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Dr. James P. Zidar, Duke University Medical Center, Box 3290, Erwin Road, Durham, North Carolina 27710-0001, USA.
The angiography and interventional cardiology working group reviewed 1,095 abstracts for this year’s scientific sessions and accepted 355. There were five areas of major impact from the meeting: the use of distal projection strategies for vein graft intervention and acute myocardial infarction (AMI), new thromboatherectomy devices, the role of inflammation in percutaneous coronary intervention (PCI), new insights on drug-eluting stents, and peripheral interventions.
In the setting of AMI, Drs. Gibson and Stone have previously demonstrated that distal emboli and inflammation in the distal coronary bed predict 30-day and 1-year mortality, even in the presence of Thrombolysis In Myocardial Infarction grade 3 (TIMI-3) flow. Advancing this work, Dr. Limbruno presented the Filter Wire Distal Protection Trial in AMI. This 100-patient study enrolled patients who presented with ST-segment elevation within six hours and <TIMI-3 flow in a native coronary vessel >3 mm. Patients were randomized to stent with or without the protection of the distal filter wire. An improvement in TIMI-3 flow and myocardial blush scores, more rapid resolution of ST-segment changes, and improvement in regional wall motion recovery and less distal emboli were demonstrated in the treated group relative to the control group. Dr. Stone presented the FIRE trial, comparing the Filter Wire to the Percusurge Guard wire in saphenous vein graft (SVG) intervention. This trial was designed as a non-inferiority trial to the approved Guard Wire System. Major adverse cardiac events (MACE) at 30 days with the Filter Wire were equivalent to the Guard Wire, with respect to death, myocardial infarction (MI), and urgent target vessel revascularization.
Data were presented on the X-SIZER catheter, a thromboatherectomy device in AMI. Dr. Reimers and colleagues randomized 92 patients with ST-segment elevation MI and thrombus to the X-SIZER or control. Although there were no differences in TIMI-3 flow, improvements in the more sensitive score of myocardial blush were evident, along with improvements in ST-segment elevation resolution and significant reduction in angiographic complications. There are also trends seen in the recovery of left ventricular function at discharge and at 30 days. These two trials suggest that distal protection offers a beneficial role to our SVG and AMI angioplasty patients.
Inflammation and pci
Turning to inflammation and its role in the angioplasty laboratory, a group at the Cleveland Clinic randomized 75 patients who had elective angioplasty to pretreatment with 300 mg of clopidogrel versus no pretreatment. Dr. Frank Zidar presented data on the inflammatory markers: C-reactive protein, CD-40 ligand, P-selectin, and interleukin-6. Platelet expression was measured directly by flow cytometry. Adenosine diphosphate-activated expression of P-selectin and CD-40 ligand were reduced both pretreatment and immediately post-angioplasty, with recovery back to normal after the first 24 h. These reductions in inflammation may explain part of the beneficial effect of clopidogrel pretreatment in the larger PCI-CURE and CREDO trials.
Perhaps the most interesting trial was ISAR-REACT, presented by Dr. Kastrati, randomizing 2,000 low-risk patients undergoing elective angioplasty to adjunctive treatment abciximab or placebo. Importantly, they pretreated these patients for at least 2 h with a very large dose of Plavix (600 mg/day), twice the standard U.S. loading dose. Importantly, they excluded any high-risk or moderate-risk patients, insulin-requiring diabetics, MI within two weeks, unstable angina, any vein graft intervention, or ejection fraction of <30%. With aggressive pretreatment, there was no difference in death, MI, or the combination of death, MI, or urgent revascularization at 30 days. Major and minor bleeding rates were similar, but an increase in transfusions was noted in the abciximab group. This study suggests that a new antiplatelet strategy may be appropriate in the low-risk, elective angioplasty patient.
Drug-eluting stents (des)
Dr. Bill O’Neill presented the primary end points of the DELIVER trial, randomizing 1,043 U.S. patients to the PENTA or the ACHIEVE stent (the PENTA stent with a non–polymer-based paclitaxel coating). They randomized 1,043 patients. At nine months, there was no difference in death or MI. There was a nonsignificant decrease in target lesion revascularization with the rapid release of this drug-eluting stent (10% reduced to 7%). The primary end point, nine-month target vessel failure (defined as death, MI, or revascularization of the target site) was reduced by 20% but failed to achieve the prespecified 40% reduction. Angiography was performed at baseline and eight months in three-quarters of the patients. In this subgroup analysis, binary restenosis was reduced from 22% to 16.7% with the ACHIEVE stent (p = NS). The control group had lower angiographic and clinical restenosis rates than anticipated, whereas the drug-eluting stent group had higher rates than predicted, resulting in a modest treatment effect. Clearly, this system does reduce the incidence of fibrointimal hyperplasia within stent, but the magnitude of that effect is modest and clearly not what has been demonstrated with other drug-eluting stent trials.
One-year outcomes of the TAXUS II trial were presented by Dr. Antonio Columbo. This European trial tested the polymer-based Boston Scientific paclitaxel NIR stent with a control group and two treatment arms. Six-month outcomes were presented at the TransCatheter Therapeutics meeting 2002. Clopidogrel was prescribed for six months post-PCI. An absolute reduction in major adverse cardiac end points of 8.8% was evident at six months. At 12 months, this benefit increased to 10.5%. Therefore, it appears that paclitaxel, on a polymer-based system with prolonged delivery, appears efficacious and durable. The U.S. interventional community awaits the results of the U.S.-based TAXUS IV data later this year.
