBJECTIVES: We sought to investigate the in vivo mechanical properties of a new self-expanding coronary stent (RADIUS) and, particularly, the subsequent vessel response over time. BACKGROUND: Preclinical studies have suggested that self-expanding stents may produce less vessel wall injury at initial deployment, leading to larger follow-up lumens than with balloon-expandable stents. However, the influence of the chronic stimulus from self-expanding stents on the vessel wall remains unknown. METHODS: Sixty-two patients were randomly assigned to either the RADIUS self-expanding stent group (n = 32) or the Palmaz-Schatz balloon-expandable stent group (n = 30). Intravascular ultrasound was performed after stent deployment and at six-month follow-up. RESULTS: At follow-up, the RADIUS stents had increased 23.6% in overall volume, while the Palmaz-Schatz stents had remained unchanged. Due to the greater mean neointimal area (3.0 +/- 1.7 mm2 vs. 1.9 +/- 1.2 mm2, p = 0.02) in the RADIUS group, no significant difference in net late lumen loss was observed between the two groups. On the other hand, analysis at the peristent margins demonstrated that mean late loss was significantly smaller in the RADIUS group than it was in the Palmaz-Schatz group (0.1 +/- 2.1 mm2 vs. 1.9 +/- 2.4 mm2, p = 0.02). CONCLUSIONS: Serial volumetric IVUS revealed that the RADIUS stents continued to enlarge during the follow-up period. In this stent implantation protocol, this expansion was accompanied by a greater amount of neointima than the Palmaz-Schatz stents, resulting in similar late lumen loss in both configurations. In the peristent margins, however, late lumen loss was minimized with the RADIUS stents.

Source displacement during the cardiac cycle in coronary endovascular brachytherapy.

PURPOSE: Preliminary clinical trials employing catheter-based endovascular brachytherapy show promising results in reducing restenosis after coronary intervention. Failure analysis of these studies showed a significant number of failures at the treatment margin. It is hypothesized that one of the possible causes for marginal failure is the longitudinal seed movement during the brachytherapy procedure. In this study a quantitative analysis was performed to determine the magnitude of the source displacement during the cardiac cycle. METHODS AND MATERIALS: Cine-angiograms of the Iridium-192 (Ir-192) active source seeds or dummy source seeds in place were reviewed frame by frame for 30 patients enrolled from various clinical trials using the Cordis catheter delivery system with a Ir-192 seed ribbon. The proximal and distal source points were measured in reference to branching vessels closest to the respective seed during the contrast phase of the cine-angiogram. The two frames showing the maximum source displacement were captured. After appropriate demagnification, longitudinal source displacement was measured. The data were tabulated for proximal vs. distal ends and for different coronary vessels. RESULTS: The longitudinal source displacement is significant with overall mean and standard deviation of 1.1 and 0.8 mm, respectively. The range is from 0.0 to 5.4 mm. CONCLUSION: The contribution of source movement should be included into the treatment length to avoid "geographic miss" and the subsequent marginal failure.

Localized intracoronary gamma-radiation therapy to inhibit the recurrence of restenosis after stenting.

BACKGROUND: Although the frequency of restenosis after coronary angioplasty is reduced by stenting, when restenosis develops within a stent, the risk of subsequent restenosis is greater than 50 percent. We report on a multicenter, double-blind, randomized trial of intracoronary radiation therapy for the treatment of in-stent restenosis. METHODS: Of 252 eligible patients in whom in-stent restenosis had developed, 131 were randomly assigned to receive an indwelling intracoronary ribbon containing a sealed source of iridium-192, and 121 were assigned to receive a similar-appearing nonradioactive ribbon (placebo). RESULTS: The primary end point, a composite of death, myocardial infarction, and the need for repeated revascularization of the target lesion during nine months of follow-up, occurred in 53 patients assigned to placebo (43.8 percent) and 37 patients assigned to iridium-192 (28.2 percent, P=0.02). However, the reduction in the incidence of major adverse cardiac events was determined solely by a diminished need for revascularization of the target lesion, not by reductions in the incidence of death or myocardial infarction. Late thrombosis occurred in 5.3 percent of the iridium-192 group, as compared with 0.8 percent of the placebo group (P=0.07), resulting in more late myocardial infarctions in the iridium-192 group (9.9 percent vs. 4.1 percent, P=0.09). Late thrombosis occurred in irradiated patients only after the discontinuation of oral antiplatelet therapy (with ticlopidine or clopidogrel) and only in patients who had received new stents at the time of radiation treatment. CONCLUSIONS: Intracoronary irradiation with iridium-192 resulted in lower rates of clinical and angiographic restenosis, although it was also associated with a higher rate of late thrombosis, resulting in an increased risk of myocardial infarction. If the problem of late thrombosis within the stent can be overcome, intracoronary irradiation with iridium-192 may become a useful approach to the treatment of in-stent restenosis.

