Closure or medical therapy for cryptogenic stroke with patent foramen ovale.

BACKGROUND: The prevalence of patent foramen ovale among patients with cryptogenic stroke is higher than that in the general population. Closure with a percutaneous device is often recommended in such patients, but it is not known whether this intervention reduces the risk of recurrent stroke. METHODS: We conducted a multicenter, randomized, open-label trial of closure with a percutaneous device, as compared with medical therapy alone, in patients between 18 and 60 years of age who presented with a cryptogenic stroke or transient ischemic attack (TIA) and had a patent foramen ovale. The primary end point was a composite of stroke or transient ischemic attack during 2 years of follow-up, death from any cause during the first 30 days, or death from neurologic causes between 31 days and 2 years. RESULTS: A total of 909 patients were enrolled in the trial. The cumulative incidence (Kaplan-Meier estimate) of the primary end point was 5.5% in the closure group (447 patients) as compared with 6.8% in the medical-therapy group (462 patients) (adjusted hazard ratio, 0.78; 95% confidence interval, 0.45 to 1.35; P=0.37). The respective rates were 2.9% and 3.1% for stroke (P=0.79) and 3.1% and 4.1% for TIA (P=0.44). No deaths occurred by 30 days in either group, and there were no deaths from neurologic causes during the 2-year follow-up period. A cause other than paradoxical embolism was usually apparent in patients with recurrent neurologic events. CONCLUSIONS: In patients with cryptogenic stroke or TIA who had a patent foramen ovale, closure with a device did not offer a greater benefit than medical therapy alone for the prevention of recurrent stroke or TIA. (Funded by NMT Medical; ClinicalTrials.gov number, NCT00201461.).

Limericks for Myocardial Recovery and Regeneration.

Limericks are an easy, casual, and entertaining way to have fun with the English language. Creating them can be an engaging pastime to assist in memorizing important anatomic relationships necessary for being an interventional cardiologist or simply an intellectual exercise that provides respite after a hectic day in the cardiac catheterization laboratory, surgical suite, outpatient clinic, or intensive care unit. Interest in this form of poetry often dates back to when we, as children, were taught the simplistic rhyming pattern of a traditional limerick or learned one during adolescence. As we age, our limericks often became more humorous, personal, and bawdy. That evolution is the beauty of this poetic form. For this edition of Poet's Pen, we invited Dr. Marshall S. Flam, a noted dabbler in the limerick world, to pen "Limericks for Myocardial Recovery and Regeneration" to accompany the theme of this issue.

Low-dose sirolimus-eluting hydroxyapatite coating on stents does not increase platelet activation and adhesion ex vivo.

We previously found paclitaxel-eluting polymer-coated stents causing more human platelet-monocyte complex formation than bare metal stents in vitro. Presently, we examined patterns of platelet activation and adhesion after exposure to 6 nanofilm HAp-coated (HAp-nano) stents, 6 HAp-microporous-coated (HAp-micro) stents, 5 HAp sirolimus-eluting microporous-coated (HAp-SES) stents and 5 cobalt-chromium stents (BMS) deployed in an in vitro flow system. Blood obtained from healthy volunteers was circulated and sampled at 0, 10, 30 and 60 min. By flow cytometry, there were no significant differences in P-Selectin expression between the 4 stent types (HAp-nano = 32.5%; HAp-micro = 42.5%, HAp-SES = 10.23%, BMS = 7% change from baseline at 60 min, p = NS); PAC-1 antibody binding (HAp-nano = 11.8%; HAp-micro = 2.9%, HAp-SES = 18%, BMS = 6.4% change from baseline at 60 min, p = NS) or PMC formation (HAp-nano = 21.6%; HAp-micro = 4%, HAp-SES = 6.6%, BMS = 17.4% change from baseline at 60 min, p = NS). The 4 stent types did not differ in the average number of platelet clusters >10 µm in diameter by SEM (HAp-nano = 2.39 ± 5.75; HAp-micro = 2.26 ± 3.43; HAp-SES = 1.93 ± 3.24; BMS = 1.94 ± 2.41, p = NS). The majority of the struts in each stent group were only mildly covered by platelets, (HAp-nano = 80%, HAp-micro = 61%, HAp-SES = 78% and BMS = 52.1%, p = NS). The HAp-microporous-coated stents (ECD) attracted slightly more proteinaceous material than bare metal stents (HAp-micro = 35% struts with complete protein coverage, P < 0.0001 vs. other 3 stent types). In conclusion, biomimetic stent coating with nanofilm or microporous hydroxyapatite, even when eluting low-dose sirolimus, does not increase the platelet activation in circulating human blood, or platelet adhesion to stent surface when compared to bare metal stents in vitro.

