Long-term follow-up of the randomised controlled trial to evaluate the safety and efficacy of the zotarolimus-eluting driver coronary stent in de novo native coronary artery lesions: five year outcomes in the ENDEAVOR II study.

AIMS: We report here the final 5-year follow-up results from the ENDEAVOR II trial, which was the first randomised trial evaluating the Endeavor(tm) zotarolimus-eluting stent (ZES) compared with a bare metal stent (BMS) in patients with single, de novo coronary artery lesions. METHODS AND RESULTS: Eligible patients were randomised 1:1 to receive ZES or BMS and were followed by telephone or clinic visit up to five years. We evaluated TVF and its components (target vessel revascularisation [TVR], Q-wave or non Q-wave myocardial infarction, or cardiac death attributed to the target vessel) at five years. Additionally, we report rates of MACE, TLR, and stent thrombosis (protocol- and ARC-defined) through five years. ENDEAVOR II enrolled 1,197 patients (598 ZES, 599 BMS). At five years of follow-up, the rates of TVF (15.4% vs 24.4%), TVR (10.7% vs 20.1%), MACE (15.4% vs 24.6%), and TLR (7.5% vs 16.3%) remained significantly lower in ZES patients compared with BMS patients. ARC definite and probable very late (>1 year) stent thrombosis remained low (0.2% ZES and 0.3% BMS) through five years. CONCLUSIONS: After five years of follow-up, ZES demonstrated significantly improved clinical outcomes with sustained safety compared with BMS in patients with obstructive coronary artery disease.

StentBoost used to guide management of a critical ostial right coronary artery lesion.

This report describes a case of a critical ostial lesion of a dominant right coronary artery (RCA) in a patient with poor left ventricular function due to a previous anterior infarction and documented late drug-eluting stent thrombosis of the RCA. The precise non-invasive determination of the proximal edge of a previously deployed stent by a new imaging technique, StentBoost, showed the lesion not only to be proximal to the stent in the uncovered ostium, but also restricted to the section outside the stent. This, together with the patient's clinical factors, suggested that stent placement was the optimal treatment strategy.

Primary percutaneous coronary intervention in saphenous vein grafts: a visualization strategy to improve outcome with new uses for the aspiration catheter.

Primary percutaneous coronary intervention (PCI) of saphenous vein grafts (SVG) is often a high-risk procedure associated with poor short- and long-term outcomes. Venous grafts frequently supply a clinically important myocardial territory. These vessels, however, combine the problems of a less predictable course and run-off as compared to native vessels with the presence of severe degenerative atherosclerosis. These factors amplify the risk due to an increased chance of distal embolization and no-reflow. We present three different situations during primary PCI in SVGs where a thrombosuction catheter was utilized to visualize the problem and then apply therapeutic maneuvers that proved crucial in achieving a successful result.

Overview of the transradial approach in percutaneous coronary intervention.

Thirteen years have passed since the first percutaneous coronary intervention was performed at Onze Lieve Vrouwe Gasthuis in Amsterdam using the transradial approach (TRA). Since then TRA has spread through the interventional community and many centres have now adopted TRA as the arterial access of choice. This review is focused on the hot issues and the latest developments in this field. The following subjects will be addressed and discussed: drawbacks and learning curve, procedural technique, indications (with particular attention to acute coronary patients), complications, contraindications, nurse workload, patient management, and economics.

Randomized, double-blind, multicenter study of the Endeavor zotarolimus-eluting phosphorylcholine-encapsulated stent for treatment of native coronary artery lesions: clinical and angiographic results of the ENDEAVOR II trial.

