Randomized comparison of GR-II stent and Palmaz-Schatz stent for elective treatment of coronary stenoses.

BACKGROUND: This prospective multicenter randomized clinical trial was designed to evaluate the long-term angiographic and clinical outcomes of elective treatment with the GR-II stent compared with the Palmaz-Schatz (PS) stent in patients with coronary stenoses. METHODS AND RESULTS: Seven hundred fifty-five patients with myocardial ischemia and de novo native coronary stenoses in 3- to 4-mm vessels were randomly assigned to the PS (375 patients) or the GR-II stent (380 patients). The primary end point was 12-month target lesion revascularization (TLR)-free survival. Angiography was performed at baseline and at follow-up in the first 300 consecutive patients to assess the frequency of angiographic restenosis. Procedure success was 98.5% for the GR-II stent and 99.4% for the PS stent (P:=0.19). At 30 days, patients assigned to the GR-II stent had a higher stent thrombosis rate (3.9% versus 0.3% for PS stent, P:<0.001) and TLR rate (3.9% versus 0.5% for PS stent, P:<0.001). The GR-II group had a higher follow-up restenosis frequency (47.3% versus 20.6% for the PS group, P:<0.001) and a lower 12-month TLR-free survival rate (71.7% versus 83.9% for the PS group, P:<0. 001). Multivariate logistic regression analysis identified a smaller final stent minimal lumen diameter (odds ratio [OR] 2.49, 95% CI 1. 56 to 3.98; P:<0.001), diabetes mellitus (OR 2.14, 95% CI 1.42 to 3. 22; P:<0.001), and use of the GR-II stent (OR 1.78, 95% CI 1.20 to 2. 64; P:<0.01) as independent determinants of 12-month TLR. CONCLUSIONS: On the basis of these long-term follow-up data, we conclude that use of the GR-II stent should be limited to the acute treatment of abrupt or threatened closure after failed conventional balloon angioplasty procedures.

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

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

Provisional stenting strategies: systematic overview and implications for clinical decision-making.

Coronary stents reduce the rates of abrupt closure, emergency coronary artery bypass graft surgery and restenosis, but do not prevent myocardial infarction or death at six months. The financial burden of increased stent use and the difficulty in managing in-stent restenosis have provided the impetus to develop provisional stenting strategies. Patients at low risk for restenosis after balloon angioplasty may not derive additional benefit from stent implantation and may be successfully managed with percutaneous transluminal coronary angioplasty (PTCA) alone. Numerous patient, lesion and procedural predictors of restenosis have been identified. Postprocedural assessment using quantitative coronary angiography, intravascular ultrasound (IVUS), coronary flow velocity reserve (CVR) or fractional flow reserve (FFR) may further enhance the ability to predict adverse outcomes after PTCA. Several studies have been performed to investigate the feasibility of provisional stenting strategies using various modalities to identify low risk patients who could be managed with PTCA alone. An optimal or "stent-like" angiographic result after PTCA is associated with favorable clinical outcomes. Preliminary results of studies using IVUS or CVR to guide provisional stenting appear promising. Angiography alone may be inadequate to identify truly low risk patients and may need to be combined with clinical factors, assessment of recoil, IVUS or physiologic indexes. Strategies that avoid unnecessary stenting in even a small proportion of patients may have large impacts on health care costs. Provisional stenting may potentially reduce costs and rates of in-stent restenosis without compromising the quality of health care delivery.

Acute and long-term cost implications of coronary stenting.

OBJECTIVES: We compared the acute and one year medical costs and outcomes of coronary stenting with those for balloon angioplasty (percutaneous transluminal coronary angioplasty) in contemporary clinical practice. BACKGROUND: While coronary stent implantation reduces the need for repeat revascularization, it has been associated with significantly higher acute costs compared with coronary angioplasty. METHODS: We studied patients treated at Duke University between September 1995 and June 1996 who received either coronary stent (n = 384) or coronary angioplasty (n = 159) and met eligibility criteria. Detailed cost data were collected initially and up to one year following the procedure. Our primary analyses compared six and 12 month cumulative costs for coronary angioplasty- and stent-treated cohorts. We also compared treatment costs after excluding nontarget vessel interventions; after limiting analysis to those without prior revascularization; and after risk-adjusting cumulative cost estimates. RESULTS: Baseline clinical characteristics were generally similar between the two treatment groups. The mean in-hospital cost for stent patients was $3,268 higher than for those receiving coronary angioplasty ($14,802 vs. $11,534, p < 0.001). However, stent patients were less likely to be rehospitalized (22% vs. 34%, p = 0.002) or to undergo repeat revascularization (9% vs. 26%, p = 0.001) than coronary angioplasty patients within six months of the procedure. As such, mean cumulative costs at 6 months ($19,598 vs. $19,820, p = 0.18) and one year ($22,140 vs. $22,571, p = 0.26) were similar for the two treatments. Adjusting for baseline predictors of cost and selectively examining target vessel revascularization, or those without prior coronary intervention yielded similar conclusions. CONCLUSIONS: In contemporary practice, coronary stenting provides equivalent or better one-year patient outcomes without increasing cumulative health care costs.