Constantly Bombarded with New Drugs: What's a Cardiologist to Do?

Every physician encounters a barrage of direct-to-consumer and direct-to-physician advertising and is faced with the daunting task of deciding which drugs to add to their clinical armamentarium and how and when to add them. The purpose of this Points to Remember is to present a commonsense approach to incorporating newer drugs, or perhaps new indications for older drugs, into our clinical practice. To illustrate these points, this article focuses on a single drug, empagliflozin, a sodium-glucose cotransporter-2 (SGLT-2) inhibitor that has been highly marketed in lay and medical media and hence has been incorporated into professional society treatment guidelines.

Coenzyme Q10 for Patients With Cardiovascular Disease: JACC Focus Seminar.

Coenzyme Q10 (CoQ10) is a naturally occurring compound that is found in animals and all humans. It has a fundamental role in cellular energy production. Although it is produced in the body, tissue deficiency can occur due to medications such as statins, which inhibit the mevalonate pathway. The clinical syndromes of statin-associated muscle symptoms (SAMS) and some of the features observed in patients with heart failure (HF) may be related to blood and tissue deficiency of CoQ10. Numerous clinical trials of CoQ10 in SAMS have yielded conflicting results. Yet, the weight of evidence as reflected in meta-analyses supports the use of exogenous CoQ10 in SAMS. In patients with HF, large-scale randomized clinical trials are lacking, although one relatively contemporary trial, Q-SYMBIO, suggests an adjunctive role for CoQ10. The possibility that statin-related CoQ10 deficiency may play a role in patients with diastolic HF is an intriguing hypothesis that warrants further exploration.

Study design of the CLOSURE I Trial: a prospective, multicenter, randomized, controlled trial to evaluate the safety and efficacy of the STARFlex septal closure system versus best medical therapy in patients with stroke or transient ischemic attack due to presumed paradoxical embolism through a patent foramen ovale.

BACKGROUND AND PURPOSE: Some strokes of unknown etiology may be the result of a paradoxical embolism traversing through a nonfused foramen ovale (patent foramen ovale [PFO]). The utility of percutaneously placed devices for treatment of patients with cryptogenic stroke or transient ischemic attack (TIA) and PFO is unknown. In addition, there are no clear data about the utility of medical interventions or other surgical procedures in this situation. Despite limited data, many patients are being treated with PFO closure devices. Thus, there is a strong need for clinical trials that test the potential efficacy of PFO occlusive devices in this situation. To address this gap in medical knowledge, we designed the CLOSURE I trial, a randomized, clinical trial comparing the use of a percutaneously placed PFO occlusive device and best medical therapy versus best medical therapy alone for prevention of recurrent ischemic neurologic symptoms among persons with TIA or ischemic stroke. STUDY DESIGN: This prospective, multicenter, randomized, controlled trial has finished enrollment. Two-year follow-up for all 910 patients is required. The primary end point is the 2-year incidence of stroke or TIA, all-cause mortality for the first 30 days, and neurologic mortality from ≥ 31 days of follow-up, as adjudicated by a panel of physicians who are unaware of treatment allocation. This article describes the rationale and study design of CLOSURE I. CONCLUSIONS: This trial should provide information as to whether the STARFlex septal closure system is safe and more effective than best medical therapy alone in preventing recurrent stroke/TIA and mortality in patients with PFO and whether the STARFlex septal closure device can demonstrate superiority compared with best medical therapy alone. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00201461.

Coenzyme Q10.