BACKGROUND: The use of the Endeavor stent might reduce restenosis and stent thrombosis at 9 months. METHODS AND RESULTS: Patients (n = 1197) treated for single coronary artery stenosis were enrolled in a prospective, randomized, double-blind study and randomly assigned to receive the Endeavor zotarolimus-eluting phosphorylcholine polymer-coated stent (n = 598) or the same bare metal stent but without the drug or the polymer coating (n = 599). The 2 groups were well matched in baseline characteristics. Diabetes was present in 20.1% of patients; the mean reference vessel diameter was 2.75 mm; and the mean lesion length was 14.2 mm. The primary end point of target vessel failure at 9 months was reduced from 15.1% with the bare metal stent to 7.9% with the Endeavor (P = 0.0001), and the rate of major adverse cardiac events was reduced from 14.4% with the bare metal stent to 7.3% with the Endeavor (P = 0.0001). Target lesion revascularization was 4.6% with Endeavor compared with 11.8% with the bare metal stent (P = 0.0001). The rate of stent thrombosis was 0.5% with the Endeavor, which was not significantly different from 1.2% with the bare metal stent. In 531 patients submitted to angiographic follow-up, late loss was reduced from 1.03 +/- 0.58 to 0.61 +/- 0.46 (P < 0.001) in stent and from 0.72 +/- 0.61 to 0.36 +/- 0.46 (P < 0.001) in segment. The rate of in-segment restenosis was reduced from 35.0% to 13.2% with Endeavor (P < 0.0001). There was no excessive edge stenosis, aneurysm formation, or late acquired malapposition by intravascular ultrasound imaging. Differences in clinical outcome were maintained at 12 and 24 months (P < 0.0001). CONCLUSIONS: Compared with bare metal stents, the Endeavor stent is safe and reduces the rates of clinical and angiographic restenosis at 9, 12, and 24 months.

NT-ProBNP serum levels reflect severity and extent of ischemia in patients admitted with non-ST-elevation acute coronary syndrome.

OBJECTIVE: To explore the relationship between NT-proBNP elevation and prognosis in patients with NSTEACS. BACKGROUND: High NT-proBNP levels are related to a worse prognosis in patients with ACS. The precise mechanism by which is not clear. METHODS: Serial sampling of NT-proBNP, Troponin T and CK-MB was performed in 23 patients admitted with NSTEACS. Using coronary angiography in each patient a culprit lesion was identified. Proximal lesions were located before or at the first major branch of the parent artery. All other lesions localizations were considered distal. To evaluate the influence of left ventricular systolic function on NT-proBNP levels WMSI was measured by echocardiography. RESULTS: Proximal culprit lesion localization was associated with significant higher baseline (mean 506 ng/l, SD 440 ng/l) and peak NT-proBNP levels (mean 1055 ng/l; SD 236 ng/l), as compared to patients with a distal lesion localization. (Baseline: 139 ng/l, SD 140 ng/l, peak: 381 ng/l; SD 64 ng/l). (P = 0.01) NT-proBNP levels were highly correlated to Troponin T and CK-MB peak serum levels. Adjustments for left ventricular dysfunction did not alter these associations. CONCLUSIONS: High peak NT-proBNP levels are independently associated with both proximal culprit localization and elevated biochemical markers of myocardial damage. These findings suggest that NT-proBNP levels reflect the amount of jeopardized myocardium and could signify the integral of the extent and severity of an ischemic event.

Oral administration of glycine in the prevention of restenosis after coronary angioplasty. A double blind placebo controlled randomized feasibility trial evaluating safety and efficacy of glycine in the prevention of restenosis after angioplasty.

OBJECTIVES: Evaluation of safety, feasibility, and efficacy of oral administered glycine in prevention of angiographic restenosis six months after percutaneous coronary intervention (PCI). BACKGROUND: The amino acid glycine modulates immunological response and enhances the production of endothelial derived nitric oxide (EDNO) factor. This factor has been shown to possess anti-atherosclerotic properties, actions of which are thought to reduce neo-intimal hyperplasia. Furthermore, glycine significantly elevates arginine serum levels. This amino acid has been extensively studied for its effects on the endothelium, nitric oxide (NO) metabolism and effects on several biochemical pathways interfering with the process of restenosis after PCI. METHODS: A prospective double blind placebo controlled randomized study evaluated safety and feasibility of chronic oral administration of glycine. In addition, the efficacy was determined by evaluation of six months angiographic restenosis rates. RESULTS: 214 patients scheduled for elective PCI were randomized to receive glycine or placebo. At follow-up, there was no significant difference in side effects and in major adverse cardiac events (MACE) between both groups. Six-month angiograms revealed similar restenosis rates for the glycine group (17.5%) and for the placebo group (20.2%) (P = 0.82). CONCLUSION: Chronic oral administration of glycine was safe and feasible and had similar side effects compared to placebo. However, chronic oral administration of glycine did not lead to a significant reduction in restenosis rates at six months after elective PCI.

Dynamics in N-terminal pro-brain natriuretic peptide concentration in patients with non-ST-elevation acute coronary syndrome.