Early lumen loss after repeat coronary intervention for in-stent restenosis.

The purpose of this study was to compare the effects of balloon angioplasty versus repeat stenting on the early angiographic outcome in patients with in-stent restenosis. The treatment of in-stent restenosis using balloon angioplasty alone often yields excellent early results, but is associated with a high rate of late recurrence. In the SCRIPPS trial, patients with restenosis were treated either with balloon angioplasty alone or placement of additional stents to optimize angiographic results before randomization and exposure of the restenotic segment to gamma radiation or placebo. In patients undergoing repeat catheter based intervention for the treatment of in-stent restenosis, quantitative coronary angiography was used to compare the results of balloon angioplasty alone versus repeat stenting on early lumen loss. After a mean delay time interval of 71 min, the early loss was 0.35 +/- 0.34 mm in the balloon angioplasty alone group compared to 0.01 +/- 0.34 mm in the repeat-stenting group (P = 0.004). The early loss index in the balloon angioplasty alone group (12.8 +/- 12.9%) was significantly greater than in the repeat stenting group (0.7 +/- 12.1%; P = 0.003). Although balloon angioplasty for in-stent restenosis often provides excellent immediate angiographic results, luminal diameters are significantly reduced in the early time period after balloon dilatation. Repeat stenting nearly abolishes this early luminal loss.

Rotational atherectomy or balloon angioplasty in the treatment of intra-stent restenosis: BARASTER multicenter registry.

The BARASTER registry was formed to evaluate the initial success and long-term results of rotational atherectomy in the management of in-stent restenosis. Rotational atherectomy was used in 197 cases of in-stent restenosis: 46 with stand-alone rotational atherectomy or at most 1 atmosphere of balloon inflation (Rota strategy), and 151 with rotational atherectomy and adjunctive balloon angioplasty <1 atmosphere (Combination strategy). These were compared with 107 episodes of in-stent restenosis treated with balloon angioplasty alone. In this observational study, the use of Combination therapy was associated with a slightly higher initial success rate (95% vs. 87% with the Rota strategy and 89% with Balloons, P = 0.08). There was a reduction in one year clinical outcomes (death, myocardial infarction or target lesion revascularization) in the combination group (38% vs. 60% with Rota and 52% with balloons, P = 0.02). These data support a benefit of the strategy of debulking with rotational atherectomy followed by adjunctive balloon angioplasty, in the management of in-stent restenosis.

Balloon occlusion and transluminal aspiration of saphenous vein grafts to prevent distal embolization.

Distal embolization is a common complication of percutaneous intervention in saphenous vein grafts. This may lead to the "no reflow" phenomenon and subsequent myocardial infarction. We describe a case in which we occluded the distal portion of a saphenous vein graft with a balloon to prevent distal embolization, performed percutaneous transluminal coronary angioplasty, and then successfully aspirated the particulate debris with a Dorros/Probing catheter.

Final results of the Can Routine Ultrasound Influence Stent Expansion (CRUISE) study.