Coenzyme Q10 (CoQ10) is among the most widely used dietary and nutritional supplements on the market. CoQ10 has several fundamental properties that may be beneficial in several clinical situations. This article reviews the pertinent chemical, metabolic, and physiologic properties of CoQ10 and the scientific data and clinical trials that address its use in two common clinical settings: statin-associated myopathy syndrome (SAMS) and congestive heart failure (CHF). Although clinical trials of CoQ10 in SAMS have conflicting conclusions, the weight of the evidence, as seen in meta-analyses, supports the use of CoQ10 in SAMS overall. In CHF, there is a lack of large-scale randomized clinical trial data regarding the use of statins in patients receiving contemporary treatment. However, one relatively recent randomized clinical trial, Q-SYMBIO, suggests an adjunctive role for CoQ10 in CHF. Recommendations regarding the use of CoQ10 in these clinical situations are presented.

Supplemental Vitamins and Minerals for Cardiovascular Disease Prevention and Treatment.

Vitamins and minerals are dietary supplements used by almost half of the US adult population based on the presumption that they help prevent or treat cardiovascular disease. Many studies, including randomized trials, have investigated the possible role of these substances in cardiovascular disease. We reviewed the available data on multivitamins/multiminerals, antioxidants, folic acid, vitamin E, niacin (B3), and beta-carotene. Despite extensive investigation, the evidence to date fails to support the use of exogenous supplements of vitamins and minerals for the prevention or treatment of cardiovascular disease. Here, we review some of the common supplements used by adults for cardiovascular health and the available evidence for risks/benefits.

Unmodified autologous stem cells at point of care for chronic myocardial infarction.

BACKGROUND: Numerous studies investigated cell-based therapies for myocardial infarction (MI). The conflicting results of these studies have established the need for developing innovative approaches for applying cell-based therapy for MI. Experimental studies on animal models demonstrated the potential of fresh, uncultured, unmodified, autologous adipose-derived regenerative cells (UA-ADRCs) for treating acute MI. In contrast, studies on the treatment of chronic MI (CMI; > 4 wk post-MI) with UA-ADRCs have not been published so far. Among several methods for delivering cells to the myocardium, retrograde delivery into a temporarily blocked coronary vein has recently been demonstrated as an effective option. AIM: To test the hypothesis that in experimentally-induced chronic myocardial infarction (CMI; > 4 wk post-MI) in pigs, retrograde delivery of fresh, uncultured, unmodified, autologous adipose-derived regenerative cells (UA-ADRCs) into a temporarily blocked coronary vein improves cardiac function and structure. METHODS: The left anterior descending (LAD) coronary artery of pigs was blocked for 180 min at time point T0. Then, either 18 × 106 UA-ADRCs prepared at "point of care" or saline as control were retrogradely delivered via an over-the-wire balloon catheter placed in the temporarily blocked LAD vein 4 wk after T0 (T1). Effects of cells or saline were assessed by cardiac magnetic resonance (CMR) imaging, late gadolinium enhancement CMR imaging, and post mortem histologic analysis 10 wk after T0 (T2). RESULTS: Unlike the delivery of saline, delivery of UA-ADRCs demonstrated statistically significant improvements in cardiac function and structure at T2 compared to T1 (all values given as mean ± SE): Increased mean LVEF (UA-ADRCs group: 34.3% ± 2.9% at T1 vs 40.4 ± 2.6% at T2, P = 0.037; saline group: 37.8% ± 2.6% at T1 vs 36.2% ± 2.4% at T2, P > 0.999), increased mean cardiac output (UA-ADRCs group: 2.7 ± 0.2 L/min at T1 vs 3.8 ± 0.2 L/min at T2, P = 0.002; saline group: 3.4 ± 0.3 L/min at T1 vs 3.6 ± 0.3 L/min at T2, P = 0.798), increased mean mass of the left ventricle (UA-ADRCs group: 55.3 ± 5.0 g at T1 vs 71.3 ± 4.5 g at T2, P < 0.001; saline group: 63.2 ± 3.4 g at T1 vs 68.4 ± 4.0 g at T2, P = 0.321) and reduced mean relative amount of scar volume of the left ventricular wall (UA-ADRCs group: 20.9% ± 2.3% at T1 vs 16.6% ± 1.2% at T2, P = 0.042; saline group: 17.6% ± 1.4% at T1 vs 22.7% ± 1.8% at T2, P = 0.022). CONCLUSION: Retrograde cell delivery of UA-ADRCs in a porcine model for the study of CMI significantly improved myocardial function, increased myocardial mass and reduced the formation of scar tissue.

