Effects of locally administered argatroban on restenosis after balloon angioplasty: experimental and clinical study

1. This study was undertaken to evaluate the preventive effects of locally administered argatroban, a competitive inhibitor of thrombin-induced platelet activation, on restenosis after balloon angioplasty. 2. A hydrogel-coated balloon catheter was immersed three times in argatroban/saline solution (1 mg/mL) for 60 s, inflated to a pressure of 606 kPa and left in the rabbit common carotid artery for 1 min. The same procedure was performed, without drug, as a control. The pharmacokinetics of delivered argatroban in the arterial wall were assessed using [14C]-argatroban. Platelet deposition 2 h after balloon injury was quantified by fluorescence studies using antiplatelet antibody. Vascular smooth muscle cell (VSMC) proliferation 3 days after balloon injury was assessed by immunohistochemical staining for proliferative cell nuclear antigen (PCNA). In a clinical study, we divided 50 elective patients into two groups: argatroban and control. 3. In the experimental study, the mean quantities of argatroban at 0, 2 and 6 h after deflation were 24.63, 0.49 and 0.11 nmol/g wet weight of artery, respectively. Argatroban was undetected 24 h after deflation. Two hours after deflation, argatroban-treated arteries showed less platelet adhesion than saline-treated controls. The mean number of PCNA-positive cells was 16.9 and 43.8% in the argatroban and control groups, respectively (P < 0.01). In the clinical study, the mean late gain loss was 8.2 and 27.3% in the argatroban and control groups, respectively (P < 0.05). The mean late restenosis rate was 11.1 and 41.4% in the argatroban and control groups, respectively (P < 0.05). 4. These data suggest that blood coagulation plays a significant role in VSMC proliferation after balloon injury and that locally administered argatroban using hydrogel-coated balloon catheter may prevent post-percutaneous transluminal coronary angioplasty restenosis.     

Effects of octreotide treatment on restenosis after coronary angioplasty: results of the VERAS study. VErringerung der Restenoserate nach Angioplastie durch ein Somatostatin-analogon

BACKGROUND: The VERAS study (VErringerung der Restenoserate nach Angioplastie durch ein Somatostatin-analogon [Prevention of Restenosis Following Angioplasty With a Somatostatin Analogue]) was a placebo-controlled trial to evaluate the effects of octreotide for the prevention of restenosis after coronary angioplasty. Octreotide is a somatostatin analogue with antiproliferative properties on smooth muscle cell growth in vitro that limits myointimal thickening of arteries in balloon injury models. METHODS AND RESULTS: Patients received either octreotide or placebo, starting 1 hour before angioplasty and continued for 3 weeks. The minimal luminal diameters before and after angioplasty and at 6-month follow-up were analyzed with a digital quantitative algorithm. Of the initial 274 patients recruited, 217 (108 in the octreotide group and 109 in the placebo group) could be analyzed after a complete 6-month evaluation: the minimal luminal diameters were 1.67+/-0.57 mm in the octreotide-treated group and 1.66+/-0.64 mm in the placebo group (two-paired P=.70), and the relative losses were 0.16+/-0.22 and 0.13+/-0.21 (two-paired P=.27). The restenosis rates were also identical in both treatment groups: final diameter stenosis > or =50% (34.3% versus 33.9%, two-paired P=1.0), loss of > or =50% of the initial gain (34.3% versus 33.9%, two-paired P=1.0), and absolute reduction of minimal luminal diameter >0.72 mm (29.6% versus 24.8%, two-paired P=.45). Likewise, there was no difference with regard to the incidence of clinical events (death, myocardial infarction, bypass operations, reintervention). Octreotide was well tolerated, with the exception of gastrointestinal side effects, which were three times more common than in the placebo group. CONCLUSIONS: Octreotide did not reduce the angiographically determined restenosis rate or the incidence of major clinical events after coronary angioplasty.     

