Effect of technique on outcomes following bioresorbable vascular scaffold implantation: analysis from the ABSORB trials

BACKGROUND: Procedural technique may affect clinical outcomes after bioresorbable vascular scaffold (BVS) implantation. Prior studies suggesting such a relationship have not adjusted for baseline patient and lesion characteristics that may have influenced operator choice of technique and outcomes. OBJECTIVES: This study sought to determine whether target lesion failure (TLF) (cardiac death, target-vessel myocardial infarction, or ischemia-driven target lesion revascularization) and scaffold thrombosis (ScT) rates within 3 years of BVS implantation are affected by operator technique (vessel size selection and pre- and post-dilation parameters). METHODS: TLF and ScT rates were determined in 2,973 patients with 3,149 BVS-treated coronary artery lesions from 5 prospective studies (ABSORB II, ABSORB China, ABSORB Japan, ABSORB III, and ABSORB Extend). Outcomes through 3 years (and between 0 to 1 and 1 to 3 years) were assessed according to pre-specified definitions of optimal technique (pre-dilation, vessel sizing, and post-dilation). Multivariable analysis was used to adjust for differences in up to 18 patient and lesion characteristics...

Relation between bioresorbable scaffold sizing using QCA-Dmax and clinical outcomes at 1 year in 1,232 patients from 3 study cohorts (ABSORB Cohort B, ABSORB EXTEND, and ABSORB II)

BACKGROUND:Assessment of pre-procedural Dmax of proximal and distal sites has been used for Absorb scaffold size selection in the ABSORB studies.METHODS:A total of 1,248 patients received Absorb scaffolds in the ABSORB Cohort B (ABSORB Clinical Investigation, Cohort B) study (N = 101), ABSORB EXTEND (ABSORB EXTEND Clinical Investigation) study (N = 812), and ABSORB II (ABSORB II Randomized Controlled Trial) trial (N = 335). The incidence of major adverse cardiac events (MACE) (a composite of cardiac death, any myocardial infarction [MI], and ischemia-driven target lesion revascularization) was analyzed according to the Dmax subclassification of scaffold oversize group versus scaffold nonoversize group...

Endovascular brachytherapy in coronary arteries: the Rotterdam experience.

Purpose: The use of endovascular coronary brachytherapy to prevent restenosis following percutaneous transluminal coronary angioplasty (PTCA) began in April 1997 at the Department of Interventional Cardiology of the Thoraxcenter at the University Hospital of Rotterdam. This article reviews the more than 250 patients that have been treated so far.Methods and Materials: The Beta-Cath System (Novoste), a manual, hydraulic afterloader with 12 90Sr seeds, was used in the Beta Energy Restenosis Trial (BERT-1.5, n=31), for compassionate use (n=25), in the Beta-Cath System trial (n=27) and in the Beta Radiation in Europe (BRIE, n=14). Since the Beta-Cath System has been commercialized in Europe, 57 patients have been treated and registered in RENO (Registry Novoste). In the Proliferation Reduction with Vascular Energy Trial (PREVENT), 37 patients were randomized using the Guidant-Nucletron remote control afterloader with a 32P source wire and a centering catheter. Radioactive 32P coated stents have been implanted in 102 patients. In the Isostent Restenosis Intervention Study 1 (IRIS 1), 26 patients received a stent with an activity of 0.75-1.5 µCi, and in the IRIS 2 (European 32P dose response trial), 40 patients were treated with an activity of 6-12 µCi. In two consecutive pilot trials, radioactive stents with non-radioactive ends (cold-end stents) and with ends containing higher levels of activity (hot-end stents) were implanted in 21 and 17 patients, respectively.Results: In the BERT-1.5 trial, the radiation dose, prescribed at 2 mm from the source train (non-centered), was 12 Gy (10 patients), 14 Gy (10 patients) and 16 Gy (11 patients). At 6-month follow-up, 8 out of 28 (29%) patients developed restenosis. The target lesion revascularization rate (TLR) was 7 out of 30 (23%) at 6 months and 8 out of 30 (27%) at 1 year. Two patients presented with late thrombosis in the first year. For compassionate use patients, a restenosis rate (RR) of 53% was observed. In the PREVENT trial, 34 of 37 patients underwent an angiographic 6-month follow-up. The doses prescribed at 0.5 mm depth into the vessel wall were 0 Gy (8), 28 Gy (9), 35 Gy (11) and 42 Gy (8). TLR was 14% in the irradiated patients and 25% in the placebo group. One patient developed late thrombosis. In the IRIS 1 trial, 23 patients showed an RR of 17% (in-stent). In the IRIS 2 trial, in-stent restenosis was not seen in 36 patients at 6-month follow-up. However, a high RR (44%) was observed at the stent edges.Conclusions: The integration of vascular brachytherapy in the catheterization laboratory is feasible and the different treatment techniques that are used are safe. Problems, such as edge restenosis and late thrombotic occlusion, have been identified as limiting factors of this technique. Solutions have been suggested and will be tested in future trials.