BACKGROUND: Intravascular ultrasound (IVUS) can assess stent geometry more accurately than angiography. Several studies have demonstrated that the degree of stent expansion as measured by IVUS directly correlated to clinical outcome. However, it is unclear if routine ultrasound guidance of stent implantation improves clinical outcome as compared with angiographic guidance alone. METHODS AND RESULTS: The CRUISE (Can Routine Ultrasound Influence Stent Expansion) study, a multicenter study IVUS substudy of the Stent Anti-thrombotic Regimen Study, was designed to assess the impact of IVUS on stent deployment in the high-pressure era. Nine centers were prospectively assigned to stent deployment with the use of ultrasound guidance and 7 centers to angiographic guidance alone with documentary (blinded) IVUS at the conclusion of the procedure. A total of 525 patients were enrolled with completed quantitative coronary angiography, quantitative coronary ultrasound, and clinical events adjudicated at 9 months for 499 patients. The IVUS-guided group had a larger minimal lumen diameter (2.9+/-0.4 versus 2.7+/-0. 5 mm, P<0.001) by quantitative coronary angiography and a larger minimal stent area (7.78+/-1.72 versus 7.06+/-2.13 mm(2), P<0.001) by quantitative coronary ultrasound. Target vessel revascularization, defined as clinically driven repeat interventional or surgical therapy of the index vessel at 9 month-follow-up, occurred significantly less frequently in the IVUS-guided group (8.5% versus 15.3%, P<0.05; relative reduction of 44%). CONCLUSIONS: These data suggest that ultrasound guidance of stent implantation may result in more effective stent expansion compared with angiographic guidance alone.

Nonsurgical removal of angio-seal device after intra-arterial deposition of collagen plug.

Intra-arterial deposition of collagen may complicate deployment of the Angio-Seal arterial closure device. This problem has traditionally been treated surgically. We describe a case of nonsurgical Angio-Seal removal from the femoral artery and outline steps to prevent and manage intra-arterial collagen plug deposition.

The SCRIPPS trial--catheter-based radiotherapy to inhibit coronary restenosis.

The SCRIPPS trial is a randomized, double-blind, placebo-controlled trial evaluating the impact of gamma radiation to inhibit in-stent restenosis. Fifty-five patients were enrolled; twenty-six were assigned to receive catheter-based radiation with Ir-192 and 29 were treated with placebo. Angiographic restenosis in the Ir-192-treated patients was significantly reduced at six months (17% vs. 54%; p = 0.01), with the results sustained at 3-year follow-up (33.3% vs. 63. 6%; p<0.05). Likewise, the composite clinical endpoint of death, myocardial infarction or target lesion revascularization was also commensurately lower in the treated group as compared to the placebo group (23.1% vs. 55.2%; p = 0.01). Late angiography revealed no perforation, aneurysm or pseudoaneurysm or special safety issues unique to radiotherapy.

Three-year clinical and angiographic follow-up after intracoronary radiation : results of a randomized clinical trial.

BACKGROUND: Although several early trials indicate treatment of restenosis with radiation therapy is safe and effective, the long-term impact of this new technology has been questioned. The objective of this report is to document angiographic and clinical outcome 3 years after treatment of restenotic stented coronary arteries with catheter-based (192)Ir. METHODS AND RESULTS: A double-blind, randomized trial compared (192)Ir with placebo sources in patients with previous restenosis after coronary angioplasty. Over a 9-month period, 55 patients were enrolled; 26 were randomized to (192)Ir and 29 to placebo. At 3-year follow-up, target-lesion revascularization was significantly lower in the (192)Ir group (15. 4% versus 48.3%; P<0.01). The dichotomous restenosis rate at 3-year follow-up was also significantly lower in (192)Ir patients (33% versus 64%; P<0.05). In a subgroup of patients with 3-year angiographic follow-up not subjected to target-lesion revascularization by the 6-month angiogram, the mean minimal luminal diameter between 6 months and 3 years decreased from 2.49+/-0.81 to 2.12+/-0.73 mm in (192)Ir patients but was unchanged in placebo patients. CONCLUSIONS: The early clinical benefits observed after treatment of coronary restenosis with (192)Ir appear durable at late follow-up. Angiographic restenosis continues to be significantly reduced in (192)Ir-treated patients, but a small amount of late loss was observed between the 6-month and 3-year follow-up time points. No events occurred in the (192)Ir group to suggest major untoward effects of vascular radiotherapy. At 3-year follow-up, vascular radiotherapy continues to be a promising new treatment for restenosis.