Endovascular beta-radiation to reduce restenosis after coronary balloon angioplasty: results of the beta energy restenosis trial (BERT)

BACKGROUND: In the porcine overstretch injury model of restenosis, endovascular beta-radiation reduces neointima formation. To determine whether this therapy could be applied to patients with coronary artery disease, a special device was developed to allow delivery of 12 encapsulated 90Sr/Y sources, measuring a total of 30 mm, to various sites within the coronary arterial tree. This study was designed to evaluate the feasibility of the delivery of 12, 14, or 16 Gy at 2 mm after balloon angioplasty of stenoses of native coronary vessels. METHODS AND RESULTS: Delivery of beta-radiation was attempted in 23 patients after successful balloon angioplasty. Source delivery was successful in 21 of the 23 patients (91%). There was no in-hospital or 30-day morbidity or mortality. Follow-up quantitative coronary arteriography in 20 patients demonstrated a late loss of 0.05 mm, a late loss index of 4%, and a restenosis rate of 15%. The use of the beta-emitter 90Sr/Y significantly reduced treatment time and operator exposure compared with previous trials with the gamma-emitter 192Ir. CONCLUSIONS: In this study, the administration of endovascular beta-radiation after angioplasty was safe and feasible and substantially altered the postangioplasty late lumen loss, resulting in a lower-than-expected rate of restenosis. On the basis of these encouraging results, a multicenter, randomized trial with operators and patients blinded to treatment assignment is planned.     

The impact of balloon material and lesion characteristics on the incidence of angiographic and clinical complications of coronary angioplasty

To assess the importance of balloon material used for percutaneous transluminal coronary angioplasty (PTCA), we compared the complication rates observed with low complaint plastomer (PM 300), intermediately compliant polyethylene (PE 600), and highly compliant polyolefin copolymer (POC) balloons. In a total of 1,650 procedures, one of these balloon materials was used to dilate 2,040 lesions. The dissection rate tended to be slightly lower with the use of more compliant balloon material. The total clinical complication rate (death, emergency coronary surgery, myocardial infarction, need for bail-out stenting or for prolonged heparin treatment, abrupt out-of-laboratory vessel closure) was 8.1%, 7.4%, and 4.2% in the procedures exclusively performed with PM 300 (N = 653), PE 600 (N = 543) and POC (N = 454) balloons, respectively (P = 0.03). In multivariate analysis, the use of less compliant balloon material emerged as an independent correlate of clinical complications (P = 0.007). However, the predictive power of the lesion complexity (B2, C versus A, B1) was four times stronger. In contrast to current concerns, the use of compliant balloon material seems at least as safe as the use of less compliant material.     

Clinical, experimental and physiopathological aspects of restenosis after coronary angioplasty

Restenosis is still the main limitation of coronary angioplasty. A comparison of clinical data and experimental observations from animal models showed the early, local and transient features of this phenomenon. Several hypotheses have been advanced to explain the mechanism. Intimal hyperplasia remains an important feature of restenosis in the human but probably does not play the exclusive role as used to be believed. Vascular remodelling which has several mechanisms seems to be a major contribution to reduction of the vessel lumen. The role of thrombosis remains controversial in the clinical setting but is an essential factor in the pig which is a very similar model to the human. Each of these different mechanisms participates in the development of restenosis but in proportion which remain to be defined.     

Acute angiographic and clinical results of long balloon percutaneous transluminal coronary angioplasty and adjuvant stenting for long narrowings

Historically, long coronary artery stenoses undergoing percutaneous transluminal coronary angioplasty (PTCA) are reported to have reduced procedural and clinical success in comparison with shorter lesions. The efficacy of long balloons (30 or 40 mm) in long lesions was evaluated. Eighty-two patients had 84 PTCA procedures with a primary long balloon. In all, 86 lesions were available for analysis. Data were collected prospectively on standard PTCA procedure forms. Coronary angiograms were reviewed and measured with digital calipers. Hospital charts were examined for complications. PTCA was performed in the left anterior descending artery in 44 cases (51%), the right coronary artery in 29 (34%) and the circumflex artery in 13 (15%). With the use of a modified classification system, 47 lesions (55%) were class C, 24 (28%) were class B2 and 15 (17%) were class B1. Mean lesion length was 22 +/- 11 mm (range 10 to 72), and 38 lesions (44%) were > or = 20 mm. Twelve patients received an intracoronary stent. The long balloon alone produced angiographic success (< 50% residual stenosis) in 77 lesions (90%). Angiographic success was achieved ultimately in all stenoses, using a stent in 7 patients and a short balloon in 2. There were 2 deaths (2%) and 1 Q-wave myocardial infarction (1%). One patient needed coronary artery bypass surgery. Clinical success without death, Q-wave infarction or bypass surgery was achieved in 83 of 86 procedures (97%). In conclusion, the use of long PTCA balloons with adjuvant stenting produced excellent results in these long stenoses. Lesion length was not a precursor of poor angiographic or clinical outcome.     