In vivo plaque characterization using intravascular ultrasound-virtual histology in a porcine model of complex coronary lesions.

OBJECTIVE: To determine the accuracy of detection of different tissue types of intravascular ultrasound-virtual histology (IVUS-VH) in a porcine model of complex coronary lesions. METHODS AND RESULTS: Coronary lesions were induced by injecting liposomes containing human oxidized low-density lipoprotein into the adventitia of the arteries. IVUS-VH imaging was performed in vivo at 8.2+/-1.6 weeks after injection. A total of 60 vascular lesions were analyzed and compared with their correspondent IVUS-VH images. Correlation analysis was performed using linear regression models. Compared with histology, IVUS-VH correctly identified the presence of fibrous, fibro-fatty, and necrotic tissue in 58.33%, 38.33%, and 38.33% of lesions, respectively. The sensitivity of IVUS-VH for the detection of fibrous, fibro-fatty, and necrotic core tissue was 76.1%, 46%, and 41.1% respectively. A linear regression analysis performed for each individual plaque component did not show strong correlation that would allow significant prediction of individual values. CONCLUSIONS: In a porcine model of complex coronary lesions, IVUS-VH was not accurate in detecting the relative amount of specific plaque components within each individual corresponding histological specimen.

A paclitaxel-eluting stent for the prevention of coronary restenosis.

BACKGROUND: Intimal hyperplasia and resulting restenosis limit the efficacy of coronary stenting. We studied a coronary stent coated with the antiproliferative agent paclitaxel as a means of preventing restenosis. METHODS: We conducted a multicenter, randomized, controlled, triple-blind study to evaluate the ability of a paclitaxel-eluting stent to inhibit restenosis. At three centers, 177 patients with discrete coronary lesions (<15 mm in length, 2.25 to 3.5 mm in diameter) underwent implantation of paclitaxel-eluting stents (low dose, 1.3 microg per square millimeter, or high dose, 3.1 microg per square millimeter) or control stents. Antiplatelet therapies included aspirin with ticlopidine (120 patients), clopidogrel (18 patients), or cilostazol (37 patients). Clinical follow-up was performed at one month and four to six months, and angiographic follow-up at four to six months. RESULTS: Technical success was achieved in 99 percent of the patients (176 of 177). At follow-up, the high-dose group, as compared with the control group, had significantly better results for the degree of stenosis (mean [+/-SD], 14+/-21 percent vs. 39+/-27 percent; P<0.001), late loss of luminal diameter (0.29+/-0.72 mm vs. 1.04+/-0.83 mm, P<0.001), and restenosis of more than 50 percent (4 percent vs. 27 percent, P<0.001). Intravascular ultrasound analysis demonstrated a dose-dependent reduction in the volume of intimal hyperplasia (31, 18, and 13 mm3, in the high-dose, low-dose, and control groups, respectively). There was a higher rate of major cardiac events in patients receiving cilostazol than in those receiving ticlopidine or clopidogrel. Among patients receiving ticlopidine or clopidogrel, event-free survival was 98 percent and 100 percent in the high-dose and control groups, respectively, at one month, and 96 percent in both at four to six months. CONCLUSIONS: Paclitaxel-eluting stents used with conventional antiplatelet therapy effectively inhibit restenosis and neointimal hyperplasia, with a safety profile similar to that of standard stents.

Safety of sirolimus-eluting stenting and its effect on restenosis in patients with unstable angina pectoris (a SIRIUS substudy).