Late thrombotic occlusion of a malapposed stent 10 months after intracoronary brachytherapy.

We report a patient who received a stent following intracoronary 3-irradiation. Despite a good initial angiographic result, the stent appeared to be not fully expanded on intravascular ultrasound imaging at 6-month follow-up. Four months later, sudden thrombotic occlusion occurred shortly after aspirin cessation.

Ultrasound Appearances of Coronary Stents as Obtained by Three-Dimensional Intracoronary Ultrasound Imaging In Vitro.

Intracoronary ultrasound (ICUS) is an imaging technique which can provide a cross-sectional image of coronary arteries and implanted stents. Different stents may have individual ICUS imaging characteristics. To investigate the imaging characteristics and three-dimensional (3-D) reconstruction of different coronary stent designs, we examined 26 different stents using ICUS in vitro. All stents could be well visualized with planar ICUS. In 18 stents, 3-D imaging succeeded in reconstructing the spatial stent architecture. This was not possible in the other 8 stents, most probably because of predominantly transversally-orientated strut architecture, the small size of the strut wire width, the limited ICUS lateral catheter resolution, and the smoothing and interpolation algorithms applied for 3-D reconstruction. ICUS in vitro provides a means of identifying coronary stent structures which may be applicable in vivo. Three-D reconstruction of the entire stent architecture in vitro can be achieved in stents with mesh or slotted tube design, while stents with coil design and thin strut wires can only be partially reconstructed.

Clinical and Angiographic Results with the Multi-Linkª Coronary Stent System Ñ The West European Stent Trial (WEST).

BACKGROUND: The objectives for the West European Stent Trial (WEST) were to assess the safety and efficacy of the new ACS Multi-Linkª coronary stent system with regards to bleedings and vascular complications and incidence of major adverse cardiac events during 12 months follow-up. METHODS AND RESULTS: The balloon-expandable Multi-Link stent is made from a single hypotube and is composed of 316 L stainless steel. In an open, non-randomized, multicenter registry, 102 patients with angina pectoris to be treated with this stent were recruited from 7 European centers. Following stent implantation, patients were given heparin infusion and oral coumadin treatment was maintained for 3 months. Procedural success was achieved in 100 of the 102 patients (98%). One patient had subacute stent thrombosis and 6 patients had major bleeds during the hospital stay. All patients were alive at 12 months and 85% were free of angina pectoris. Nineteen patients (19%) reached a primary clinical endpoint; four patients underwent bypass surgery (two in connection with the stent procedure), four patients suffered an acute myocardial infarction and 11 had a repeat angioplasty of the target vessel. Quantitative angiography showed that the minimum lumen diameter had decreased from 2.66 +/- 0.34 mm after stent deployment to 2.02 +/- 0.58 mm at 6 months and the percent diameter stenosis had increased from 18 +/- 7% to 33 +/- 16%. The in-stent restenosis rate was 12% and appearance of a stenosis in the target vessel outside the stent occurred in an additional 5%. CONCLUSION: The WEST study has demonstrated a high degree of safety and efficacy of the Multi-Link stent with a low incidence of complications and clinical events during follow-up. The results compare favorably with data from other stents.

Clinical and Angiographic Results with the Multi-Link Stent Implanted under Intravascular Ultrasound Guidance (West-2 Study).

In view of the side effects of ticlopidine, stenting with the sole use of aspirin as post-stent treatment, has been attempted under the guidance of intravascular imaging to guarantee the optimization of the deployment. It was also hypothesized that optimal stenting under IVUS guidance would subsequently reduce the restenosis rate. With these aims the WEST-2 trial using the ACS MULTI-LINK stent was designed. This stent is composed of multiple corrugated rings connected to multiple links Ñ a design that combines radial strength, flexibility and conformability. In WEST-2, between February 1996 and August 1996, 18 centers enrolled 165 patients with stable or stabilized unstable angina and a single de novo lesion in vessel sizes ³ 2.75 mm. Optimal stenting was assessed using predefined QCA (DS% post-stent ³ 15% and stent/artery ratio ³ 1) and IVUS criteria. Patients fulfilling all criteria were treated with aspirin alone. MACE (death, MI, target lesion revascularization) as well as the restenosis rate were assessed at 6 months. In view of the results it may be concluded that the use of aspirin alone as post-stent treatment is safe when preset IVUS criteria are achieved. The target lesion revascularization rate, the restenosis percentage and the incidence of MACE encountered in this registry are among the lowest observed so far.