Pharmacological approaches to the prevention of restenosis after coronary angioplasty

In the absence of distant disease, therapeutic node dissections in malignant melanoma, i.e., dissections of regional nodal basins for palpable suspicious or biopsy-proven positive nodes, offer the chance of cure. The 5-year survival rates after therapeutic lymphadenectomy closely correlate with expected cure rates. Although they varied greatly in the literature, from 19% to 38%, the currently obtainable survival rates are in the upper ranges of this spectrum because patients now are closely followed-up and operated for early palpable nodal disease. Properly done, these procedures carry a low morbidity, but they should be done thoroughly to completely eradicate regional disease and avoid recurrences in the same nodal basin to achieve the maximum survival that is surgically attainable.     

Prevention and treatment of restenosis after percutaneous transluminal coronary angioplasty

Restenosis is a clinical problem after coronary angioplasty associated with major ischemic events or repeat interventions in 20-50% of the patients undergoing this procedure. Major efforts have been undertaken in the past decade to successfully prevent or treat restenosis but no pharmacologic approach to the problem has as yet been identified to be effective enough in clinical conditions. New strategies to cope with restenosis are targeted by local application of ionizing radiation which markedly reduces cell proliferation after angioplasty in animal experiments. Preliminary clinical trials indicate that endovascular radiation therapy is a safe and effective means to treat restenosis. Randomized, multicenter studies with long follow-up periods are needed to support these early results.     

Differences in restenosis propensity of devices for transluminal coronary intervention. A quantitative angiographic comparison of balloon angioplasty, directional atherectomy, stent implantation and excimer laser angioplasty. CARPORT, MERCATOR, MARCATOR, PARK, and BENESTENT Trial Groups

With the increasing clinical application of new devices for percutaneous coronary revascularization, maximization of the acute angiographic result has become widely recognized as a key factor in maintained clinical and angiographic success. What is unclear, however, is whether the specific mode of action of different devices might exert an additional independent effect on late luminal renarrowing. The purpose of this study was to investigate such a difference in the degree of provocation of luminal renarrowing (or 'restenosis propensity') by different devices, among 3660 patients, who had 4342 lesions successfully treated by balloon angioplasty (n = 3797), directional coronary atherectomy (n = 200), Palmaz-Schatz stent implantation (n = 229) or excimer laser coronary angioplasty (n = 116) and who also underwent quantitative angiographic analysis pre- and post-intervention and at 6-month follow-up. To allow valid comparisons between the groups, because of significant differences in coronary vessel size (balloon angioplasty = 2.62 +/- 0.55 mm, directional coronary atherectomy = 3.28 +/- 0.62 mm, excimer laser coronary angioplasty = 2.51 +/- 0.47 mm, Palmaz-Schatz = 3.01 +/- 0.44 mm; P < 0.0001), the comparative measurements of interest selected were the 'relative loss' in luminal diameter (RLoss = loss/vessel size) to denote the restenosis process, and the 'relative lumen at follow-up' (RLfup = minimal luminal diameter at follow up/vessel size) to represent the angiographic outcome. For consistency, lesion severity pre-intervention was represented by the 'relative lumen pre' (RLpre = minimal luminal diameter pre/vessel size) and the luminal increase at intervention was measured as 'relative gain' (relative gain = gain/ vessel size). Differences in restenosis propensity between devices was evaluated by univariate and multivariate analysis. Multivariate models were constructed to determine relative loss and relative lumen at follow-up, taking account of relative lumen pre-intervention, lesion location, relative gain, vessel size and the device used. In addition, model-estimated relative loss and relative lumen at follow-up at given relative lumen pre-intervention relative gain and vessel size, were compared among the four groups. Significant differences were detected among the groups both with respect to these estimates, as well as in the degree of influence of progressively increasing relative gain, on the extent of renarrowing (relative loss) and angiographic outcome (relative lumen at follow-up), particularly at higher levels of luminal increase (relative gain). Specifically, lesions treated by balloon angioplasty or Palmaz-Schatz stent implantation (the predominantly 'dilating' interventions) were associated with more favourable angiographic profiles than directional atherectomy or excimer laser (the mainly 'debulking' interventions). Significant effects of lesion severity and location, as well as the well known influence of luminal increase on both luminal renarrowing and late angiographic outcome were also noted. These findings indicate that propensity to restenosis after apparently successful intervention is influenced not only by the degree of luminal enlargement achieved at intervention, but by the device used to achieve it. In view of the clinical implications of such findings, further evaluation in larger randomized patient populations is warranted.     