The SIRIUS study was a double-blinded, randomized trial of the sirolimus-eluting stent (SES) to evaluate its effect on the rate of restenosis. The present report is a retrospective analysis of short- and long-term outcomes of SESs compared with bare metal stents (BMSs) in a subgroup of patients with unstable angina enrolled in the trial. Of 1,058 patients randomized in SIRIUS, 533 (50.4%) had unstable angina pectoris and 490 had stable angina. In the unstable angina group, patients treated with SESs and BMSs had similar clinical and angiographic characteristics. The stenting procedure was highly successful in the 2 groups (95.9% and 97.4%, respectively) with similar immediate angiographic results and short-term (in-hospital) clinical event rates. At 1-year follow-up, compared with BMSs, patients with unstable angina treated with SESs had significantly lower rates of target lesion revascularization (5.5% vs 22.3%, p <0.0001), target vessel failure (10.9% vs 26.3%, p <0.0001), and major adverse cardiac events (8.4% vs 24.8%, p <0.0001). Stent thrombosis was a rare event, with only 1 patient (0.4%) in each group during the first 30 days. Late thrombosis occurred in 2 patients (0.7%) in the BMS group but in none of the SES group. In conclusion, in the higher risk subgroup of patients with unstable angina, SESs are as safe as BMSs in decreasing restenosis and the need for repeat revascularization. This is reflected by a significant decrease in major adverse cardiac events and target vessel failure. Patients with unstable angina undergoing percutaneous coronary intervention who meet the entry criteria of the SIRIUS study should be preferentially treated with SESs.

Outcomes with the polymer-based paclitaxel-eluting TAXUS stent in patients with diabetes mellitus: the TAXUS-IV trial.

OBJECTIVES: We sought to determine the safety and efficacy of polymer-regulated site-specific delivery of paclitaxel in patients with diabetes mellitus undergoing stent implantation. BACKGROUND: Percutaneous coronary intervention in patients with diabetes is associated with high rates of restenosis and repeat revascularization due to excessive neointimal proliferation, a process that may be blunted with the site-specific delivery of paclitaxel. METHODS: In the TAXUS-IV trial, 1,314 patients were prospectively randomized to the slow rate-release polymer-based paclitaxel-eluting TAXUS stent or the bare-metal EXPRESS stent (Boston Scientific Corp., Natick, Massachusetts). Medically treated diabetes was present in 318 patients (24%), 105 of whom required insulin. RESULTS: Among patients with diabetes, the TAXUS stent, compared to the bare-metal stent, reduced the rate of 9-month binary angiographic restenosis by 81% (6.4% vs. 34.5%, p < 0.0001), and reduced the 12-month rates of target lesion revascularization by 65% (7.4% vs. 20.9%, p = 0.0008), target vessel revascularization by 53% (11.3% vs. 24%, p < 0.004), and composite major adverse cardiac events by 44% (15.6% vs. 27.7%, p = 0.01). The one-year rates of cardiac death (1.9% vs. 2.5%), myocardial infarction (3.2% vs. 6.4%), and subacute thrombosis (0.6% vs. 1.2%) were comparable between the paclitaxel-eluting and control stents, respectively. In the insulin-requiring subgroup, the TAXUS stent reduced angiographic restenosis by 82% (7.7% vs. 42.9%, p = 0.0065), and reduced the one-year rate of target lesion revascularization by 68% (6.2% vs. 19.4%, p = 0.07), a relative reduction similar to patients without diabetes. CONCLUSIONS: The site-specific delivery of paclitaxel after coronary stent implantation is highly effective in reducing clinical and angiographic restenosis in patients with diabetes mellitus.

Comparison of the efficacy of direct coronary stenting with sirolimus-eluting stents versus stenting with predilation by intravascular ultrasound imaging (from the DIRECT trial).

