The following studies were presented at the 11th Annual Symposium on Transcatheter Cardiovascular Therapeutics, September 22–26, 1999, in Washington, DC.
Radiation Therapy for In-Stent Restenosis
The Presenter: Martin Leon, Cardiology Research Foundation, Washington Heart Center, Washington, DC.
The Study: A multicenter, randomized, prospective, placebo-controlled study of radiation therapy for in-stent restenosis. A total of 252 patients with in-stent restenosis in native coronary arteries were randomized to receive adjunctive radiation therapy with an Ir192 gamma source (n=131) or sham placebo treatment (n=121) after percutaneous therapy (at the discretion of the operator). Dosimetry was guided by intraprocedural intravascular ultrasound (IVUS) measurements. All patients received aspirin and ticlopidine for 8 weeks. Follow-up angiography was performed at 6 months, with measurement of both in-lesion and in-stent minimum lumen diameter (MLD). The primary end point of the study was the cumulative incidence of adverse clinical events (death, myocardial infarction [MI], or target lesion revascularization) at 9 months.
Results: More than 80% of the patients received additional adjunctive stents as part of their therapy. In-hospital outcomes were similar between groups. The primary end point was significantly reduced in the radiation therapy group (28.2% versus 43.8% in the sham treatment group); this was largely driven by a dramatic reduction in the need for target vessel revascularization. However, the composite incidence of death or MI tended to be somewhat higher in the radiation therapy group (16% versus 8% in the sham treatment group), and there was a significant increase in the incidence of late stent closure in the radiation therapy group (6.1% versus 0% in the sham treatment group). On qualitative coronary angiography at 6 months, in-stent MLDs were significantly higher in the radiation therapy group; in-lesion MLDs also tended to be higher with radiation. This effect was somewhat more prominent in shorter lesions, and it was very prominent in diabetic patients. There was a suggestion that with larger radiation doses, the reduction in restenosis was more prominent. Approximately one-third of restenosis took place outside the stent. On retrospective analysis of the angiograms, the positioning of the radiation sources was judged to be suboptimal (inadequate longitudinal coverage) in ≈50% of patients.
Conclusions: In patients with in-stent restenosis in a native vessel, radiation therapy with a gamma source is feasible. It results in a substantial improvement in angiographic restenosis and target lesion revascularization more often in shorter lesions and in patients with diabetes. However, there seems to be no benefit of radiation therapy on the composite of death/MI (with a trend actually favoring placebo), and there is a disturbing increase in late stent closure with radiation therapy. Despite careful intraprocedural attention, source placement is suboptimal in ≈50% of cases.
Intravascular Ultrasound-Guided Stent Placement
Angiography Versus Ultrasound-Directed Stent Placement (AVID)
The Presenter: Robert Russo, Scripps Clinic, LaJolla, Calif.
The Study: A randomized, multicenter, parallel-group trial evaluating angiographic versus intravascular ultrasound guidance for coronary stent placement. A total of 800 patients at a low risk for complications who were undergoing elective stent placement in vessels >2.5 mm in which the stent was initially successfully deployed underwent intravascular ultrasound. In 406 of them, only angiographic guidance was used to assess the adequacy of stent deployment; in these patients, the IVUS results were obtained, but they were not used for subsequent clinical decision making. In the remaining 394 of the patients, the adequacy of stent deployment (and subsequent therapies to achieve adequate deployment) was assessed using IVUS criteria (full stent opposition, treated cross-sectional area >90% of distal vessel cross-sectional area, no remaining major dissection). The primary end point of the study was the incidence of target lesion revascularization (TLR) at 12 months.
The Results: Additional therapy (primarily additional balloon inflations) was performed in 1.5% of patients in the angiographically-directed group and in 41.6% of those in the IVUS-directed group. The mean postprocedural MLD of the IVUS group was significantly greater than that of the angiographically-guided group (2.97 versus 2.88 mm; P=0.02). There was a relatively low incidence (≈0.5%) of procedural complications related to the additional therapy in the IVUS-guided group. Interestingly, in ≈58% of cases in the IVUS-guided group, the final IVUS results did not achieve the prespecified criteria for success. For all vessels entered in the study, the primary end point at 12 months (TLR) was slightly, but not significantly, lower in the IVUS-guided group (8.4% versus 12.4% in the angiographically-guided group; P=0.08; 95% confidence intervals, −8.4%, 0.8%). TLR was significantly lower in the IVUS group (4.9% versus 10.8%; P=0.02) when protocol violators (preprocedure reference diameter <2.5 mm) were excluded. In patients undergoing treatment of saphenous vein grafts (n=91), a significant reduction in TLR existed in the IVUS-guided group (5.1% versus 20.8% in the angiographically guided group; P=0.03). Additional subgroups in which IVUS guidance was superior to angiographic guidance included patients with a preprocedural lesion severity of >50%, especially if the lesion was >70% (14.4% versus 3.4% with IVUS guidance; P=0.003), and vessels >2.5 mm.