Achieving optimal results with standard balloon angioplasty: can baseline and angiographic variables predict stent-like outcomes?

OBJECTIVES: To predict which patients might not require stent implantation, we identified clinical and angiographic characteristics associated with repeat revascularization after standard balloon angioplasty. BACKGROUND: Stents reduce the risk of repeat revascularization but are costly and may lead to in-stent restenosis, which remains difficult to treat. Identification of patients at low risk for repeat revascularization may allow clinicians to reserve stents for patients most likely to benefit. METHODS: Data from five interventional trials (5,146 patients) were pooled for analysis. We identified patients with optimal angiographic results (final diameter stenosis < or =30% and no dissection) after balloon angioplasty and determined the multivariable predictors of repeat revascularization. RESULTS: Optimal angiographic results were achieved in 18% of patients after angioplasty. The repeat revascularization rate at six months was lower for patients with optimal results (20% vs. 26%, p < 0.001) but still higher than observed in stent trials. Independent predictors of repeat revascularization were female gender (odds ratio [OR] 1.67, p = 0.01), lesion length > or =10 mm (OR 1.62, p = 0.03) and proximal left anterior descending coronary artery lesions (OR 1.62, p = 0.03). For the 8% of patients with optimal angiographic results and none of these risk factors, the repeat revascularization and target vessel revascularization rates were 14% and 8% respectively, similar to rates after stent implantation. Cost analysis estimated that $78 million per year might be saved in the U.S. with a provisional stenting strategy using these criteria compared with elective stenting. CONCLUSIONS: A combination of baseline characteristics and angiographic results can be used to identify a small group of patients at very low risk for repeat revascularization after balloon angioplasty. Provisional stenting for these low risk patients could substantially reduce costs without compromising clinical outcomes.

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

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

Low-molecular-weight heparins in coronary stenting (the ENTICES trial). ENoxaparin and TIClopidine after Elective Stenting.

The role of low-molecular-weight heparins (LMWHs) in the management of stent thrombosis, although expected to produce fewer hemorrhagic complications than warfarin anticoagulation regimens, is poorly defined. The ENoxaparin and TIClopidine after Elective Stenting (ENTICES) trial was designed to compare a combination of a LMWH (enoxaparin), ticlopidine, and aspirin with the conventional warfarin anticoagulant treatment in patients who received coronary stents, in an effort to decrease stent thrombosis and ischemic clinical events. The results show that the enoxaparin regimen produced significantly fewer clinical events and vascular complications than the conventional warfarin anticoagulant regimen.

Treatment of long coronary artery narrowings with long angioplasty balloon catheters.

Balloon angioplasty of long coronary artery narrowings has been associated with a lower rate of acute success, and a higher rate of acute complications and restenosis than that observed for short narrowings. Angioplasty catheters with longer length balloons (30 and 40 mm) are now available, and the objective of this study was to determine the acute and long-term success for patients with long coronary artery narrowings treated with these longer balloons. All patients with long narrowings (> or = 10 mm) treated with long balloons at 1 institution over a 1-year period were identified (93 narrowings in 89 patients), and acute and long-term outcomes were carefully documented. Procedural success (residual stenosis < or = 50%) was 97%. Abrupt closure occurred in 6% and major dissection in 11% of narrowings. Clinical success (procedural success without in-hospital death, bypass surgery or myocardial infarction) was achieved in 90% of patients. Repeat catheterization was performed in 61 patients (76% of those eligible), and restenosis was found in 50 to 55%, depending on the definition used. The treatment of long coronary artery narrowings using angioplasty catheters with longer balloons leads to high rates of acute success. However, there is a high rate of restenosis. New interventional devices for long lesions should be compared with long balloons in a randomized controlled trial.

Outcome after prolonged balloon inflations of greater than 20 minutes for initially unsuccessful percutaneous transluminal coronary angioplasty.