A direct coronary stenting technique using drug-eluting stents may decrease drug-eluting stent efficacy due to possible damage to the surface coating of the stent. The DIRECT is a multicenter, prospective, nonrandomized trial designed to evaluate the direct stenting strategy for the sirolimus-eluting Bx-Velocity stent compared with the historical control (SIRIUS trial, stenting with predilation). Volumetric and cross-sectional intravascular ultrasound analyses at 8-month follow-up were performed in 115 patients (DIRECT n= 64, control n = 51). Patient and lesion characteristics were comparable between groups. The DIRECT group achieved an equivalent uniform expansion index, defined as minimum stent area/maximum stent area x 100, compared with the control group (65.9 +/- 11.7 vs 63.1 +/- 12.7, p = NS). At 8-month follow-up, vessel, stent, lumen, and neointimal volume index (volume in cubic millimeters/length in millimeters) and percent neointimal volume were similar between the DIRECT and control groups (vessel volume index 13.9 +/- 4.40 vs 15.0 +/- 3.83; stent volume index 6.83 +/- 2.02 vs 6.94 +/- 2.04; lumen volume index 6.71 +/- 2.04 vs 6.81 +/- 2.07; neointimal volume index 0.14 +/- 0.24 vs 0.16 +/- 0.23; percent neointimal volume 3.73 +/- 6.97 vs 3.14 +/- 5.32, p = NS for all). In addition, in-stent neointimal hyperplasia distribution was significantly smaller near the distal stent edge (0.22 vs 0.098 mm(3)/mm, p = 0.01 for an average neointimal volume index within 3 mm from the distal stent edge). In conclusion, direct coronary stenting with the sirolimus-eluting Bx-Velocity stent is equally effective in terms of uniform stent expansion and long-term quantitative intravascular ultrasound results compared with conventional stenting using predilation. This strategy appears to be associated with less neointimal hyperplasia near the distal stent edge.

Single perivascular delivery of mitomycin C stimulates p21 expression and inhibits neointima formation in rat arteries.

OBJECTIVE: Mitomycin C (MMc) is an antibiotic that exerts a potent antiproliferative effect in tumor cells. Because the proliferation of vascular smooth muscle cells (VSMCs) plays a prominent role in the development of restenosis after percutaneous coronary interventions, the present study examined the effect of MMc on VSMC proliferation and on neointima formation after arterial balloon injury. METHODS AND RESULTS: Treatment of cultured rat aortic VSMCs with MMc (1 nmol to 30 micromol/L) inhibited VSMC proliferation in a concentration-dependent manner. Whereas high concentrations of MMc (1 to 30 micromol/L) induced VSMC apoptosis, as reflected by DNA laddering and caspase-3 activation, lower concentrations of MMc (1 to 300 nmol/L) directly inhibited VSMC growth by arresting cells in the G2/M phase of the cell cycle. The antiproliferative action of MMc was associated with a selective increase in the expression of the cyclin-dependent kinase inhibitor p21, and with a decrease in cyclin B1-cyclin-dependent kinase-1 complex activity. Finally, the local perivascular delivery of MMc immediately after balloon injury of rat carotid arteries induced p21 expression and markedly attenuated neointima formation. CONCLUSIONS: These studies demonstrate that MMc exerts a potent inhibitory effect on VSMC proliferation and neointima formation after arterial injury. MMc represents a potentially new therapeutic agent in treating and preventing vasculoproliferative disease.

Initial impact of drug-eluting stent use on the spectrum of patients undergoing percutaneous coronary intervention.

BACKGROUND: The availability of drug-eluting stents was expected to expand the application of percutaneous coronary intervention to a wider group of patients and lesion types. We sought to determine whether drug-eluting stents' availability has changed the practices of operators performing percutaneous coronary intervention with regard to patient selection and procedural factors. METHODS: We compared the clinical and angiographic characteristics of patients who underwent percutaneous coronary intervention at the Methodist Hospital, Houston, Texas, during three periods: June 2002-March 2003, June 2003-March 2004 and June 2004-March 2005. Sirolimus-eluting stents were available during the latter two periods. Paclitaxel eluting stents became available during the third period. RESULTS: A greater proportion of patients undergoing diagnostic catheterization were referred for percutaneous coronary intervention during the latter two periods (26.8%, 30.4%, 30.4%, respectively, P<0.0001). Patients undergoing stent placement during the latter two periods were more likely to have hypertension, hyperlipidemia or to have undergone previous percutaneous coronary intervention. The average implanted stent length was greater during the latter periods (14.5+/-4.6, 16.4+/-5.2, 16.8+/-5.5 mm, respectively, P<0.0001) and the average stent diameter was smaller (3.23+/-1.22, 3.13+/-1.16, 3.02+/-0.6 mm, respectively, P<0.0001). The frequency of percutaneous coronary intervention involving long lesions (>20 mm) and Left Anterior Descending (LAD) lesions was higher in the latter two periods and the frequency of multivessel stenting was higher in the last period. CONCLUSIONS: The spectrum of patients and coronary lesions that have undergone stenting has changed, particularly in the third period when both drug-eluting stent types were available. We observed a gradual shift toward higher-risk clinical and lesion characteristics following the introduction of drug-eluting stents.