Three-Dimensional Intravascular Ultrasound Analysis of Coronary Stent Deployment and In-Stent Neointimal Volume: Current Clinical Practice and the Concepts of TRAPIST, ERASER, and ITALICS.

Intravascular ultrasound (IVUS) permits the detailed examination of coronary stent apposition and expansion in vivo. IVUS assessment of the extent and distribution of in-stent neointima at follow-up is an ideal model for the evaluation of new antiproliferative drugs that aim at a reduced in-stent neointimal hyperplasia. Recently, automated systems for three-dimensional reconstruction and analysis of IVUS images have been developed. This manuscript illustrates the methodology and clinical use of automated three-dimensional IVUS analysis systems during coronary stenting, and highlights the first randomized trials to apply such a technique for the assessment of in-stent neointima.

'Navius' kissing stents for coronary bifurcation stenosis, recreating a new metallic carina: an IVUS-assessed case report.

We report a case of implantation of a new design of stent which allows creation of a double-hemispheric lumen for the treatment of a bifurcational stenosis. The unfavourable outcome following the implantation of this stent is described.

Stent implantation in acute myocardial infarction using a heparin-coated stent: a pilot study as a preamble to a randomized trial comparing balloon angioplasty and stenting.

Preliminary experience with primary stenting in myocardial infarction has suggested a greater benefit in clinical outcome than has been obtained with direct balloon angioplasty. However, subacute thrombosis (SAT) remains a limitation for this new mode of therapy. In the BENESTENT II Pilot and main trials, the incidence of SAT with the heparin-coated Palmaz-Schatz stent was only 0.15%. Therefore, as a preamble to a large randomized trial, the feasibility and safety of the use of the Heparin-Coated Palmaz-Schatz trade mark Stent in Acute Myocardial Infarction (AMI) was tested in 101 patients enrolled between April and September 1996 in 18 clinical centres. In 101 stent-eligible AMI patients, as dictated by protocol, a heparin-coated stent was implanted. The primary objectives were to determine the in-hospital incidence of major adverse cardiac events (MACE: death, MI, target lesion revascularization) and bleeding complications, while the secondary objectives were the procedural success rate and the MACE, the restenosis and reocclusion rates at 6.5 months. Stent implantation (n 3 129 stents) was successful in 97 patients of the 101 who were included in this trial. During their hospital stay, two patients died and no patient experienced re-infarction, ischaemia prompting re-PTCA or CABG. Four patients suffered a bleeding complication, three major and one minor, of whom three required surgical repair. At 210 days follow-up, 81% of the patients were event free. At 6.5 months restenosis was documented in 18% of the 88 patients who underwent follow-up angiography, including three total occlusions. The results, both with respect to QCA and the occurrence of MACE, compare favourably with studies using elective stenting in both stable and unstable angina patients. As a result of this pilot study, a large randomized trial comparing direct balloon angioplasty with direct stenting in 900 patients with AMI was initiated in December 1996.

Results of a Meta-Analysis of Trapidil, a PDGF Inhibitor Ñ A Sufficient Reason for a Second Look to the Pharmacological Approach to Restenosis.

Restenosis in 30%Ð40% of patients remains the major limitation to the long-term success of balloon angioplasty (PTCA) in patients with coronary artery disease. So far, only coronary stent implantation has established its role as an effective strategy to prevent restenosis after PTCA. In contrast to numerous pharmacological strategies that all have failed to demonstrate a convincing reduction in the rate of restenosis, trapidil, a PDGF inhibitor, has shown promising and conclusive results in animal models as well as in three human trials published between 1992 and 1994. Although the results of the human trials showed trapidil to be capable of reducing restenosis after PTCA by 40%Ð53% compared to control patients, the compound is not well known and little used in interventional cardiology. Possible explanations for this situation may include trapidilÕs non-availability in the United States and most European countries, the small number of trapidil trials and treated patients, as well as a probable perception of the medical community that a pharmacological approach to restenosis prevention is unlikely to work. Additionally, clinical expert behavior has often shown not to be synchronized with accumulating evidence of efficacy. The results of this meta-analysis, however, demonstrate trapidilÕs efficacy. The rate of per-patient restenosis in the trapidil group was more than halved as compared to controls (odds ratio 0.44, 95% confidence interval 0.29Ð0.66). Tolerability with trapidil was good, and the rare adverse events observed included gastric intolerance, thrombocytopenia, headache, and increased serum AST and ALT levels which were transient or subsided with cessation of treatment.