Prolonged balloon inflation with or without autoperfusion techniques is a common initial approach to major dissection or abrupt occlusion after percutaneous transluminal coronary angioplasty (PTCA). To assess such a strategy in the setting of unsuccessful angioplasty, 40 patients who underwent prolonged balloon inflations of greater than 20 minutes between January and July of 1991 after initially unsuccessful angioplasty were studied. These patients (median age 59 years) underwent PTCA for progressive or unstable angina (16[40%]), symptomatic or asymptomatic residual stenosis after myocardial infarction (10[25%]), acute myocardial infarction (3[8%]), stable angina (3[8%]), reinfarction (2[5%]), and other indications (6[15%]). The significant stenoses were primarily in the proximal and midportions of the right coronary (53%), left anterior descending (30%) and left circumflex (17%) coronary arteries. Before prolonged balloon inflation, the longest single inflation was 11 +/- 6 minutes and the total time of all inflations was 17 +/- 8 minutes (mean +/- standard deviation). Stenosis was reduced from 91 +/- 9 to 68 +/- 16% before prolonged inflation. After prolonged balloon inflation of 30 +/- 9 minutes, the residual stenosis was 47 +/- 21% (p = 0.0001 vs value before prolonged inflation). Furthermore, improvements in the appearance of filling defects or dissections, or both, occurred in 19 patients (48%). Procedural success was obtained in 32 of 40 patients (80%). Coronary bypass grafting was performed in 8 patients (20%): 4 after unsuccessful PTCA (3 emergently) and 4 electively after initially successful PTCA. Although 5 patients had creatine kinase-MB elevations greater than 20 IU/liter after the procedure, only 1 sustained a Q-wave myocardial infarction. There were no deaths in the hospital.(ABSTRACT TRUNCATED AT 250 WORDS)

Diagnosing coronary arterial stent thrombosis and arterial closure.

This single-center review of a consecutive series of patients requiring reexamination by angiography within 1 week of a coronary stent placement due to chest pain reveals that patients treated with a poststent anticoagulation regimen of warfarin and aspirin, and those with lower poststent deployment dilation pressures, have an increased risk of subacute stent thrombosis. Repeat cardiac catheterization within the first week after coronary artery stent implantation should be reserved for patients with significant electrocardiographic changes.

Outcomes following interventions in small coronary arteries with the use of hand-crimped Palmaz-Schatz stents.

Although coronary stenting has been shown to be effective, retrospective studies have suggested that stents do not provide better results than angioplasty in small coronary arteries. We sought to examine procedural, in-hospital, and long-term outcomes of patients undergoing small-vessel stenting with Palmaz-Schatz stents hand-crimped on a balloon catheter <3 mm in diameter. We retrospectively analyzed the outcomes of 117 patients who underwent this type of coronary stent implantation at Duke University Medical Center between January 1, 1997 and May 30, 1998. The clinical indications for percutaneous revascularization included unstable angina in 67.5% of patients, acute myocardial infarction in 4.3%, postinfarct angina in 3.4%, silent ischemia in 3.4%, and stable angina in 1% of patients. Quantitative angiographic analysis was performed immediately before angioplasty and after stent implantation. Stents were used for elective indications in 24%, for suboptimal angiographic result in 61.5%, and for abrupt and/or threatened closure in 14.5% of patients. Reference vessel diameter was similar before and after the procedure. Minimum luminal diameter increased from 0.63 to 2.35 mm, an acute gain of 1.72+/-0.43 mm. Percent stenosis decreased from 74.2% to 4.7%. The clinical composite of death (n = 1, 1%), nonfatal myocardial infarction (n = 6, 5.1%), and revascularization (n = 1, 1%) occurred in-hospital in only 8 patients (6.8%), resulting in clinical procedure success in 109 patients (93%). Our data suggest that stents designed for vessels >3.0 mm can be deployed in small vessels, with a low in-hospital event rate. However, target lesion revascularization in small vessels remains high. Development of antiproliferative strategies could improve long-term outcomes for small-vessel interventions.

Local administration of L-703,081 using a composite polymeric stent reduces platelet deposition in canine coronary arteries.

We compared the effect on platelet deposition of the glycoprotein IIb/IIIa receptor antagonist L-703,081, administered locally via a drug delivery stent, with that of a standard metal stent in a canine coronary model. There was a significant reduction in platelet deposition using the L-703,081-impregnated stent compared with the bare metal stent. This study demonstrates an alternative route of delivery of GPIIb/IIIa antagonists with potential advantages over systemic administration.

Current status of biodegradable stents.

Coronary angioplasty remains limited by abrupt closure and restenosis. Metallic stents are useful for suboptimal PTCA results or threatened closure and can reduce restenosis in de novo lesions. However, they are permanent devices that are used to treat a short-term problem and have only limited potential for local drug delivery. Several catheters have been designed for specific delivery of drugs or gene products. Unfortunately drug delivery efficiency and long-term retention remain problematic. To overcome these limitations and provide a scaffold for the remodeling vessel as well as a vehicle for sustained local drug delivery, bioabsorbed stents have been proposed as an alternative. This article describes the limitations of the current metallic stents, reviews the initial animal studies of polymeric stents, and proposes the biodegradable stent as a local drug delivery device to prevent restenosis and acute closure post-PTCA.

Low molecular weight heparin in coronary stenting.