BACKGROUND: Although there is growing evidence that N-terminal pro-brain natriuretic peptide (NT-proBNP) can be used as a powerful tool in risk prediction in patients with non-ST-elevation acute coronary syndrome (NSTEACS), the dynamic variation of serum concentrations in time is poorly understood. To gain insight into the dynamics of NT-proBNP, a study was performed using serial serum samples in patients admitted with NSTEACS. METHODS: A total of 24 patients admitted with NSTEACS was included in this study. Serial samples were taken at baseline, 8 hours, 16 hours, 24 hours, and 36 hours after admittance. RESULTS: A highly dynamic pattern in serial measurements of NT-proBNP was observed. Although an increase in NT-proBNP serum levels already existed 8 hours after admittance, it did not reach significance as compared with baseline. The samples obtained 16, 24, and 36 hours after admission were all significantly increased as compared with the values at admission (P < .01), generally leading to a > 2-fold increase with peak values at 16 to 24 hours after admittance. Furthermore, considerable differences in NT-proBNP concentrations between patients were observed. CONCLUSIONS: It was shown that NT-proBNP is a highly dynamic cardiac peptide. Strategic sampling at 16 to 24 hours after admittance could prove representative regarding the assessment of risk prediction and subsequent clinical decision making.

Early discharge is feasible following primary percutaneous coronary intervention with transradial stent implantation under platelet glycoprotein IIb/IIIa receptor blockade. Results of the AGGRASTENT Trial.

BACKGROUND: Primary percutaneous coronary intervention (PCI) with stent implantation demonstrated to be superior to both PCI with balloon angioplasty and to thrombolysis for acute ST-elevation myocardial infarction (STEMI). The use of glycoprotein (GP) IIb-IIIa blockers in this setting may be beneficial. However, GP IIb-IIIa receptor blocker treatment is frequently accompanied by femoral entry site-related bleeding complications, resulting in additional morbidity and prolonged hospitalization. These complications are minimized by using the transradial approach (TRA). METHODS: This study prospectively explored the feasibility of early discharge (within 4 days) following primary PCI with transradial stent implantation under GP IIb-IIIa blockade with tirofiban in the setting of STEMI. One-hundred patients with STEMI eligible for PCI were included. RESULTS: Of these 100 patients, 62% received treatment according to the protocol, e.g., TRA, successful PCI with stent implantation, full-dose GP IIb/IIIa receptor blocker infusion and early discharge. The PCI was successful in 95%. Early discharge was achieved in 75 patients of the total study population. Major adverse cardiac and cerebral events (MACCE) did not occur in the early discharge group, with a 1-year event-free survival rate of 91%. The combined MACCE rates in the total study population at 1, 6, and 12 months were 8%, 15% and 20%, respectively. CONCLUSION: Early discharge is feasible following primary PCI with stent implantation via the radial artery under GP IIb-IIIa blockade for STEMI, however a larger study is needed to prove the efficacy of this strategy.

Outpatient coronary angioplasty: feasible and safe.

This study tested the safety and feasibility of coronary angioplasty on an outpatient basis. The purpose of this approach includes cost-effectiveness and patient comfort. Six hundred forty-four patients were randomized to either transradial or transfemoral PTCA using 6 Fr equipment. Patients were triaged to outpatient management based on a predefined set of predictors of an adverse outcome in the first 24 hr after initially successful coronary angioplasty. Three hundred seventy-five patients (58%) were discharged 4-6 hr after PTCA; 42% stayed in hospital overnight. In the outpatient group, one adverse event occurred (subacute stent thrombosis 7 hr postdischarge, nonfatal myocardial infarction). There were no major vascular complications. In the hospital group, 19 patients (7%) sustained an adverse cardiac even in the first 24 hr; 1 patient died. Patients treated via the femoral route had more (minor) bleeding complications (19 patients; 6%); in 17 of these, this was the sole reason that discharge was delayed. PTCA on an outpatient basis, performed via the radial or the femoral artery with low-profile equipment, is safe and feasible in a considerable part of a routine PTCA population. A larger proportion of transradial patients can be discharged due to a reduction in (minor) bleeding complications.

Maintenance of long-term clinical benefit with sirolimus-eluting coronary stents: three-year results of the RAVEL trial.