Clinical and Angiographic Results with the Multi-Linkª Coronary Stent System Ñ The West European Stent Trial (WEST).

BACKGROUND: The objectives for the West European Stent Trial (WEST) were to assess the safety and efficacy of the new ACS Multi-Linkª coronary stent system with regards to bleedings and vascular complications and incidence of major adverse cardiac events during 12 months follow-up. METHODS AND RESULTS: The balloon-expandable Multi-Link stent is made from a single hypotube and is composed of 316 L stainless steel. In an open, non-randomized, multicenter registry, 102 patients with angina pectoris to be treated with this stent were recruited from 7 European centers. Following stent implantation, patients were given heparin infusion and oral coumadin treatment was maintained for 3 months. Procedural success was achieved in 100 of the 102 patients (98%). One patient had subacute stent thrombosis and 6 patients had major bleeds during the hospital stay. All patients were alive at 12 months and 85% were free of angina pectoris. Nineteen patients (19%) reached a primary clinical endpoint; four patients underwent bypass surgery (two in connection with the stent procedure), four patients suffered an acute myocardial infarction and 11 had a repeat angioplasty of the target vessel. Quantitative angiography showed that the minimum lumen diameter had decreased from 2.66 +/- 0.34 mm after stent deployment to 2.02 +/- 0.58 mm at 6 months and the percent diameter stenosis had increased from 18 +/- 7% to 33 +/- 16%. The in-stent restenosis rate was 12% and appearance of a stenosis in the target vessel outside the stent occurred in an additional 5%. CONCLUSION: The WEST study has demonstrated a high degree of safety and efficacy of the Multi-Link stent with a low incidence of complications and clinical events during follow-up. The results compare favorably with data from other stents.

Argatroban During Percutaneous Transluminal Coronary Angioplasty: Results of a Dose-Verification Study.

Background. Thrombin is a key enzyme in thrombogenesis. In animals, specific antithrombotic therapy at the time of coronary angioplasty reduced the incidence of subacute occlusion and inhibited the restenosis response. Argatroban is a highly selective synthetic thrombin antagonist that binds in a competitive manner. This is a report of a dose-verification study, assessing the safety and feasibility of intravenous Argatroban administration in patients undergoing percutaneous transluminal coronary angioplasty. Methods. Before angioplasty an intravenous bolus of 30 µg/kg argatroban was administered, followed by a continuous infusion of 3.5 µg/kg/min for 72 hours. Bolus injection was repeated, and the infusion rate was increased in order to achieve an activated coagulation time (ACT) of over 300 seconds. Following interim analysis, the bolus and initial infusion rate for the subsequent treatment groups was determined. Study endpoints were the occurrence of adverse events, coagulation tests, and qualitative angiogram reading. Patients were monitored by continuous 12-lead electrocardiographic recording over 24 hours, and underwent control angiography 18-24 hours following angioplasty. Results. Four treatment groups, comprised of 2, 8, 9, and 11 patients, respectively, were studied. The first two patients were excluded from analysis, since the initial dose was ineffective to attain an ACT-authorizing coronary angioplasty. The group with the highest dosage received a 250 µg/kg intravenous bolus of argatroban, followed by a 4 hour infusion of 15 µg/kg/min. At 4 hours the infusion rate was lowered to 3.8 µg/kg/min and was continued for 68 hours without adjustment for catheter removal. The adverse event profile included myocardial infarction, aortocoronary bypass graft, bailout procedures, and repeat coronary angioplasty. Thrombin-time (TT), activated partial thromboplastin time (APTT), and prothrombin time (PT) were significantly related to argatroban plasma concentration, as demonstrated by regression analyses (R-square 0.64, 0.71, and 0.84, respectively). Prothrombin fragments 1 and 2 and thrombin-antithrombin III complex did not fit into a mathematical model, but showed slightly increased levels after reduction or cessation of the infusion rate. Conclusions. This dose-verification study, including 30 patients at four dose levels, indicated that argatroban infusion in coronary angioplasty patients can be administered safely, and results in an adequate and predictable level of anticoagulation.