Effect of intracoronary gamma-radiation therapy on in-stent restenosis: An intravascular ultrasound analysis from the gamma-1 study.

BACKGROUND: The aim of this study was to use serial volumetric intravascular ultrasound to evaluate the effect of gamma-radiation on recurrent in-stent restenosis. METHODS AND RESULTS: After successful reintervention, patients were randomized to receive either (192)Ir or placebo. Intravascular ultrasound studies with motorized pullback (0.5 mm/s) were performed immediately after irradiation and at 8-month follow-up in 70 patients. Paired volumetric analysis of the stented segment and of 5-mm proximal and distal reference segments was performed; this included measurements of the external elastic membrane, lumen, plaque and media (external elastic membrane minus lumen), stent, and intimal hyperplasia (stent minus lumen). Baseline proximal reference, stent, and distal reference measurements were similar in both groups. The changes in proximal and distal reference measurements of the external elastic membrane, plaque and media, and lumen areas were similar in both groups. However, the decrease in stented segment lumen volume was less in the (192)Ir patients than the placebo patients (-25+/-34 mm(3) versus -48+/-42 mm(3); P:=0.0225), and the increase in the volume of intimal hyperplasia in the stented segment was less in the (192)Ir patients than in the placebo patients (28+/-37 mm(3) versus 50+/-40 mm(3); P:=0.0352). When averaged over the length of the stented segment (32+/-13 mm versus 33+/-14 mm; P:=0.9), the increase in mean area of intimal hyperplasia was 0.8+/-1.0 mm(2) in the (192)Ir group and 1.6+/-1.2 mm(2) in the control group (P:=0.0065). Late stent-vessel wall malapposition was noted in one placebo patient and no (192)Ir patients. CONCLUSIONS: gamma-Radiation therapy can effectively prevent recurrent in-stent restenosis by inhibiting neointimal formation within the stent. At the stent edge, there were no significant differences between (192)Ir and placebo patients.

Quantitative angiographic analysis of stent restenosis in the Scripps Coronary Radiation to Inhibit Intimal Proliferation Post Stenting (SCRIPPS) Trial.

To identify luminal dimension changes occurring within the stent alone and within the stent + margin segment, we reviewed the quantitative angiographic results obtained from the Scripps Coronary Radiation to Inhibit Proliferation Post Stenting (SCRIPPS) trial, a prospective randomized trial assessing the effect of iridium-192 (Ir-192) on the prevention of stent restenosis. Fifty-five patients were randomly assigned to receive Ir-192 or placebo sources after successful intervention. Procedural and 6-month follow-up cineangiograms were quantitatively reviewed in 52 patients to identify changes within the stent and the stent + margin segment. The percent diameter stenosis was lower within the stent than within the stent + margin segment after the procedure (6 +/- 22% vs 21+/- 15%, p <0.0001) and at follow-up (28 +/- 29% vs 42 +/- 21%, p <0.0001). As a result, a lower restenosis rate was found within the stent than within the stent + margin (25% vs 37%, p <0.0001); isolated stent margin restenosis occurred in 11.5% of lesions. Treatment with Ir-192 reduced restenosis within the stent (8% vs 39%; p = 0.010) and within the stent + margin segment (17% vs 54%; p = 0.010); the reduction in restenosis at the margin only (8.3% vs 14.3%, p = 0.503) was not significant. The lowest relative risk for restenosis resulting from Ir-192 occurred within the stent (0.21; 95% confidence interval [CI] 0.05 to 0.86) compared with the stent + margin segment (0.31; 95% CI 0.12 to 0.81) or the stent margin (0.58; 95% CI 0.12 to 2.91). In the SCRIPPS trial, 32% of restenosis occurred at the stent margins. Treatment with Ir-192 reduced restenosis primarily within the stent rather than the margin. Whether extending the treatment length to fully include the stent margins will further reduce restenosis requires further study.