Inhibition of restenosis with a paclitaxel-eluting, polymer-free coronary stent: the European evaLUation of pacliTaxel Eluting Stent (ELUTES) trial.

BACKGROUND: The use of a stent to deliver a drug may reduce in-stent restenosis. Paclitaxel interrupts the smooth muscle cell cycle by stabilizing microtubules, thereby arresting mitosis. METHODS AND RESULTS: On the basis of prior animal studies, the European evaLUation of the pacliTaxel Eluting Stent (ELUTES) pilot clinical trial (n=190) investigated the safety and efficacy of V-Flex Plus coronary stents (Cook Inc) coated with escalating doses of paclitaxel (0.2, 0.7, 1.4, and 2.7 microg/mm2 stent surface area) applied directly to the abluminal surface of the stent in de novo lesions compared with bare stent alone. The primary efficacy end point was angiographic percent diameter stenosis at 6 months. At angiographic follow-up, percent diameter stenosis was 33.9+/-26.7% in controls (n=34) and 14.2+/-16.6% in the 2.7-microg/mm2 group (n=31; P=0.006). Late loss decreased from 0.73+/-0.73 to 0.11+/-0.50 mm (P=0.002). Binary restenosis (> or =50% at follow-up) decreased from 20.6% to 3.2% (P=0.056), with no significant benefit from intermediate paclitaxel doses. Freedom from major adverse cardiac events in the highest (effective) dose group was 92%, 89%, and 86% at 1, 6, and 12 months, respectively (P=NS versus control). No late stent thromboses were seen in any treated group despite clopidogrel treatment for 3 months only. CONCLUSIONS: Paclitaxel applied directly to the abluminal surface of a bare metal coronary stent, at a dose density of 2.7 microg/mm2, reduced angiographic indicators of in-stent restenosis without short- or medium-term side effects.

Intravascular ultrasound assessment of neointima distribution and the length of stent that was free of intravascular ultrasound-detectable intimal hyperplasia in paclitaxel-eluting stents.

Using data from the ASian Paclitaxel-Eluting Stent Clinical Trial, a 3-center, randomized, placebo-controlled trial of nonpolymeric paclitaxel-coated stents with a single center, 81-patient intravascular ultrasound (IVUS) substudy, the length of a stent that was free of IVUS-detectable intimal hyperplasia measured 3.2 +/- 4.8 mm in placebo stents, 6.1 +/- 5.6 mm in low-dose stents, and 8.7 +/- 6.1 mm in high-dose stents (p = 0.0029). IVUS percent neointima volume obstruction correlated with the length of this IVUS neointima-free segment (r = 0.785, p <0.0001); angiographic late lumen loss and follow-up diameter stenosis also correlated with the IVUS neointima-free length of the stents (r = 0.670, p <0.0001 and r = 0.679, p <0.0001, respectively.

Comparison of quantitative angiographic parameters with the magnitude of neointimal hyperplasia measured by volumetric intravascular ultrasound in patients treated with bare metal and nonpolymeric paclitaxel-coated stents.

We used data from the ASian Paclitaxel-Eluting Stent Clinical Trial (a 3-center, randomized, placebo-controlled trial of nonpolymeric paclitaxel-coated stents with a single-center intravascular ultrasound substudy) to compare angiographic indexes of drug-eluting stent efficacy with the magnitude of intimal hyperplasia (IH) assessed by intravascular ultrasound. Overall, percent IH (IH volume divided by stent volume) was larger in restenotic lesions than in nonrestenotic lesions (46 +/- 19% vs 15 +/- 13%, p <0.0001); angiographic late loss and follow-up diameter stenoses correlated strongly with percent IH.