BACKGROUND: The use of sirolimus-eluting coronary stents has been associated with a nearly complete elimination of restenosis at 6 months and with a very low 1-year incidence of major adverse cardiac events (MACE). This analysis examined whether these beneficial effects persist over the longer term. METHODS AND RESULTS: This multicenter trial randomly assigned 238 patients to revascularization of single, de novo, native coronary artery lesions with sirolimus-eluting versus conventional bare-metal stents. Survival free from target lesion revascularization (TLR), target vessel failure (TVF), and MACE up to 3 years of follow-up was compared between the 2 treatment groups. Complete data sets were available in 94.2% of patients treated with sirolimus-eluting stents and in 94.1% of patients randomized to the control group. The cumulative 1-, 2-, and 3-year event-free survival rates were 99.2%, 96.5%, and 93.7% for TLR and 95.8%, 92.3%, and 87.9% for TVF, respectively, in the sirolimus-eluting stent group, versus 75.9%, 75.9%, and 75.0% for TLR and 71.2%, 69.4%, and 67.3% for TVF in the control group (P<0.001 for both comparisons at 3 years). Rates of MACE at 3 years were 15.8% in patients randomly assigned to sirolimus-eluting stents versus 33.1% in patients assigned to bare-metal stents (P=0.002). One patient treated with a sirolimus-eluting stent died of a cardiac cause between 12 and 36 months. CONCLUSIONS: Treatment of de novo coronary stenosis with sirolimus-eluting stents was associated with a sustained clinical benefit and very low rates of TLR and of other MACE up to 3 years after device implantation.

Lack of efficacy of clopidogrel pre-treatment in the prevention of myocardial damage after elective stent implantation.

OBJECTIVES: The object of this study was to determine the effect of pre-treatment with clopidogrel in patients undergoing elective stent implantation. BACKGROUND: The treatment of patients with adenosine diphosphate receptor blockers after percutaneous coronary intervention (PCI) with stent implantation has been shown to decrease the incidence of subacute stent thrombosis. Furthermore, non-randomized studies on pre-treatment with clopidogrel among patients undergoing stent implantation have suggested a reduction in myocardial damage and clinical events. The effect of pre-treatment with clopidogrel has been studied in only a few randomized trials. METHODS: In a randomized trial, three days of pre-treatment with clopidogrel was compared with standard post-procedural treatment in 203 patients undergoing elective stent implantation. The primary end point was a rise in troponin I or creatine kinase-MB fraction (CK-MB) serum levels at 6 to 8 and 16 to 24 h after PCI. Secondary end points were death, stroke, myocardial infarction, coronary bypass grafting, repeated PCI, and subacute stent thrombosis at one and six months after PCI. RESULTS: No difference was found between non-pre-treated and pre-treated patients in the post-procedural elevation of troponin I (42 [43.3%] vs. 48 [51.1%], respectively, p = 0.31) or CK-MB (6 [6.3%] vs. 7 [7.4%], respectively, p = 0.78). Adjustment for possible confounding factors did not change these findings. Patient follow-up at one and six months showed no significant difference between the treatment groups in death, stroke, myocardial infarction, coronary artery bypass grafting, repeated PCI, or subacute stent thrombosis. CONCLUSIONS: In this randomized study, no beneficial effect of pre-treatment with clopidogrel on post-procedural elevation of troponin I and CK-MB or on clinical events after one and sixth months could be demonstrated. The study suggests that among patients with stable coronary syndromes in whom coronary stent implantation is planned, pre-treatment may not be beneficial in reducing early myocardial damage.

A prospective multicentre registry of the procedural and long-term clinical and angiographic results of stent implantation using a Dylyn coated coronary stent system.

OBJECTIVES: A prospective registry was performed to evaluate the safety and efficacy of a Dylyn coated coronary stent. BACKGROUND: Diamond-like nanocomposite (Dylyn) stent coating is thought to be biocompatible, resulting in decreased thrombogenicity and decreased neointimal hyperplasia. METHODS: In a multicentre, open, prospective, clinical and angiographical registry, the Dylyn-coated stent system was evaluated in patients requiring percutaneous coronary intervention. The primary procedural and angiographical endpoint of the study was the sustained success of stent-implantation using a follow-up catheterisation at six months. The primary clinical endpoint of the study was the composite incidence of death, non-fatal myocardial infarction and revascularisation at six months after stent implantation. RESULTS: 127 Dylyn coated coronary stents were implanted in 121 patients. Procedural success was obtained in 100% of the cases. No episodes of acute stent thrombosis occurred. The number of patients within stent restenosis at six months was 29 (24%). The primary procedural, angiographical endpoint was achieved in 91 (70%) patients. The clinical results at six-month follow-up were favourable with a MACE-rate of 7.4%. CONCLUSIONS: A Dylyn coated coronary stent system is well tolerated and has excellent short-term results. The amount of angiographic restenosis at 6 months, however, is considerable, but comparable to other non-drug-eluting stent systems.