Summary: Although in the overall population only a nonsignificant trend favored IVUS guidance, the positive results when protocol violators were excluded suggest that IVUS may be of significant benefit in patients with vein graft lesions, more severe stenoses, and vessels <3.5 mm and >2.5 mm.
Other Interventional Studies
Creatine Kinase and Outcome Following Coronary Intervention
The Presenter: Gregg W. Stone, Cardiovascular Research Foundation, Washington Heart Center, Washington, DC.
The Study: A prospective, single-center registry in which creatine kinase (CK)-MB levels (by radioimmunoassay) were determined at baseline, at 8 to 12 hours, and at 16 to 24 hours after elective percutaneous intervention in 7149 consecutive patients. Clinical, procedural, and follow-up data were collected; subsequent adverse clinical events were separately adjudicated. Repeat procedures on the same patient were excluded (to avoid double-counting of long-term outcome events), as were acute or recent MI patients and patients who died or required bypass surgery within 24 hours of the procedure. Stents were implanted in 53% of lesions, and atheroablative procedures were performed in 54% of lesions. The relationship between the degree of CK-MB elevation and long-term outcome was examined, including an analysis of patients with CK-MB elevation, with and without Q-wave MI.
Results: Overall, CK-MB was elevated in 37.3% of patients (>3×upper limits of normal [ULN] in 17.9% of patients; >8×ULN in 7.7%). By logistic regression, elevated CK-MB level was the strongest determinant of in-hospital mortality. The most powerful predictors of late mortality (mean follow-up, 1.4 years) were low left ventricular ejection fraction, advanced age, and peak CK-MB levels. The most striking contribution of CK-MB elevation to mortality was in patients with a Q-wave MI (in-hospital mortality, 25.6%; 1-year mortality, 38.3%) and in patients with CK-MB >8×ULN without Q waves (in-hospital mortality, 3.5%; 1-year mortality, 11.7%). No relationship was found between CK-MB elevation and mortality in patients with CK-MB≤8×ULN and no Q waves (in-hospital mortality, 0.4%; 1-year mortality, 3.4%).
Summary: In this large, single-center registry experience, with a relatively high percentage of stent and atheroablative procedures, CK-MB with Q-wave MI or CK-MB>8×ULN was associated with increased mortality. CK-MB≤8×ULN in the absence of Q waves did not seem to adversely affect in-hospital and 1-year mortality.
Antiplatelet Therapy Versus Lovenox Plus Antiplatelet Therapy for Patients With an Increased Risk for Stent Thrombosis (ATLAST)
The Presenter: James Zidar, Duke University Medical Center, Durham, NC.
The Study: A randomized, multicenter, double-blind, parallel-group trial of enoxaparin (a low-molecular-weight heparin) as an adjunct to conventional anticoagulant therapy in high-risk stent patients. Qualifying patients were randomized to postprocedure therapy with either ticlopidine (for 2 weeks), aspirin (indefinitely), and enoxaparin (60 mg SC every 12 hours for 14 days; dose reduced to 40 mg if patient weighed <65 kg) or ticlopidine/aspirin and placebo injections. Patients receiving glycoprotein IIb/IIIa antagonists were excluded from the study. The primary end point of the study was the 30-day composite of death, MI, or urgent revascularization. The trial was originally designed to include a total of 2000 patients (assuming a 6.5% placebo event rate). However, when a prespecified interim analysis (at 500 patients) showed an overall primary event rate of only 2.5%, the sponsor elected to terminate enrollment in August 1998 rather than expand the sample size. Final adjudicated data were available on 1121 patients. Almost one-half of the implanted stents were Palmaz-Schatz stents.
The Results: The 30-day composite end point was 2.7% in the placebo group (n=549) and 1.8% in the enoxaparin group (n=553); this difference did not achieve statistical significance. At the 6-month follow-up, composite events were 19.8% in the enoxaparin group and 16.6% in the placebo group; this was also a nonsignificant trend. There did seem to be different 30-day outcomes among the different stent designs; they were highest (7.7%) in the GR-I stents (n=52) and lowest (0%) in the Multi-link stents (n=211). Some variability in the effect of enoxaparin among the different stents also seemed to exist (no benefit in GR-I, Palmaz-Schatz, or Multi-link; a suggestion of more prominent benefit in GR-II and other stents). Major bleeding events were slightly, but not significantly, more frequent with enoxaparin (3.3% versus 1.6% with placebo). Minor bleeding events (primarily ecchymosis at the injection site) were more frequent with enoxaparin (25% versus 5% with placebo).
Summary: The 30-day event rates in high-risk stent patients were lower than those previously reported in this trial including latter-generation stent designs. In AT LAST, a 2-week course of subcutaneous enoxaparin was not associated with significant clinical benefit. The potential benefits of adjunctive low-molecular-weight heparin therapy may vary among the various types of stent designs.
Reprint requests to James J. Ferguson, MD, Cardiology Research, MC 1-191, Texas Heart Institute, 1101 Bates St, Houston, TX 77030.
- Copyright © 2000 by American Heart Association