The role of low-molecular-weight heparin in unstable angina, acute myocardial infarction and post-elective percutaneous transluminal coronary angioplasty

A young woman with a large astigmatic refractive error obtained no visual improvement with glasses. Repeated manifest refractions revealed persistent variations in the apparent cylinder axis. A suitable choice of spectacle frames facilitated a satisfactory outcome. The pitfalls inherent in the clinical specification of cylinder axis, and the potential visual consequences, are discussed.     

Multicenter investigation of coronary stenting to treat acute or threatened closure after percutaneous transluminal coronary angioplasty: clinical and angiographic outcomes

OBJECTIVES: This study reports on the initial experience with the Gianturco-Roubin flexible coronary stent. The immediate and 6-month efficacy of the device and the incidence of the complications of death, myocardial infarction, emergency coronary artery bypass surgery and recurrent ischemic events are presented. BACKGROUND: Abrupt or threatened vessel closure after coronary angioplasty is associated with increased risk of myocardial infarction, emergency coronary artery bypass graft surgery and in-hospital death. When dissection or prolapse of dilated plaque into the lumen is unresponsive to additional or prolonged balloon catheter inflation, coronary stenting offers a nonsurgical mechanical means to rapidly restore stable vessel geometry and adequate coronary blood flow. METHODS: From September 1988 through June 1991, 518 patients underwent attempted coronary stenting with the 20-mm long Gianturco-Roubin coronary stent for acute or threatened vessel closure after angioplasty. In 494 patients, one or more stents were deployed. Thirty-two percent of patients received stents for acute closure and 69% for threatened closure. RESULTS: Successful deployment was achieved in 95.4% of patients. Overall, stenting resulted in an immediate angiographic improvement in the diameter stenosis from 63 +/- 25% before stenting to 15 +/- 14% after stenting. Emergency coronary artery bypass graft surgery was required in 4.3% (21 of 493 patients). The incidence of in-hospital myocardial infarction (Q wave and non-Q wave) was 5.5% (27 of 493 patients). At 6 months, myocardial infarction was infrequent, occurring in 1.6% (8 of 493 patients). The incidence of in-hospital death was 2.2% (11 of 493 patients). Late death occurred in 7 patients (1.4%) and 34 patients (6.9%) required later bypass graft surgery. Complications included blood loss, primarily from the arterial access site, and subacute thrombosis of the stented vessel in 43 patients (8.7%). CONCLUSIONS: The early multicenter experience suggests that this stent is a useful adjunct to coronary angioplasty to prevent or minimize complications associated with flow-limiting coronary artery dissections previously correctable only by surgery. Although this study was not randomized, it demonstrated a high technical success rate and encouraging results with respect to the low incidence of emergency coronary artery bypass graft surgery and myocardial infarction.     

Early and late assessment of the Micro Stent PL coronary stent for restenosis and suboptimal balloon angioplasty

Dematiaceous fungi are being increasingly recognized as pathogens in organ transplant recipients. We describe a case of invasive esophagitis due to Cladophialophora bantiana in a small bowel transplant recipient and review a total of 34 cases of infections due to dematiaceous fungi in organ transplant recipients. The median time to the onset of fungal infection after transplantation was 22 months. Clinically, two distinct patterns of infections were observed: 79% of the patients had skin and/or soft-tissue infections or joint infections (predominantly due to Exophiala species), and 21% had systemic invasive infections (predominantly brain abscesses due to Ochroconis gallopavum [Dactylaria gallopava, Dactylaria constricta var. gallopava]). The overall mortality rate among the patients with skin and/or soft-tissue infections or joint infections and the patients with systemic invasive disease was 7% and 57%, respectively; two of five patients with brain abscesses were cured with antifungal therapy. Recognition of infections due to dematiaceous fungi is important since these infections, unlike invasive aspergillosis, may be more amenable to therapy.     