Dr. Leon presented a subanalysis of the SIRIUS trial, the sirolimus-eluting BX Velocity stent compared with the uncoated stent. The diabetic subgroup represented 28% of the patients in the 1,000-patient trial. In this high-risk group, sirolimus has much lower angiographic late-loss and restenosis rates than the control group, resulting in significant reductions in target lesion revascularization and MACE events at nine months. However, these results were much less striking for the smaller subgroup of insulin-requiring diabetics. More data are clearly warranted in this challenging population.
Dr. Grube presented the first experience with the everolimus coated S-stent, an analog of sirolimus. This small trial (42 patients) compared the everolimus stent with the bare S stent in a 2:1 randomization scheme. A unique feature of this polymer-based system is the biodegradable delivery on a metal stent. There was only one target lesion revascularization in either group at six months. The angiographic and intravascular ultrasound (IVUS) data were most interesting. An 88% reduction in in-stent late loss (by angiography) and a similar 87% reduction of in-stent plaque volume (by IVUS) were noted in the DES versus control groups.
Dr. David Cohen presented an economic analysis of the SIRIUS trial, an important issue for the interventional community. An incremental increase of $2,000 was assessed for the sirolimus stent versus the control stent. There was a difference in in-hospital costs of approximately $2,800. Most of the cost ($2,500) was recovered in one year as the sirolimus-eluting stent had a reduction in clinical events. At one year, the difference in costs is a modest $300, suggesting a cost-effective strategy with a significant benefit for patients.
In the same American College of Cardiology session, the FACIT trial was presented. The Swiss Heart study suggested folate reduced restenosis by 50%. A group of European investigators led by Dr. Lange randomized 636 patients undergoing elective stenting to placebo or the combination of folate, vitamin B12, and vitamin B6 in the FACIT trial. At six months, the folate group had higher restenosis and major cardiac event rates, questioning the utility of folate in the angioplasty population.
Two presentations at the poster sessions addressed the question of whether oral rapamycin would be an effective alternative to minimize in-stent restenosis. Dr. Mehran’s group gave the rapamycin drug, Rapamune, in two groups of 15 stent patients, with stable or unstable angina and type A or type B1 lesions. After a pretreatment dose of 6 mg, group I received 2 mg/day for two weeks and group II received 2 mg/day for four weeks. Apparently, this dose was reasonably tolerated, except for several aphthous ulcers in group II. Long-term data were only available for group I and revealed an angiographic late loss of 0.48 mm, half the standard 0.8-mm late loss with conventional stents.
Clinical data on a new stent design, the Medtronic DRIVER cobalt-chromium stent, were presented at this meeting by Dr. Michael Sketch. This 300-patient registry assessed outcomes with this thinner strut stent, using a similar design to the S7 stent. Target lesion revascularization at six months was <4%, and target vessel failure was 6.7%. In a 100-patient angiographic subgroup, the binary restenosis rate was 15% and the late loss was 0.91 mm. This new stent designs confer some benefit on angiographic restenosis and clinical outcomes but still suffers from the conventional late loss of ∼0.8 mm.
The ARCHeR trial was presented in the late breaking clinical trials session by Dr. Mark Wholey. This prospective registry assessed outcomes for carotid stenting in a high-risk population for carotid endarterectomy. This multicenter U.S. study required independent neurology assessment before enrollment. At baseline, asymptomatic patients had to have ≥80% stenosis by angiography and symptomatic patients ≥50%. The Guidant ACCULINK stent (made of self-expanding Nitinol available in tapered or non-tapered designs) was used with distal protection (ACCUNET filter). There were 513 patients enrolled in this registry over two years, 476 registry patients, and 76 lead-in patients. Of the high-risk entry criteria, a large percentage had restenosis after carotid endarterectomy, low ejection fraction, heart failure, ≥2-vessel coronary disease, the need for open heart surgery within one month, or occlusion of the contralateral carotid. Placement and delivery of the ACCUNET filter was 93% successful. Debris was seen in 57% of the filters. The composite event rate of death, MI, and stroke was 7.8%, including study-related and non–study-related events, and 5.5% for study-related events. The findings are concurrent with the SAPHIRE data presented at the 2002 American Heart Association annual meeting by Dr. Yadav.
The PARIS trial, presented by Dr. Ron Waxman, randomized 200 patients with SFA disease to primary angioplasty versus angioplasty with brachytherapy using a gamma source, iridium 192. Percutaneous transluminal angioplasty of the SFA is an area fraught with high restenosis rates. They attempted to randomize 300 patients but were only able to enroll 200 patients before the sponsor stopped the study after three years. Repeat angiograms were available for 135 patients. Contrary to most radiation trials, there was no benefit for brachytherapy in this trial. This trial demonstrates the challenges of randomized trials in the peripheral circulation.
New devices have continued to test conventional interventional approaches to common clinical challenges. Adjunctive pharmacologic strategies are evolving (i.e., the clopidogrel dose). Worldwide experience with drug-eluting stents is expanding rapidly. The first drug-eluting stent should be available in the U.S. within the month. Two carotid stent trials have shown favorable data in high-risk patient subsets. These landmark studies should lead to approval and use in the general clinical community within the year.
- American College of Cardiology Foundation