Early angioplasty in acute coronary syndromes without persistent ST-segment elevation improves outcome but increases the need for six-month repeat revascularization: an analysis of the PURSUIT Trial. Platelet glycoprotein IIB/IIIA in Unstable angina: Receptor Suppression Using Integrilin Therapy.

OBJECTIVES: We explored the effect of timing of percutaneous coronary intervention (PCI) in acute coronary syndromes (ACS) without persistent ST-segment elevation on the need for repeat revascularization, and we related this effect to other events. BACKGROUND: Percutaneous coronary intervention is widely used to treat ACS without persistent ST-segment elevation. Moreover, restenosis and subsequent revascularization after PCI are more frequent in ACS than in stable angina. The optimal timing of PCI in ACS without persistent ST-segment elevation is unknown. METHODS: In the Platelet glycoprotein IIB/IIIA in Unstable angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) database, patients were stratified by the time of PCI. In the PURSUIT trial, 9,461 patients received a platelet glycoprotein IIb/IIIa inhibitor, eptifibatide or placebo for 72 h. The investigators decided on other treatments. RESULTS: A total of 2,430 patients underwent PCI within 30 days. Repeat revascularization (during 165 days) was notably higher for PCI within 24 h of enrollment (n = 620 [19%]) than for PCI at 24 to 72 h (n = 624 [16.7%]), 3 to 7 days (n = 614 [13.2%]), or 8 to 30 days (n = 561 [7.7%]; p < 0.001), regardless of eptifibatide use. This gradual reduction in the revascularization rate for later PCI was also observed after multivariate analysis correcting for baseline characteristics and with time as a continuous variable. CONCLUSIONS: Percutaneous coronary intervention within 24 is associated with improved outcome (other analysis) but more repeat revascularization. Prospective analyses are needed to test the hypothesis that rapid PCI in ACS with a platelet glycoprotein IIb/IIIa receptor antagonist reduces myocardial infarction (and possibly death) and is therefore most suited for patients at highest risk of infarction, despite a higher need for repeat revascularization.

Prognostic value of coronary blood flow velocity and myocardial perfusion in intermediate coronary narrowings and multivessel disease.

OBJECTIVES: This study aimed to investigate the roles of intracoronary derived coronary flow velocity reserve (CFVR) and myocardial perfusion scintigraphy (single photon emission computed tomography, or SPECT) for management of an intermediate lesion in patients with multivessel coronary artery disease. BACKGROUND: Evaluation of the functional significance of intermediate coronary narrowings (40% to 70% diameter stenosis) is important for clinical decision making and risk stratification. METHODS: In a prospective, multicenter study, SPECT was performed in 191 patients with stable angina and multivessel disease and scheduled for angioplasty (percutaneous transluminal coronary angioplasty, or PTCA) of a severe coronary narrowing. Coronary flow velocity reserve was determined selectively distal to an intermediate lesion in another artery using a Doppler guidewire. Percutaneous transluminal coronary angioplasty of the intermediate lesion was deferred when SPECT was negative or CFVR greater-than-or-equal 2.0. Patients were followed for one year to document major cardiac events (death, infarction, revascularization), related to the intermediate lesion. RESULTS: Reversible perfusion defects were documented in the area of the intermediate lesion in 30 (16%) patients; CFVR was positive in 46 (24%) patients. Percutaneous transluminal coronary angioplasty of the intermediate lesion was deferred in 182 patients. During follow-up, 19 events occurred (3 myocardial infarctions, 16 revascularizations). Coronary flow velocity reserve was a more accurate predictor of cardiac events than was SPECT; relative risk: CFVR 3.9 (1.7 to 9.1), p < 0.05; SPECT 0.5 (0.1 to 3.2), p = NS. Multivariate analysis revealed CFVR as the only significant predictor for cardiac events. CONCLUSIONS: Deferral of PTCA of intermediate lesions in multivessel disease is safe when CFVR greater-than-or-equal 2.0 (event rate 6%). This selective evaluation of coronary lesion severity during cardiac catheterization allows a more accurate risk stratification than does SPECT, which is important for clinical decision making in this patient cohort.