Role of angiographically identifiable thrombus on long-term luminal renarrowing after coronary angioplasty: a quantitative angiographic analysis

BACKGROUND: Experimental studies suggest that mural thrombus may be involved in postangioplasty restenosis. The aim of our study was to examine the role of angiographically identifiable thrombus in the clinical situation. METHODS AND RESULTS: The study population comprised 2950 patients (3583 lesions). The presence of angiographically identifiable thrombus either before or after the procedure was defined as the presence of a generalized haziness or filling defect within the arterial lumen. Restenosis was assessed by both a categorical (> 50% diameter stenosis at follow-up) and a continuous approach (absolute and relative losses). The study population included 160 lesions with and 3423 lesions without angiographically identifiable thrombus. The categorical restenosis rate was significantly higher in lesions containing angiographically identifiable thrombus: 43.1% versus 34.4%, P < .01; relative risk, 1,449; CI, 1.051 to 1.997. The absolute and relative losses were also higher in lesions containing angiographically identifiable thrombus (absolute loss, 0.43 +/- 0.66 versus 0.32 +/- 0.52; relative loss, 0.16 +/- 0.26 versus 0.13 +/- 0.21; both P < .05). The higher restenosis in these lesions was due primarily to an increased incidence of occlusion at follow-up angiography in this group: 13.8% versus 5.7%, P < .001. When lesions that went on to occlude by the time of follow-up angiography were excluded from the analysis, the restenosis rate between the two groups was similar by both the categorical (34.1% versus 30.4%, P=NS; relative risk, 1.183; CI, 0.824 to 1.696) and continuous (absolute loss, 0.23 +/- 0.46 versus 0.24 +/- 0.42, P=NS; relative loss, 0.09 +/- 0.17 versus 0.09 +/- 0.16, P=NS) approaches. CONCLUSIONS: Our results indicate that the presence of angiographically identifiable thrombus at the time of the angioplasty is associated with higher restenosis. The mechanism by which this occurs is through vessel occlusion at follow-up angiography. Measures aimed at improving outcome in this group of patients should be focused in this direction.     

Preventive effects of an antiallergic drug, pemirolast potassium, on restenosis after percutaneous transluminal coronary angioplasty

PURPOSE: Radiosurgery is an effective treatment for cerebral arteriovenous malformations. We conducted the present study to investigate the feasibility and efficacy of gamma knife radiosurgery for dural arteriovenous fistulas (DAVFs) of the cavernous sinus. METHODS: Eighteen patients (12 women and six men; 29-75 years old [mean age, 55 years]) with DAVFs of the cavernous sinus (Barrow's type B:1, C:7, and D:10) treated by gamma knife radiosurgery were enrolled in the study. DAVFs were bilateral in six patients and unilateral in 12. Stereotactic X-ray angiography and MR imaging were performed for targeting the radiosurgery. Areas of arteriovenous communication targeted for irradiation were first outlined on the X-ray angiograms. The target regions were then transferred to and displayed on the MR images. Dose planning was based on findings on the integrated images. Prescribed maximum target doses were 22 to 38 Gy (mean, 28 Gy). The targets were covered by 50% to 90% isodose levels. Radiation doses to the surrounding optic apparatus were kept to less than 8 Gy. The patients were followed up with color Doppler sonography and MR imaging. When noninvasive imaging suggested obliteration, X-ray angiography was performed to verify the results. RESULTS: The DAVFs were totally obliterated in 12 (80%) of the 15 patients. In the other three, one was almost completely obliterated at 14 months and two were partially obliterated at 19 and 27 months, respectively, after radiosurgery. No complications or symptom worsening occurred during the follow-up period. CONCLUSION: Gamma knife radiosurgery is a feasible, effective, and safe treatment for DAVFs of the cavernous sinus. Integration of stereotactic X-ray angiography and MR imaging not only aids treatment efficacy but also protects the relevant vital structures, especially the optic apparatus, from the hazards of radiation.     