A pilot clinical study called Enoxaparin and Ticlopidine after Elective Stenting (ENTICES) was designed to determine whether the combination of enoxaparin, ticlopidine and acetylsalicylic acid (ASA) is superior to the conventional five-drug regimen routinely used after elective stent placement (warfarin, unfractionated heparin, dextran, dipyridamole and ASA). Compared with patients on conventional therapy (44), those randomly assigned to enoxaparin and ticlopidine (79) had a lower composite rate of in-hospital bleeding and vascular complications (5% versus 16%; P = 0.005), a significantly lower composite end-point rate (death, nonfatal myocardial infarction, stent thrombosis of urgent revascularization) at 30 days (5% versus 20%; P = 0.001), a significantly lower incidence of stent thrombosis in the first 30 days (0% versus 7%; P = 0.04) and the same incidence of death or repeat angioplasty at six months. The Antiplatelet Therapy versus Lovenox plus Antiplatelet Therapy for Patients with an Increased Risk of Stent Thrombosis (ATLAST) trial was subsequently designed to compare the efficacy of the combination therapy enoxaparin. ASA and ticlopidine with that of antiplatelet therapy alone after coronary stent placement in patients at increased risk of stent thrombosis. Target enrolment of 2000 patients began in December 1996 and is expected to be complete by the end of 1998. In summary, the ENTICES pilot study demonstrated that the low molecular weight heparin enoxaparin is safe and effective for use with ASA and ticlopidine for elective stent patients. The ATLAST trial should provide results on whether enoxaparin is beneficial in patients at high risk for stent thrombosis.

Rationale for low-molecular weight heparin in coronary stenting.

Stents have been as revolutionary for the practice of coronary revascularization in recent years as was the coronary angioplasty balloon 15 years ago, but they have also been associated with a high rate of stent thrombosis. The Enoxaparin and Ticlopidine After Elective Stenting (ENTICES) trial is designed to determine the impact of a reduced anticoagulation regimen on clinical outcomes after stent deployment. Patients are randomly assigned 2:1 to enoxaparin-ticlopidine-aspirin versus the conventional warfarin regimen, and surrogate markers of platelet activation and thrombin activity are measured after 3 days. Three factors underpin ENTICES: (1) a desire to eliminate stent thrombosis, (2) a desire to reduce length of stay after stent placement by avoiding the prolonged hospitalization required with the five-drug regimen of heparin, aspirin, dipyridamole, dextran, and warfarin, and (3) a desire to reduce the bleeding complications associated with the intense anticoagulation typically used in patients receiving stents. Patients are enrolled at seven sites in the United States and include patients with recent infarctions, restenotic lesions, and lesions as large as 30 mm in length. Other trials have also addressed issues concerning anticoagulation in patients undergoing stenting. The Stent Antithrombotic Regimen Study (STARS) trial compared aspirin, aspirin plus ticlopidine, and aspirin plus warfarin in 1650 patients receiving stents. The Aspirin/Ticlopidine vs Low-Molecular Weight Heparin/Aspirin/Ticlopidine High-Risk Stent Trial (ATLAST) is comparing aspirin plus ticlopidine with enoxaparin, aspirin, and ticlopidine in a group of patients at high risk undergoing stenting. The Intracoronary Stenting and Antithrombotic Regimen (ISAR) trial, a trial of ticlopidine, aspirin, and 12 hours of postprocedural heparin versus phenocoumaron on and aspirin after stenting in 517 patients, found a significantly lower incidence of the combined end point of death, myocardial infarction, bypass surgery, or repeated percutaneous transluminal angioplasty in the patients who received antiplatelet therapy, but the patients enrolled were not representative of the usual population undergoing stenting. New trials of stents and their sequelae should include low-molecular weight heparins and should gather cost and outcome data to satisfy capitated systems and managed care. Innovative stent designs may also permit changes in antithrombotic regimens.

The use of intraaortic balloon counterpulsation in acute myocardial infarction and high risk coronary angioplasty.

Patients with complex coronary arterial stenoses, decreased ejection fraction, or acute myocardial infarction are at increased risk during percutaneous coronary interventions. Intraaortic balloon counterpulsation (IABP) can provide benefit in such cases by several mechanisms. Myocardial perfusion is improved and left ventricular afterload is reduced by balloon counterpulsation. Patients with cardiogenic shock clearly benefit from balloon counterpulsation until revascularization can be performed. Recent studies have documented the utility of balloon counterpulsation in patients undergoing angioplasty as treatment for an acute myocardial infarction. Balloon counterpulsation is also an effective means to reduce ischemia and provide hemodynamic support during complex percutaneous coronary interventions. This review will summarize the benefits, indications, and complications of balloon counterpulsation during acute myocardial infarction and high-risk coronary angioplasty.