Site-specific intracoronary heparin delivery in humans after balloon angioplasty. A radioisotopic assessment of regional pharmacokinetics

BACKGROUND: Demonstration and quantification of site-specific intracoronary administration of compounds has been confined thus far to the experimental animal laboratory. The aim of this study was to describe a scintigraphic method to demonstrate site-specific intracoronary drug delivery in humans. The methods allow on-line visualization and off-line quantification of site-specifically infused gamma-emitting compounds. METHODS AND RESULTS: In 12 patients after balloon angioplasty, 99mTc-labeled heparin was administered at the site of dilatation by use of a coil balloon. Both the infusion period and the washout period after the end of infusion were monitored with a gamma-camera. A curve of counts per pixel as a function of time was derived that showed an accumulation phase during infusion followed by washout phase after the end of infusion. Both phases were fitted by regression analysis and showed a linear accumulation pattern and a biexponential washout pattern. After correction for background counts, 99mTc decay, and body attenuation, peak heparin amount and regional bioavailability were calculated. Peak amount was defined as the initial point of the slow washout component of the biexponential curve (elimination component), and regional bioavailability was defined as the area under the curve of accumulation and washout phase. Half-life and retention time, define as seven half-lives, were obtained by use of the elimination component after correction for 99mTc decay. Mean peak delivered amount was 45 +/- 44 IU (236 +/- 228 micrograms), corresponding to an efficiency of delivery ranging from 1% to 8% of the totally infused dose. Total regionally bioavailable heparin reached 244 +/- 194 IU.h (1.28 +/- 1.01 mg.h). Retention time varied from 12 to 90 hours (mean, 50:33 +/- 22:50 hours:minutes). CONCLUSIONS: Site-specific intracoronary heparin delivery after angioplasty by means of the coil balloon was demonstrated in humans, and regional pharmacokinetics was quantified by use of a radioisotopic technique.     

Arterial remodeling after balloon angioplasty of the coronary artery: an intravascular ultrasound study. PICTURE Investigators. PostTreatment IntraCoronary Transluminal Ultrasound Result Evaluation

OBJECTIVE: Before balloon dilation, failure of compensatory enlargement and even arterial shrinkage are frequently observed at the lesion site in response to plaque accumulation. Balloon angioplasty may be regarded as artificial remodeling to enlarge the artery. The prevalence of the different types of arterial wall remodeling after applied stretch by balloon angioplasty is unknown. METHODS AND RESULTS: In 181 patients an intravascular ultrasound study was performed after coronary balloon angioplasty (n = 200 lesions). The vessel area was measured at a proximal and distal reference site and at the lesion site. Subsequently, the relative vessel area [(Vessel area lesion site)/Vessel area reference site) x 100] was calculated. Lesions were classified in three groups on the basis of their relative vessel areas: > or =105%, <105% but >95%, and < or =95%. A relative vessel area > or =105%, indicating enlargement compared with the reference site, was observed in 84 (44%) lesions. A relative vessel area <105% but >95% was observed in 43 (22%) lesions. A relative vessel area < or =95%, indicating "shrinkage" compared with the reference site, was observed in 66 (34%) lesions. CONCLUSIONS: After balloon angioplasty, the vessel area was found to be smaller compared with the reference site in 34% of the lesions. This small vessel area at the lesion site compared with a reference site may be a reflection of insufficient stretch by balloon angioplasty.     

Effect of the antioxidant Nicanartine on the proliferative and inflammatory response after experimental balloon angioplasty

BACKGROUND: Antioxidant treatment seems to reduce the development of restenosis after percutaneous transluminal angioplasty. In this study, the effect of Nicanartine, a new antioxidant drug with both antiproliferative and lipid-lowering properties, on the proliferative and inflammatory response after balloon angioplasty was investigated in a rabbit model of restenosis. METHODS: To induce pre-interventional plaques in the common carotid artery of 48 New Zealand White rabbits, electrostimulation was carried out for 28 days. After a break of 7 days, balloon angioplasty was performed in 36 animals, of which 18 received Nicanartine at a dose of 120 mg/kg body weight; the other 18 served as a control group. The vessels were excised by day 7 and 28 after balloon angioplasty and examined for intimal plaque size, macrophage content and proliferative activity. Bromodeoxyuridine labeling was used to determine proliferating cells in the dilated segment; macrophages were detected using the RAM-11 antibody. RESULTS: In the Nicanartine-treated group, immunohistological quantification 7 days after intervention showed a statistically significant (P< 0.05) reduction of both cells undergoing DNA synthesis (1.6+/-1.4% versus 3.7+/-2.2%) and intimal macrophages (0.7+/-1.2% versus 1.3+/-0.6%). Twenty-eight days after balloon angioplasty, proliferative activity in both groups was decreased to a level comparable to the non-dilated control groups. A clear trend towards smaller plaques could be seen in the Nicanartine group (0.146+/-0.077 mm2 versus 0.255+/-0.174 mm2). Total cholesterol levels did not differ significantly between the groups. CONCLUSION: Under treatment with Nicanartine a clear reduction in the proliferative and inflammatory response after balloon angioplasty was observed. Antioxidant treatment, especially with compounds having antiproliferative and lipid-lowering properties, appears to be an effective secondary preventive strategy after interventional treatment in patients with coronary artery disease.     

Comparative clinical and angiographic analysis of the initial efficacy and long-term follow-up of Wiktor stent implantation with conventional balloon angioplasty

This study was retrospectively designed to examine if the Wiktor stent, a balloon-expandable tantalum coil stent, provides a more favorable procedural and long-term clinical and angiographic outcome than does conventional coronary balloon angioplasty (POBA). From April 1995 to April 1996, we implanted 56 Wiktor stents in 46 lesions (LAD: 23, RCA: 16, CX: 7) in 42 patients (average age 53 +/- 10 years). Coronary lesions from the stent group were matched with similar lesions of another 42 POBA patients whose characteristics were identical to the Wiktor group. Revascularization indications in the Wiktor and POBA groups, respectively, were recent myocardial infarction (RMI) (45%, 40%), unstable (31%, 39%) and stable (24%, 21%) angina pectoris. 7% of the stents and 17% of the POBA balloons were less than 3 mm in diameter (p > 0.05). Procedural success was significantly greater in the Wiktor group than in the POBA group (100% vs. 92%, p < 0.05). Neither major cardiac event (death, CABG, acute myocardial infarction) nor (sub)acute occlusion was encountered in the Wiktor group during the hospitalization period and 1 month follow-up. There was 1 urgent CABG and 4 subacute occlusions in the POBA group. Control angiography at 8 months was performed in patients of both groups, of whom some were symptomatic at long-term follow-up or completely event free for 8 months. Angiographic restenosis (> 50% diameter stenosis) occurred in 25% of the Wiktor patients and in 43% of those in the POBA group (p < 0.05). For an 18 month clinical follow-up, 91% of the patients in the Wiktor group were asymptomatic and without ischemia in radionuclide imaging (RI), whereas 79% of the POBA patients were angina-free and 74% were without ischemia in the RI study. In conclusion, Wiktor stent implantation, with no major cardiac event or subacute occlusion, provides a more favorable procedural and long-term clinical and angiographic outcome than does conventional POBA.     

Effectiveness of an antioxidant in preventing restenosis after percutaneous transluminal coronary angioplasty: the Probucol Angioplasty Restenosis Trial

OBJECTIVES: The Probucol Angioplasty Restenosis Trial was a prospective, randomized, controlled study that investigated the effectiveness of probucol therapy in reducing the rate of restenosis after percutaneous transluminal coronary angioplasty (PTCA). BACKGROUND: Antioxidants have an inhibitory effect on smooth muscle cell growth in experiments in vitro and in vivo, which suggests a possible pharmacologic effect on restenosis after PTCA. METHODS: One hundred one patients were randomly assigned to receive 1,000 mg/day of probucol or control (no lipid-lowering) therapy 4 weeks before PTCA. After 4 weeks of premedication, both groups underwent PTCA. Probucol was continued until follow-up angiography 24 weeks after PTCA. Angiographic results were analyzed at a core laboratory by quantitative coronary angiography. RESULTS: Dilation was successful in 46 of 50 patients in the probucol group and 45 of 51 in the control group. At follow-up angiography 24 weeks after angioplasty, angiographic restenosis occurred in 9 (23%) of 40 patients in the probucol group and 22 (58%) of 38 in the control group (p = 0.001). Minimal lumen diameter was 1.49 +/- 0.75 mm (mean +/- SD) in the probucol group and 1.13 +/- 0.65 mm in the control group (p = 0.02). Percent diameter stenosis at follow-up angiography in the probucol group was significantly lower than that in the control group (43.9% vs. 56.4%, p = 0.009). The late loss was 0.37 +/- 0.69 mm in the probucol group and 0.60 +/- 0.62 mm in the control group (p = 0.13). The loss/gain ratio was 0.32 +/- 0.74 in the probucol group and 0.56 +/- 0.81 in the control group (p = 0.059). Net gain was greater in the probucol group than in the control group (0.77 +/- 0.70 vs. 0.48 +/- 0.59 mm, p = 0.053). CONCLUSIONS: Probucol administered beginning 4 weeks before PTCA appears to reduce restenosis rates.